Randomized phase III trial of single versus fractionated thoracic radiation in the palliation of patients with lung cancer (NCIC CTG SC.15). A Phase III Randomized Trial of Combined Chemoradiotherapy Versus Radiotherapy Alone in Locally Advanced Non–Small-Cell Lung Cancer Inoperable non-small-cell lung cancer (NSCLC): a Medical Research Council randomised trial of palliative radiotherapy with two fractions or ten fractions. Report to the Medical Research Council by its Lung Cancer Working Party. Randomized phase III trial of sequential chemoradiotherapy compared with concurrent chemoradiotherapy in locally advanced non-small-cell lung cancer: Groupe Lyon-Saint-Etienne d'Oncologie Thoracique-Groupe Français de Pneumo-Cancérologie NPC 95-01 Study. Phase I study of vinorelbine, cisplatin, and concomitant thoracic radiation in the treatment of advanced chest malignancies. Continuously infused carboplatin used as radiosensitizer in locally unresectable non-small-cell lung cancer: a multicenter phase III study. Quality of life of inoperable non-small cell lung carcinoma. A randomized phase II clinical study comparing radiotherapy alone and combined radio-chemotherapy. Concurrent versus sequential chemoradiotherapy with cisplatin and vinorelbine in locally advanced non-small cell lung cancer: a randomized study. Randomized phase II study of cisplatin with gemcitabine or paclitaxel or vinorelbine as induction chemotherapy followed by concomitant chemoradiotherapy for stage IIIB non-small-cell lung cancer: cancer and leukemia group B study 9431. A prospective, randomised study to compare two palliative radiotherapy schedules for non-small-cell lung cancer (NSCLC) Concurrent cisplatin, etoposide, and chest radiotherapy in pathologic stage IIIB non-small-cell lung cancer: a Southwest Oncology Group phase II study, SWOG 9019. Palliative radiation for stage 3 non-small cell lung cancer--a prospective study of two moderately high dose regimens. Mitomycin, ifosfamide, and cisplatin in unresectable non-small-cell lung cancer: effects on survival and quality of life. Randomized trial of thoracic irradiation plus combination chemotherapy for unresectable adenocarcinoma and large cell carcinoma of the lung. Palliative radiotherapy for lung cancer: two versus five fractions. A randomized study on palliative radiation therapy for inoperable non small cell carcinoma of the lung. Results of the Dutch National study of the palliative effect of irradiation using two different treatment schemes for non-small-cell lung cancer. A Medical Research Council (MRC) randomised trial of palliative radiotherapy with two fractions or a single fraction in patients with inoperable non-small-cell lung cancer (NSCLC) and poor performance status. Medical Research Council Lung Cancer Working Party. Standard thoracic radiotherapy with or without concurrent daily low-dose carboplatin in elderly patients with locally advanced non-small cell lung cancer: a phase III trial of the Japan Clinical Oncology Group (JCOG9812). Combined chemoradiotherapy regimens of paclitaxel and carboplatin for locally advanced non-small-cell lung cancer: a randomized phase II locally advanced multi-modality protocol. Results of combination chemotherapy and thoracic radiation therapy for unresectable non-small cell carcinoma of the lung. A randomized clinical trial comparing radiation therapy v radiation therapy plus cis-dichlorodiammine platinum (II) in the treatment of locally advanced non-small cell lung cancer. Impact of irradiation technique and tumor extent in tumor control and survival of patients with unresectable non‐oat cell carcinoma of the lung. Report by the radiation therapy oncology group Radiosensitization with carboplatin for patients with unresectable stage III non-small-cell lung cancer: a phase III trial of the Cancer and Leukemia Group B and the Eastern Cooperative Oncology Group. A randomised clinical trial of radiotherapy plus cisplatin versus radiotherapy alone in stage III non-small cell lung cancer. Hyperfractionated radiation therapy with or without concurrent low-dose daily carboplatin/etoposide for stage III non-small-cell lung cancer: a randomized study. Immediate versus delayed palliative thoracic radiotherapy in patients with unresectable locally advanced non-small cell lung cancer and minimal thoracic symptoms: randomised controlled trial Hyperfractionated radiation therapy and concurrent low-dose, daily carboplatin/etoposide with or without weekend carboplatin/etoposide chemotherapy in stage III non-small-cell lung cancer: a randomized trial. The possible advantage of hyperfractionated thoracic radiotherapy in the treatment of locally advanced nonsmall cell lung carcinoma Chemotherapy/radiation therapy plus/minus lonidamine in the treatment of non-small cell lung cancer (limited disease): preliminary results. Preliminary results of radiotherapy with or without weekly paclitaxel in locally advanced non-small cell lung cancer Hypofractionated palliative radiotherapy (17 Gy per two fractions) in advanced non-small-cell lung carcinoma is comparable to standard fractionation for symptom control and survival: a national phase III trial. Randomized trial of hyperfractionated radiation therapy with or without concurrent chemotherapy for stage III non-small-cell lung cancer. A randomised phase III study of accelerated or standard fraction radiotherapy with or without concurrent carboplatin in inoperable non-small cell lung cancer: final report of an Australian multi-centre trial. Randomized phase II study of induction chemotherapy with gemcitabine plus cisplatin followed by sequential radiotherapy versus radiotherapy alone in patients with stage III non-small cell lung cancer. Effects of concomitant cisplatin and radiotherapy on inoperable non-small-cell lung cancer. A randomized study of high-dose split course radiotherapy preceded by high-dose chemotherapy versus high-dose radiotherapy only in locally advanced non-small-cell lung cancer. An EORTC Lung Cancer Cooperative Group trial. A feasibility study of extended chemotherapy for locally advanced non-small cell lung cancer: a phase II trial of cancer and leukemia group B. Phase III study of concurrent versus sequential thoracic radiotherapy in combination with mitomycin, vindesine, and cisplatin in unresectable stage III non-small-cell lung cancer. Induction chemotherapy followed by concomitant chemoradiotherapy (CT/XRT) versus CT/XRT alone for regionally advanced unresectable non-small cell lung cancer (NSCLC): Initial analysis of a randomized phase III trial. Improved survival in stage III non-small-cell lung cancer: seven-year follow-up of cancer and leukemia group B (CALGB) 8433 trial. Sequential chemoradiotherapy versus radiotherapy in the management of locally advanced non-small-cell lung cancer Consolidation docetaxel after concurrent chemoradiotherapy in stage IIIB non-small-cell lung cancer: phase II Southwest Oncology Group Study S9504. Induction chemoradiation and surgical resection for non-small cell lung carcinomas of the superior sulcus: Initial results of Southwest Oncology Group Trial 9416 (Intergroup Trial 0160). Comparison of induction chemotherapy before radiotherapy with radiotherapy only in patients with locally advanced squamous cell carcinoma of the lung. The Swedish Lung Cancer Study Group. Why are missing quality of life data a problem in clinical trials of cancer therapy? Randomized trial of palliative two-fraction versus more intensive 13-fraction radiotherapy for patients with inoperable non-small cell lung cancer and good performance status. Medical Research Council Lung Cancer Working Party.
PURPOSE This multi-institutional Phase III r and omized study compared 10 Gy single-fraction radiotherapy ( RT ) with 20 Gy in five fractions in the palliation of thoracic symptoms from lung cancer . METHODS AND MATERIAL S The primary end point was palliation of thoracic symptoms at 1 month after RT , evaluated by a patient-completed daily diary card . Secondary end points included quality of life , toxicity , and survival . RESULTS Most ( 69 % ) of 230 patients r and omized had locally advanced disease unsuitable for curative treatment . The treatment arms were well balanced with respect to the known prognostic factors . At 1 month after RT , no difference was found in symptom control between the two arms , as judged by the daily diary scores . The changes in the scores on the Lung Cancer Symptom Scale indicated that the fractionated RT ( five fractions ) group had greater improvement in symptoms related to lung cancer ( p = 0.009 ) , pain ( p = 0.0008 ) , ability to carry out normal activities ( p = 0.037 ) , and better global quality of life ( p = 0.039 ) . The European Organization for Research and Treatment of Cancer QLQ-C30 scores showed that patients receiving five fractions had a greater improvement in scores with respect to pain ( p = 0.04 ) . No significant difference was found in treatment-related toxicity . Patients who received five fractions survived on average 2 months longer ( p = 0.0305 ) than patients who received one fraction . CONCLUSION Although the two treatment strategies provided a similar degree of palliation of thoracic symptoms , the difference in survival between the two study arms was of a clinical ly relevant magnitude A phase III r and omized trial was conducted to investigate whether induction chemotherapy followed by radiation can influence survival as compared with radiation alone in unresectable , locally advanced non-small-cell lung cancer ( LADNSCLC ) . A total of 101 patients with unresectable stage IIIA or IIIB NSCLC were enrolled . Patients were stratified by performance status , weight loss , histology and stage , and then r and omized to receive combined chemoradiotherapy or radiotherapy alone . Radiotherapy was administered in 1.8 Gy to 2.0 Gy st and ard fractions daily 5 times weekly for a total dose of 60 Gy to 65 Gy . The combined group received induction of cisplatin , etoposide , and vinblastine ( PEV ) chemotherapy with cisplatin 20 mg/m2 on days 1 to 5 , etoposide 100 mg/m2 on days 2 to 4 , and vinblastine 6 mg/m2 on day 1 , which wasrepeated every 3 weeks for 3 courses , after which time the patients underwent radiotherapy .  Of 101 patients registered , 89 patients ( 43 combined , 46 radiotherapy alone ) were eligible for analysis . The response rates for the combined and radiotherapy groups were 65 % ( 28/43 ) and 70 % ( 32/46 ) , respectively . The median survival time ( MST ) showed a tendency to be more prolonged in the combined group than in the group receiving radiotherapy alone ( 13.8 vs. 8.5 months ) . The MST in patients with nonsquamous histology was strikingly prolonged in the combined group as compared with the radiotherapy group ( 14 vs. 3.6 months , p 0.027 ) . Likewise , the MST in patients with stage IIIB was significantly prolonged in the combined group as compared with the radiotherapy group ( 11.1 vs. 7.2 months , p 0.045 ) . Together , the MST of the high-risk group with nonsquamous or stage IIIB was significantly higher in the combined group than that seen in the radiotherapy group ( 11.6 vs. 8 months , p 0.046 ) , whereas the MST of the low-risk group , defined as having both squamous histology and stage IIIA , was similar in the two treatment groups ( 18.3 vs. 20.8 months , p = 0.293 ) . In conclusion , induction PEV chemotherapy plus radiotherapy is superior to radiotherapy alone in high-risk subsets of unresectable LAD-NSCLC and therapeutic strategy should be based on the identification of prognostic factors Two policies of palliative thoracic radiotherapy for non-small-cell lung cancer have been compared in a r and omised multicentre controlled trial . A total of 369 patients with inoperable , histologically or cytologically confirmed disease , too advanced for radical ' curative ' radiotherapy , and with their main symptoms related to the primary intrathoracic tumour even if metastases were present , were studied . They were allocated at r and om either to a regimen of 17 Gy given in two fractions of 8.5 Gy 1 week apart ( F2 regimen ) , or to a conventional multifractionated regimen of either 30 Gy in ten fractions or 27 Gy in six fractions ( a biologically equivalent dose ) , given daily except at weekends ( FM regimen ) . On admission , 93 % of the patients had cough , 47 % haemoptysis , 57 % chest pain , 58 % anorexia  , and 11 %  dysphagia . As assessed by the clinicians , palliation of the main symptoms was achieved in high proportions of patients ranging in the F2 group from 65 % for cough to 81 % for haemoptysis and in the FM group from 56 % for cough to 86 % for haemoptysis . Haemoptysis , chest pain , and anorexia disappeared for a time in well over half the patients with these symptoms , and cough in 37 % . For all the main symptoms , the median duration of palliation was 50 % or more of survival . Performance status improved in approximately half of the patients with a poor status on admission . All these results were similar in the two treatment groups . As assessed daily by the patients using a diary card , the quality of life deteriorated slightly during treatment but then improved steadily during the next 5 weeks . The proportion of patients with dysphagia increased considerably during treatment , but fell to the pretreatment level during the next 2 weeks . The results were similar in the two groups . Radiation myelopathy was suspected in one ( F2 ) patient . There was no difference in survival between the two groups ( log-rank test ) , the median survival time from the date of allocation being 179 days in the F2 and 177 days in the FM group . In the light of all the findings , the regimen of two fractions of 8.5 Gy given 1 week apart is recommended PURPOSE We conducted a phase III study to compare the survival impact of concurrent versus sequential treatment with radiotherapy ( RT ) and chemotherapy ( CT ) in unresectable stage III non-small-cell lung cancer ( NSCLC ) . PATIENTS AND METHODS Patients were r and omly assigned to one of the two treatment arms . In the sequential arm , patients received induction CT with cisplatin ( 120 mg/m2 ) on days 1 , 29 , and 57 , and vinorelbine ( 30 mg/m2/wk ) from day 1 to day 78 , followed by thoracic RT at a dose of 66 Gy in 33 fractions ( 2 Gy per fraction and 5 fractions per week ) . In the concurrent arm , the same RT was started on day 1 with two concurrent cycles of cisplatin 20 mg/m2/d and etoposide 50 mg/m2/d ( days 1 to 5 and days 29 to 33 ) ; patients then received consolidation therapy with cisplatin 80 mg/m2 on days 78 and 106 and vinorelbine 30 mg/m2/wk from days 78 to 127 . RESULTS Two hundred five patients were r and omly assigned . Pretreatment characteristics were well balanced between the two arms . There were six toxic deaths in the sequential arm and 10 in the concurrent arm . Median survival was 14.5 months in the sequential arm and 16.3 months in the concurrent arm ( log-rank test P = .24 ) . Two- , 3- , and 4-year survival rates were better in the concurrent arm ( 39 % , 25 % , and 21 % , respectively ) than in the sequential arm ( 26 % , 19 % , and 14 % , respectively ) . Esophageal toxicity was significantly more frequent in the concurrent arm than in the sequential arm ( 32 % v 3 % ) . CONCLUSION Although not statistically significant , clinical ly important differences in the median , 2- , 3- , and 4-year survival rates were observed , with a trend in favor of concurrent chemoradiation therapy , suggesting that is the optimal strategy for patients with locally advanced NSCLC PURPOSE The cisplatin-vinorelbine regimen has superior activity in advanced non-small-cell lung cancer ( NSCLC ) . We conducted a phase I trial to identify the maximum-tolerated dose ( MTD ) and dose-limiting toxicities ( DLTs ) of this regimen with concomitant thoracic radiation ( RT ) in patients with advanced chest malignancies . PATIENTS AND METHODS Patients with advanced chest malignancies that required RT were enrolled onto this phase I study of st and ard chest radiation ( 30 daily 2-Gy fractions for a total of 60 Gy ) and concurrent chemotherapy with cisplatin starting at 100 mg/m2 every 3 weeks and vinorelbine starting at 20 mg/m2/wk . RESULTS Thirty-seven patients were treated on this study . Two of three patients treated at the maximum-administered dose of cisplatin 100 mg/m2 per cycle and vinorelbine 25 mg/m2/wk experienced acute DLT ( neutropenia ) , which required deescalation . The dose level of cisplatin 100 mg/m2 and vinorelbine 20 mg/m2/wk , although tolerated acutely , produced delayed esophagitis , which proved dose-limiting . The recommended phase II dose was cisplatin 80 mg/m2 every 3 weeks and vinorelbine 15 mg/m2 given 2 of every 3 weeks with concomitant chest RT . CONCLUSION Concomitant chemoradiotherapy with cisplatin and vinorelbine is feasible . The recommended phase II dose is cisplatin 80 mg/m2 every 3 weeks with vinorelbine 15 mg/m2 given twice over 3 weeks on a day 1/day 8 schedule . Esophagitis is the DLT , with neutropenia occurring at higher dose levels . A Cancer and Leukemia Group B ( CALGB ) phase II trial is currently underway to evaluate further the efficacy and toxicities of this regimen in unresectable stage III NSCLC PURPOSE To determine the radiosensitizing effect of prolonged exposure of carboplatin in patients with locally unresectable non-small-cell lung cancer ( NSCLC ) . PATIENTS AND METHODS Patients with histologically proven NSCLC , performance score < 2 , weight loss < 10 % , and normal organ functions were r and omized between carboplatin 840 mg/m2 administered continuously during 6 weeks of radiotherapy or thoracic radiotherapy alone ( both 60 Gy ) . Toxicity was evaluated with National Cancer Institute Common Toxicity Criteria ( NCI CTC ) and the Radiation Therapy Oncology Group ( RTOG ) criteria . Quality of life was measured with European Organization for Research and Treatment of Cancer ( EORTC ) QLQ-C30/LC13 question naires . RESULTS One-hundred and sixty patients were included . Pathologically confirmed persistent tumor was present in 53 % of patients in the combination arm versus 58 % in the radiotherapy alone arm ( P=0.5 ) . Median survival in the combination arm was 11.8 [ 95 % confidence interval ( CI ) 9.3 - 14.2 ] months and in the radiotherapy alone arm 11.7 ( 95 % CI 8.1 - 15.5 ) months ; progression-free survival was not different between arms [ 6.8 and 7.5 months , respectively ( P=0.28 ) ] . Acute toxicity was mild , late toxicity was radiation-induced cardiomyopathy ( three patients ) and pulmonary fibrosis ( five patients ) . Quality of life was not different between arms , but in all measured patients cough and dyspnea improved , pain became less , and slight paresthesia developed 3 months after treatment . CONCLUSION Addition of continuously administered carboplatin as radiosensitizer for locally unresectable NSCLC does not improve local tumor control or overall survival Eighty one patients with inoperable non-small cell lung carcinoma ( NSCLC ) were entered in a r and omized phase II trial comparing split-dose irradiation alone to combined treatment radiotherapy and polychemotherapy ( C.A.P. + V.D.S. ) . The quality of life and the survival of the patients were studied . We have defined three classes of quality of life responses based on the time elapsed before the performance status index drops . A higher quality of life failure rate was observed in the combined treatment group ( p non-significant ) but the time elapsed before the Karnofsky index drops is longer in the combined treatment group for the quality of life " no change " subgroup ( p = 0.15 ) . Survival and quality adjusted survival are similar in both treatment groups . The same conclusion holds for retrospective stratified treatment groups . The results of the study are presented according to the decision tree theory . We conclude that as far as the quality of life is concerned , polychemotherapy combined with the particular split-dose irradiation schedule used is an effective treatment of inoperable NSCLC . Its efficiency is comparable to , but not better than , the same radiotherapy schedule alone taken as a reference baseline PURPOSE The superiority of chemoradiotherapy ( CRT ) over radiation alone in locally advanced non-small cell lung cancer ( NSCLC ) has been proven , but the relative merits of a concurrent schedule versus their sequential administration are less clear . This study compared the safety and efficacy of concurrent and sequential CRT , with chemotherapy ( CT ) consisting of a cisplatin and vinorelbine regimen , in patients with locally advanced NSCLC . PATIENTS AND METHODS One hundred and two previously untreated patients ( aged 42 - 75 years ) with locally advanced , stage IIIA ( n = 15 ) or stage IIIB ( n = 87 ) NSCLC were entered into the study . The CT schedule consisted of up to four cycles of cisplatin 80 mg/m(2 ) on day 1 , and vinorelbine 25 mg/m(2 ) at the first and fourth cycles ( 12.5 mg/m(2 ) during the 2nd/3rd cycles ) on days 1 , 8 , 15 of a 28-day cycle . Radiotherapy ( RT ) was prescribed at a dose of 60 Gy/30 fractions , given as five fractions per week for 6 weeks . In the concurrent arm ( arm A ) , RT was started on day 4 of cycle 2 ; whilst in the sequential arm ( arm B ) , RT started within 2 weeks after completion of CT . Fifty-two patients were r and omized to concurrent treatment and 50 to the sequential schedule . RESULTS Overall survival was significantly longer in arm A ( median survival 16.6 months ) versus arm B ( median survival 12.9 months ) ( P = 0.023 by means of log-rank test ; hazard ratio HR = 0.61 , 95 % CI of HR ( 0.39 - 0.93 ) ) , and time to progression ( TTP ) was also significantly longer in arm A ( median time to progression 11.9 months ) versus arm B ( median time to progression 8.5 months ) ( P = 0.024 by means of log-rank test ; HR = 0.62 , 95 % CI of HR ( 0.38 - 0.93 ) ) . Ninety-eight patients were evaluable for response and 101 for toxicity .  The overall response rate was significantly higher in arm A , 80 % ( with 21 % complete response ( CR ) ) compared with 47 % ( with 17 % CR ) in arm B ( P = 0.001 by means of chi(2)-test ) . WHO grade 3 or 4 toxicity was more frequent in arm A than in arm B , with a significantly greater incidence of leucopenia ( 53 % versus 19 % , P = 0.009 by means of chi(2 ) test ) and nausea/vomiting ( 39 % versus 15 % , P = 0.044 by means of chi(2 ) test ) . There were no treatment related deaths . CONCLUSION In this study population , concurrent CRT demonstrated significant benefit in terms of response rate , overall survival and time to progression over sequential CRT . The concurrent CRT schedule was associated with higher toxicity ; however , the adverse event profile was acceptable in both arms PURPOSE To evaluate new drugs in combination with cisplatin in unresectable stage III non-small-cell lung cancer , Cancer and Leukemia Group B ( CALGB ) conducted a r and omized phase II study of two cycles of induction chemotherapy followed by two additional cycles of the same drugs with concomitant radiotherapy . PATIENTS AND METHODS Eligible patients received four cycles of cisplatin at 80 mg/m(2 ) on days 1 , 22 , 43 , and 64 with arm 1 : gemcitabine 1,250 mg/m(2 ) on days 1 , 8 , 22 , and 29 and 600 mg/m(2 ) on days 43 , 50 , 64 , and 71 ; arm 2 : paclitaxel 225 mg/m(2 ) for 3 hours on days 1 and 22 and 135 mg/m(2 ) on days 43 and 64 ; and arm 3 : vinorelbine 25 mg/m(2 ) on days 1 , 8 , 15 , 22 , and 29 and 15 mg/m(2 ) on days 43 , 50 , 64 , and 71 . Radiotherapy was initiated on day 43 at 2 Gy/d ( total dose , 66 Gy ) . RESULTS One hundred seventy-five eligible patients were analyzed . Toxicities during induction chemotherapy consisted primarily of grade 3 or 4 granulocytopenia . Grade 3 or 4 toxicities during concomitant chemoradiotherapy consisted of thrombocytopenia , granulo-cytopenia , and esophagitis . Response rates after completion of radiotherapy were 74 % , 67 % , and 73 % for arms 1 , 2 , and 3 , respectively . Median survival for all patients was 17 months . One- , 2- , and 3-year survival rates for the patients on the three arms were 68%/37%/28 % , 62%/29%/19 % , and 65%/40%/23 % . CONCLUSION Four cycles of gemcitabine , vinorelbine , or paclitaxel in combination with cisplatin can be administered at these doses and schedules . The observed survival rates exceed those of previous CALGB trials and may be attributable to the use of concomitant chemoradiotherapy . Induction chemotherapy added to concomitant chemoradiotherapy is being evaluated in a phase III r and omized trial A prospect i ve r and omised study compared two palliative radiotherapy schedules for inoperable symptomatic non-small-cell lung cancer ( NSCLC ) . After stratification , 100 patients were r and omly assigned to 20 Gy/5 fractions (fr)/5 days ( arm A ) or 16 Gy/2 fr/day 1 and 8 ( arm B ) . There were 90 men and 10 women aged 47–81 years ( mean 66 ) , performance status 1–4 ( median 2 ) . The major clinical characteristics and incidence and degree of initial disease-related symptoms were similar in both groups . Treatment effects were assessed using patient 's chart , doctor 's scoring of symptomatic change and chest X-ray . Study end points included degree and duration of symptomatic relief , treatment side effects , objective response rates and overall survival . A total of 55 patients were assigned to arm A and 45 to arm B. In all , 98 patients received assigned treatment , whereas two patients died before its termination . Treatment tolerance was good and did not differ between study arms . No significant differences between study arms were observed in the degree of relief of all analysed symptoms . Overall survival time differed significantly in favour of arm B ( median 8.0 vs 5.3 months ; P=0.016 ) . Both irradiation schedules provided comparable , effective palliation of tumour-related symptoms . The improved overall survival and treatment convenience of 2-fraction schedule suggest its usefulness in the routine management of symptomatic inoperable NSCLC PURPOSE There are no published survival data after chemoradiotherapy ( chemoRT ) in pathologically documented stage IIIB non-small-cell lung cancer . Studies of radiotherapy ( RT ) alone or chemotherapy followed by RT yield 5-year survivals less than 10 % . The Southwest Oncology Group ( SWOG ) employed the same concurrent chemoRT induction regimen used in its predecessor trimodality trial to determine the efficacy , safety , and long-term outcome of replacing postinduction surgery with additional chemoRT . PATIENTS AND METHODS Eligible patients for SWOG-9019 had pathologic documentation of T4N0/1 , T4N2 , or N3 stage IIIB non-small-cell lung cancer . They had pulmonary function adequate to withst and combined-modality therapy , identical to the requirements of the previous trial with postchemoRT surgery . Induction therapy was two cycles of cisplatin plus etoposide ( PE ) concurrent with once-daily thoracic RT ( 45 Gy ) . In the absence of progressive disease , RT was completed to 61 Gy , with two additional cycles of cisplatin plus etoposide . RESULTS Fifty eligible patients were accrued with tumor-node ( TN ) substage confirmed on central review : 18 , T4N0/1 ; 12 , T4N2 ; and 20 , N3 . Grade 4 neutropenia was the most common toxicity ( 32 % ) . Grade 3/4 esophagitis occurred in 12 % and 8 % . Median follow-up was 52 months , and overall median survival was 15 months ( 10 to 22 , 95 % confidence interval ) . Three- and 5-year survivals were 17 % and 15 % ( 5-year T4N0/1 , 17 % ; T4N2 , 13 % ; and N3 , 15 % ) . CONCLUSION Feasibility and long-term survival support the application of these results as a st and ard against which mature outcomes of chemoRT trials with new chemotherapy agents can be compared . These results also justify use of the SWOG-9019 approach as a control arm in ongoing phase III trials Eighty four patients from Groote Schuur Hospital and Frere Hospital East London were entered into a prospect i ve r and omised trial between January 1990 and December 1993 . All the patients possessed non-small cell carcinoma ( NSCLC ) of the lung too extensive for radical irradiation and World Health Organization performance status 0 - 2 . The patients were r and omised to receive either 35 Gy in 10 fractions ( 43 patients ) or 45 Gy in 15 fractions ( 41 patients ) . In the patients treated to 35 Gy and 45 Gy , the median survival was 8.5 months in both groups , the symptomatic response rate was 68 % and 76 % and the incidence of moderate to severe radiation oesophagitis was 23 % and 41 % respectively . The latter approached statistical significance ( P = 0.07 , chi square ) . There was no evidence of a dose response effect on survival in the moderate dose range in patients treated palliatively for locally advanced NSCLC PURPOSE Chemotherapy for non-small-cell lung cancer ( NSCLC ) remains controversial . We describe the two largest reported , r and omized , parallel trials design ed to determine whether the addition of chemotherapy influences duration and quality of life in localized , unresectable ( mitomycin , ifosfamide ,  cisplatin [MIC]1 trial ) and extensive ( MIC2 trial ) disease . PATIENTS AND METHODS Ambulatory patients with NSCLC , aged 75 years or younger , with localized disease , were r and omized in MIC1 to receive up to four cycles of chemotherapy ( CT : mitomycin 6 mg/m(2 ) , ifosfamide 3 g/m(2 ) , and cisplatin 50 mg/m(2 ) ) every 21 days , followed by radical radiotherapy ( CT + RT ) or radiotherapy ( RT ) alone . Extensive-stage patients were r and omized in MIC2 to identical chemotherapy plus palliative care ( CT + PC ) or palliative care ( PC ) alone . Short-term change in quality of life ( QOL ) was assessed in a subgroup of patients . Data from the two trials were combined to allow multivariate and stratified survival analyses . RESULTS Seven hundred ninety-seven eligible patients were r and omized , 446 in MIC1 and 351 in MIC2 . MIC CT improved survival in both trials ( significantly in MIC2 ) . The median survival time in MIC1 was 11.7 months ( CT + RT ) versus 9.7 months ( RT alone ) ( P = .14 ) ; whereas in MIC2 , median survival time was 6.7 months ( CT + PC ) compared with 4 . 8 months ( PC alone ) ( P = .03 ) . QOL , assessed in 134 patients from start of trial to week 6 , showed improvement with chemotherapy and deterioration with st and ard treatment . In the combined analysis of 797 r and omized patients , the positive effect of MIC on survival was significant overall ( P = .01 ) and after adjusting for prognostic factors ( P = .01 ) . CONCLUSION MIC chemotherapy prolongs survival in unresectable NSCLC without compromising QOL Sixty-eight evaluable patients with unresectable adenocarcinoma and large cell carcinoma of the lung were treated on a prospect i ve r and omized trial comparing thoracic radiation therapy ( TRT ) plus combination chemotherapy with either cyclophosphamide , Adriamycin and cis-platinum ( CAP ) or cyclophosphamide , Adriamycin ( same dosages ) and DTIC ( CAD ) , 34 on each arm . Patients treated with TRT plus CAP had a better overall regression rate ( 59 % vs 47 % ) and a statistically significant superiority in time to disease progression ( 147 days vs 303 days ) and survival ( 217 days vs 504 days ) The aim of this prospect i ve r and omized trial was to compare the symptomatic effects of two different regimens of palliative radiotherapy for lung cancer . Two hundred and sixteen patients needing palliation were r and omized to receive either a 17 Gy mid-point dose in two fractions 1 week apart or 22.5 Gy in five daily fractions . Both toxicity and efficacy were evaluated by postal question naires . This small study was intended to identify any clinical ly important differences in toxicity or efficacy between the two regimens . We detected no such difference , although there was a tendency for iatrogenic dysphagia and improvement in chest pain and cough to be more common with the two-fraction regimen . The only symptom that was improved in over 50 % of patients for 8 weeks or more was haemoptysis . Haemoptysis and chest pain appeared to be the best indications for treatment . The relief of other symptoms was disappointing in both degree and duration Between October 1981 and November 1984 , 291 patients with inoperable advanced non-small cell carcinoma of the lung ( NSCLC ) were r and omized to a two-arm study . Eighteen of 291 defaulted treatment and were excluded from the study . Twenty-seven of 273 died during treatment ; they were invaluable for treatment response but were included in survival analysis . Without correction for lung attenuation 45 Gy/18 fractions/4 1/2 weeks were given in arm 1 and 31.2 Gy/4 fractions/4 weeks were given in arm 2 . One hundred twenty-eight of 273 were included in arm 1 and 145/273 in arm 2 . The two arms were comparable in patient age , sex , performance status and symptoms , primary tumor site , histology , stage of the disease , and distribution of metastases and radiation portal size used . Prognosis was poor with an overall median survival of 20 weeks and was similar in both arms . Radiological tumor response was also similar : 53 % in arm 1 and 50 % in arm 2 . However arm 1 was superior than arm 2 in achieving symptom palliation , 71 % vs 54 % , p less than 0.02 . Treatment complications were mild and included mainly radiation oesophagitis and pneumonitis and pulmonary fibrosis . Treatments in both arms were equally well tolerated PURPOSE A national multicenter r and omized study compared the efficacy of 2 x 8 Gy versus our st and ard 10 x 3 Gy in patients with inoperable stage IIIA/B ( with an Eastern Cooperative Oncology Group score of 3 to 4 and /or substantial weight loss ) and stage IV non-small-cell lung cancer . PATIENTS AND METHODS Between January 1999 and June 2002 , 297 patients were eligible and r and omized to receive either 10 x 3 Gy or 2 x 8 Gy by external-beam irradiation .  The primary end point was a patient-assessed score of treatment effect on seven thoracic symptoms using an adapted Rotterdam Symptom Checklist . Study sample size was determined based on an average total symptom score difference of more than one point over the initial 39 weeks post-treatment . The time course of symptom scores were also evaluated , and other secondary end points were toxicity and survival . RESULTS Both treatment arms were equally effective , as the average total symptom score over the initial 39 weeks did not differ . However , the pattern in time of these scores differed significantly ( P < .001 ) . Palliation in the 10 x 3-Gy arm was more prolonged ( until week 22 ) with less worsening symptoms than in 2 x 8-Gy . Survival in the 10 x 3-Gy arm was significantly ( P = .03 ) better than in the 2 x 8-Gy arm with 1-year survival of 19.6 % ( 95%CI , 14.1 % to 27.3 % ) v 10.9 % ( 95%CI , 6.9 % to 17.3 % ) . CONCLUSION The 10 x 3-Gy radiotherapy schedule is preferred over the 2 x 8-Gy schedule for palliative treatment , as it improves survival and results in a longer duration of the palliative response Two policies of palliative thoracic radiotherapy for NSCLC have been compared in a r and omised multicentre controlled trial aim ed at simplifying the palliative treatment of patients with poor performance status . A total of 235 patients were entered . They had inoperable , microscopically confirmed disease , too advanced for ' curative ' radiotherapy . Their main symptoms were related to the primary intrathoracic tumour even if metastases were present , and they had a poor performance status . Patients were allocated at r and om to regimens of either 17 Gy given in two fractions of 8.5 Gy 1 week apart ( F2 regimen , 117 patients ) , or a single fraction of 10 Gy ( F1 regimen , 118 patients ) . Two patients ( one in each group ) were excluded from all analyses because they were found to have had previously treated malignant disease and had been admitted in error . On admission , 95 % of the 233 eligible patients had cough , 47 % haemoptysis , 59 % chest pain , 64 % anorexia , and 16 % dysphagia . As assessed by the clinicians , these symptoms were palliated in high proportions of patients , ranging in the F2 group from 48 % for cough to 75 % for haemoptysis , and in the F1 group from 55 % for anorexia to 72 % for haemoptysis and chest pain . For all five symptoms the median duration of palliation was 50 % or more of survival . All these results were similar in the two treatment groups . In contrast , on daily assessment by the patients using a diary card , those treated with the F2 regimen experienced substantially more dysphagia , which was recorded in 56 % of the patients compared with 23 % in the F1 group ( difference 33 % : 95 % confidence interval 17 - 48 % ) . The median survival from r and omisation was 100 days in the F2 group and 122 days in the F1 group . The F1 regimen , as it requires only a single attendance for treatment , is recommended as a palliative regimen for patients with inoperable NSCLC and a poor performance status BACKGROUND The purpose of this study was to evaluate whether radiotherapy with carboplatin would result in longer survival than radiotherapy alone in elderly patients with unresectable stage III non-small cell lung cancer ( NSCLC ) . METHODS Eligible patients were 71 years of age or older with unresectable stage III NSCLC . Patients were r and omly assigned to the radiotherapy alone ( RT ) arm , irradiation with 60 Gy ; or the chemoradiotherapy ( CRT ) arm , the same radiotherapy and additional concurrent use of carboplatin 30 mg/m(2 ) per fraction up to the first 20 fractions . RESULTS This study was terminated early when 46 patients were registered from November 1999 to February 2001 . Four patients ( one in the RT arm , three in the CRT arm ) were considered to have died due to treatment-related causes . The JCOG Radiotherapy Committee assessed these treatment-related deaths ( TRDs ) and the compliance with radiotherapy in this trial . They found that 60 % of the cases corresponded to protocol deviation and 7 % were protocol violation in dose constraint to the normal lung , two of whom died due to radiation pneumonitis . As to the effectiveness for the 46 patients enrolled , the median survival time was 428 days [ 95 % confidence interval ( CI ) = 212 - 680 days ] in the RT arm versus 554 days ( 95 % CI = 331 to not estimable ) in the CRT arm . CONCLUSIONS Due to the early termination of this study , the effectiveness of concurrent use of carboplatin remains unclear . We re-planned and started a study with an active quality control program which was developed by the JCOG Radiotherapy Committee PURPOSE This phase II noncomparative r and omized trial was conducted to determine the optimal sequencing and integration of paclitaxel/carboplatin with st and ard daily thoracic radiation therapy ( TRT ) , in patients with locally advanced unresected stage III non-small-cell lung cancer ( NSCLC ) . Survival data were compared with historical st and ard sequential chemoradiotherapy data from the Radiation Therapy Oncology Group . PATIENTS AND METHODS Patients with unresected stages IIIA and IIIB NSCLC , with Karnofsky performance status > or = 70 % and weight loss < or = 10 % , received two cycles of induction paclitaxel ( 200 mg/m2)/carboplatin ( area under the plasma concentration time curve [ AUC ] = 6 ) followed by TRT 63.0 Gy ( arm 1 , sequential ) or two cycles of induction paclitaxel ( 200 mg/m2)/carboplatin ( AUC = 6 ) followed by weekly paclitaxel ( 45 mg/m2)/carboplatin ( AUC = 2 ) with concurrent TRT 63.0 Gy ( arm 2 , induction/concurrent ) , or weekly paclitaxel ( 45 mg/m2)/carboplatin ( AUC = 2)/TRT ( 63.0 Gy ) followed by two cycles of paclitaxel ( 200 mg/m2)/carboplatin ( AUC = 6 ; arm 3 , concurrent/consolidation ) . RESULTS With a median follow-up time of 39.6 months , median overall survival was 13.0 , 12.7 , and 16.3 months for arms 1 , 2 , and 3 , respectively . During induction chemotherapy , grade 3/4 granulocytopenia occurred in 32 % and 38 % of patients on study arms 1 and 2 , respectively . The most common locoregional grade 3/4 toxicity during and after TRT was esophagitis , which was more pronounced with the administration of concurrent chemoradiotherapy on study arms 2 and 3 ( 19 % and 28 % , respectively ) . CONCLUSION Concurrent weekly paclitaxel , carboplatin , and TRT followed by consolidation seems to be associated with the best outcome , although this schedule was associated with greater toxicity From October 1979 to December 1982 , 126 patients with locally advanced unresectable or inoperable Stage II ( 7 patients ) , Stage IIIA ( 81 patients ) , and Stage IIIB ( 38 patients ) non-small cell carcinoma of the lung were treated in a prospect i ve r and omized trial using five cycles of CAP ( Cytoxan , Adriamycin , and cisplatin ) , T-CAP ( triazinate plus CAP ) , or V-CAP ( VP-16 plus CAP ) chemotherapy with thoracic radiation therapy ( TRT ) . TRT consisted of 40 Gy in 10 fractions ( split-course ) with cycles 3 and 4 of chemotherapy . The treatment field included the primary tumor , ipsilateral hilum , mediastinum , and ipsilateral supraclavicular fossa . All patients were followed until death or for a minimum of 5 years for survivors . The evaluable subgroup consisted of 102 patients who completed TRT .  Median and 5-year survivals for the entire group were 14.0 months and 10 % , respectively ; for the evaluable subgroup , they were 14.8 months and 12 % , respectively . There was a trend toward better survival with V-CAP plus TRT than with CAP plus TRT ( p = 0.08 ) . Median and 5-year survivals were 16.2 months and 18 % , respectively , with V-CAP plus TRT . Of eight prognostic variables analyzed for their association with survival , only Eastern Cooperative Oncology Group performance status ( 0,1 versus 2 ) ( p = 0.02 ) and weight loss ( less than or equal to 10 % versus greater than 10 % ) ( p = 0.05 ) were significant . Sex , age , T stage , N stage , overall stage , and histologic type were not significantly associated with survival . Failure analysis revealed 83 patients ( 81 % ) with identifiable first failures . The median time to first failure was 9.8 months , and the median survival after first failure was 4.7 months . Failure patterns included local failure alone ( 19 % ) , local and distant ( 20 % ) , and distant alone ( 43 % ) . Nineteen percent of patients had no documented progression . Total failure patterns were local in 39 % and distant in 63 % . Twenty-three patients ( 23 % ) had failure in the brain ; they accounted for 31 % of all distant failures . In 20 of these patients ( 20 % of all patients ) , this was the only site of failure . There were eight ( 8 % ) initial nodal failures in 96 untreated contralateral supraclavicular fossae . No initial failures were seen in any of 101 untreated contralateral hila . The data suggest the following : ( a ) Combined treatment with V-CAP and TRT yielded excellent results ( median survival , 16.2 months ; 5-year survival , 18 % ) . ( ABSTRACT TRUNCATED AT 400 WORDS Cis-Dichlorodiammine platinum ( II ) ( cis-DDP ) was demonstrated to be a potentiator of radiation therapy ( RT ) in experimental tumor models and in cultured cells . To assess the effectiveness of a combined modality treatment including RT and a weekly low-dose administration of cis-DDP , from January 1986 to June 1987 , 95 patients with unresectable locally advanced non-small cell carcinoma of the lung ( stage IIIa , b ) were r and omized for study . Fifty patients received RT alone at doses of 50 Gy ; 45 patients received the same RT plus cis-DDP 15 mg/m2 IV weekly . An overall response rate of 50 % and 64 % was observed in the RT and RT + cis-DDP group , respectively . No statistically significant differences were detected with regard to median survival time ( 11 months for RT v 16 months for RT + cis-DDP ) and progression-free interval ( 7 months in the RT arm v 9 months in the RT + cis-DDP arm ) , but the patterns of the first failure appeared to be affected by treatment . In fact , a lower number of intrathoracic relapses was observed in the RT + cis-DDP arm ( 12 in the RT + cis-DDP v 23 in the RT arm ) . Toxicity was mild and the feasibility of this schedule must be remarked . A better local control of disease can be obtained using cis-DDP as a radiation potentiator , but the true influence of this combined modality treatment on the length of survival , and the optimal cis-DDP timing and dosage are still to be evaluated in further clinical trials An analysis of intrathoracic tumor control was carried out in 378 patients with histologically proven unresectable non‐oat cell carcinoma of the lung treated with definitive radiotherapy , r and omized to one of four treatment regimens :  4000 rad split course ( 2000 rad in five fractions in one week , two weeks rest and additional 2000 rad in five fractions in one week ) or 4000 , 5000 or 6000 rad continuous courses , five fractions per week . Between 85 and 101 patients are analyzed in each treatment group .  The complete plus partial response was 46–51 % in the 4000 rad groups in contrast to 61–66 % in the 5000 to 6000 rad groups ( P = 0.008 ) . The overall two year survival rate was 10–11 % for the patients treated with 4000 rad split or continuous course , and 19 % in the patients treated with 5000 to 6000 rad . The complete response in patients with tumors 3 cm or less in diameter was 16 % when treated with 4000 rad in contrast to 20–31 % in those treated with 5000–6000 rad . In the patients with lesions from 4 to 6 cm in diameter , complete and partial tumor regression was 48 % in the 4000 rad group , 67 % with 5000 rad , and 71 % with 6000 rad . These differences are statistically significant ( P = 0.033 ) . Intrathoracic recurrences were correlated with the dose of irradiation given : 52 % with 4000 rad , 41 % with 5000 rad , and 30 % with 6000 rad ( P = 0.006 ) . An analysis of protocol compliance was carried out in 301 patients with available data , irradiated at the primary site according to protocol instruction ( none or minor variation ) . Median survival for patients treated to the ipsilateral or contralateral hilar lymph nodes according to the protocol varied from 46–50 weeks in contrast to 20–30 weeks for those with major protocol variations in nodal irradiation . Variations in ipsilateral and contralateral nodal irradiation correlated with significant reductions in tumor control ( P = 0.02 and P = 0.009 , respectively ) . In addition to patient and tumor characteristics , the technical factors of irradiation are critical parameters that affect tumor control and survival in patients with non‐oat cell bronchogenic carcinoma . Strict quality assurance criteria in radiotherapy are necessary to achieve optimal treatment results and a careful program to evaluate techniques of irradiation and protocol compliance should be maintained in cooperative group studies in order to enhance the validity of clinical trials PURPOSE To determine whether the administration of carboplatin concurrently with radiation treatment improves survival in patients with inoperable stage III non-small-cell lung cancer . PATIENTS AND METHODS Two hundred eighty-three patients with inoperable stage III non-small-cell lung cancer were entered onto a r and omized trial by the Cancer and Leukemia Group B and the Eastern Cooperative Oncology Group . R and omization was performed before initiation of any therapy . All patients received an induction chemotherapy program with vinblastine and cisplatin for 5 weeks , followed by 6,000 cGy of radiation therapy over 6 weeks . One hundred thirty-seven patients were r and omized to this therapy regimen alone ; 146 patients were r and omized to receive carboplatin at 100 mg/m2/wk concurrent with the radiation therapy . RESULTS The complete response was 18 % with concurrent carboplatin versus 10 % with radiotherapy alone ( P = .101 ) . There was no difference with respect to failure-free survival ( 10 % with carboplatin and 9 % with radiotherapy alone ) or overall survival ( 13 % with carboplatin and 10 % with radiotherapy alone ) at 4 years . In patients not receiving carboplatin , the relapse rate was 69 % within the field of radiation and 53 % in the boost volume . In patients receiving carboplatin , the relapse rate was 59 % within the field of radiation and 43 % in the boost volume . Patients with cancers more than 70 cm2 in size had significantly poorer survival ( P = .01 ) . CONCLUSION Carboplatin at the dose and schedule used did not significantly impact on disease control or survival . The relapse rate within the chest remained more than 50 % . More effective regimens will be required to impact on local disease control and survival This study was design ed to compare high-dose fractionated radiotherapy alone versus the same radiotherapy plus cisplatin in stage III non-small cell lung cancer ( NSCLC ) . We r and omly assigned 176 patients with stage III non-small cell lung cancer to one of two treatments ; fractionated radiotherapy alone at dose of 64 Gy for 6 - 7 weeks ( 2 Gy given 32 times , in five fractions a week ) or radiotherapy in the same schedule , combined with 20mg/m2 cisplatin 1 h before radiotherapy , given on days 1 - 5 of the second and sixth treatment weeks . The frequency of loco-regional progression was 68 % among the patients who received radiotherapy plus cisplatin and 86 % among those who received radiotherapy alone ( P = 0.0001 ) . The probability of survival free of disease after 3 years was 10 % among the patients assigned to radiotherapy plus cisplatin and 0 % among those treated only with radiotherapy ( P = 0.0006 ) . Overall survival at 3 years was 10 % among those given radiotherapy plus cisplatin and 2 % among those who received radiotherapy alone ( P = 0.00001 ) . Multivariate analysis demonstrated that radiotherapy plus cisplatin significantly improved loco-regional progression-free survival and overall survival , irrespective of radiation dose . The addition of cisplatin to fractionated radiotherapy prolongs loco-regional progression-free interval and survival in stage III non-small cell lung cancer PURPOSE To investigate the efficacy of concurrent hyperfractionated radiation therapy ( HFX RT ) and low-dose daily chemotherapy ( CHT ) in stage III non-small-cell lung cancer ( NSCLC ) . PATIENTS AND METHODS Between January 1990 and December 1991 , 131 patients with histologically or cytologically confirmed stage III NSCLC , Karnofsky performance status ( KPS ) > or = 50 , and no previous therapy were r and omly treated as follows : group I , HFX RT with 1.2 Gy twice daily to a total dose of 69.6 Gy ( n = 66 ) ; and group II , same HFX RT with CHT consisting of 50 mg of carboplatin ( CBDCA ) and 50 mg of etoposide ( VP-16 ) given on each RT day ( n = 65 ) . RESULTS Group II patients had a significantly longer survival time than group I patients , with a median survival of 22 versus 14 months and 4-year survival rates of 23 % versus 9 % ( P = .021 ) . The median time to local recurrence and 4-year local recurrence-free survival rate were also significantly higher in group II than in group I ( 25 v 20 months and 42 % v 19 % respectively , P = .015 ) . In contrast , the distant metastasis-free survival rate did not significantly differ in the two groups ( P = .33 ) . The two groups showed similar incidence of acute and late high- grade toxicity ( P = .44 and .75 , respectively ) . No treatment-related toxicity was observed . CONCLUSION The combination of HFX RT and low-dose daily CBDCA plus VP-16 was tolerable and improved the survival of patients with stage III NSCLC as a result of improved local control Abstract Objective : To determine whether patients with locally advanced non-small cell lung cancer unsuitable for resection or radical radiotherapy , and with minimal thoracic symptoms , should be given palliative thoracic radiotherapy immediately or as needed to treat symptoms . Design : Multicentre r and omised controlled trial . Setting : 23 centres in the United Kingdom , Irel and , and South Africa . Participants : 230 patients with previously untreated , non-small cell lung cancer that is locally too advanced for resection or radical radiotherapy with curative intent , with minimal thoracic symptoms , and with no indication for immediate thoracic radiotherapy .  Interventions : All patients were given supportive treatment and were r and omised to receive palliative thoracic radiotherapy either immediately or delayed until needed to treat symptoms . The recommended regimens were 17 Gy in two fractions one week apart or 10 Gy as a single dose . Main outcome measures : Primary — patients alive and without moderate or severe cough , chest pain , haemoptysis , or dyspnoea six months  from r and omisation , as recorded by clinicians . Secondary — quality of life , adverse events , survival . Results : From December 1992 to May 1999 , 230 patients were r and omised . 104/115 of the patients in the immediate treatment group received thoracic radiotherapy ( 90 received one of the recommended regimens ) . In the delayed treatment group , 48/115 ( 42 % ) patients received  thoracic radiotherapy  ( 29 received one of the recommended regimens ) ; 64 ( 56 % ) died without receiving thoracic radiotherapy ; the remaining three ( 3 % ) were alive at the end of the study without having received the treatment . For patients who received thoracic radiotherapy , the median time to start was 15 days in the immediate treatment group and 125 days in the delayed treatment group . The primary outcome measure was achieved in 28 % of the immediate treatment group and 26 % of patients from the delayed treatment group ( 27/97 and 27/103 , respectively ; absolute difference 1.6 % , 95 % confidence interval -10.7 % to 13.9 % ) . No evidence of a difference was observed between the two treatment groups in terms of activity level , anxiety , depression , and psychological distress , as recorded by the patients . Adverse events were more common in the immediate treatment group . Neither group had a survival advantage ( hazard ratio 0.95 , 0.73to 1.24 ; P=0.71 ) . Median survival was 8.3 months and 7.9 months , and the survival rates were 31 % and 29 % at 12 months , for the immediate and delayed treatment groups , respectively . Conclusion : In minimally symptomatic patients with locally advanced non-small cell lung cancer , no persuasive evidence was found to indicate that giving immediate palliative thoracic radiotherapy improves symptom control , quality of life , or survival when compared with delaying until symptoms require treatment PURPOSE To investigate whether the addition of weekend chemotherapy consisting of carboplatin/etoposide to hyperfractionated radiation therapy ( Hfx RT ) and concurrent daily carboplatin/etoposide offers an advantage over the same Hfx RT/daily carboplatin/etoposide . METHODS AND MATERIAL S A total of 195 patients ( Group I , 98 ; Group II , 97 ) were treated with either Hfx RT to a total tumor dose of 69.6 Gy via 1.2 Gy b.i.d . fractionation and daily 50 mg each of carboplatin and etoposide during the RT course ( Group I ) or the same Hfx RT with daily carboplatin/etoposide consisting of 30 mg each of carboplatin and etoposide and with weekend ( Saturdays and Sundays ) 100 mg each of carboplatin and etoposide during the RT course ( Group II ) . RESULTS No difference was found regarding median survival time and 5-year survival rates ( 20 vs. 22 months and 20 % vs. 23 % ; p = 0.57 ) . Median time to local progression was 20 and 19 months , respectively , while 5-year local progression-free survival rates were 28 % and 27 % , respectively ( p = 0.66 ) . Also , there was no difference regarding either median time to distant metastasis and 5-year distant metastasis-free survival ( 21 vs. 25 months and 29 % vs. 34 % , p = 0.29 ) . There was no difference in the incidence of various nonhematologic toxicities between the two treatment groups , but patients treated with the weekend CHT had significantly more high- grade ( > or = 3 ) hematologic toxicity ( p = 0.0046 ) . Late high- grade toxicity was not different between the two treatment groups . CONCLUSION The addition of weekend carboplatin/etoposide did not improve results over those obtained with Hfx RT and concurrent low-dose , daily carboplatin/etoposide , but it led to a higher incidence of acute high- grade hematologic toxicity A three‐arm Phase III r and omized trial was performed to compare response rates , time to local or distant progression , and survival for patients with unresectable ( Stage IIIA or IIIB ) nonsmall cell lung carcinoma treated with st and ard fractionated thoracic radiotherapy ( SFTRT ) versus accelerated hyperfractionated thoracic radiotherapy ( AHTRT ) with or without combination etoposide and cisplatin chemotherapy One hundred sixteen patients with unresectable locally advanced non-small cell lung cancer ( NSCLC ) were accrued in a prospect i ve r and omized trial comparing ( A ) , chemotherapy ( cisplatin and etoposide [ VP-16 ] ) for two courses plus radiation therapy ( 30 + 20 Gy split course ) , followed by an additional two courses to ( B ) , the same regimen plus the addition of lonidamine ( LND ) . There were 93 patients evaluable for response ( 46 in the chemotherapy/radiation arm and 47 in the chemotherapy/radiation/LND arm ) . One hundred fifteen patients were evaluable for toxicity .  The overall response rates , median time to progression , and median survival time were similar in both arms . For the group of patients with squamous cell histology , time to progression was 27 weeks on arm A and 38 weeks on arm B ( P = 0.01 ) . Two-year survival in the squamous cell group in arm A was 9 % , in arm B , 39 % . LND does not give rise to additional toxicity , although myalgia and testicular pain are characteristic side effects Purpose . In this study our objective was to evaluate the therapeutic significance of concurrent paclitaxel and radiotherapy compared with radiotherapy alone . Patients and methods . Patients with stage III A/B NSCLC were r and omly assigned to receive either radiotherapy alone ( group 2 ) or concurrent weekly paclitaxel with radiotherapy ( group 1 ) in GMMA . Radiotherapy was given as a split-course schedule with the total dose of 56 Gy . Paclitaxel , 60 mg/m2 , was administered only to group 1 on the first day of each radiotherapy week . To assess differences between values , P values were calculated with the χ2 test . A Mann Whitney U-test was used to assess significant differences between the two values . Actuarial survival curves were calculated by the Kaplan-Meier method . Results . There were 25 patients who underwent chemoradiotherapy and 26 who underwent radiotherapy only . Median follow-up was 14 months . The overall response rate was 92 % and 70 % for groups 1 and 2 , respectively ( P= 0.003 ) . Median survival was 15.2 months for group 1 , and 12.0 months for group 2 ( P= 0.027 ) . Conclusion . Based on this response and the toxicity profile , outpatient split-course radiotherapy and weekly paclitaxel seems to be feasible and safe PURPOSE To investigate whether the effect of hypofractionated thoracic radiotherapy ( TRT ) is comparable to more st and ard fractionated radiotherapy ( RT ) in advanced non-small-cell lung cancer ( NSCLC ) . PATIENTS AND METHODS A total of 421 patients with locally advanced stage III or stage IV NSCLC tumors were included . Inclusion criteria were inoperable , disease too advanced for curative radiotherapy , and chest symptoms or central tumor threatening the airways . Patients were r and omly assigned to three arms : A , 17 Gy per two fractions ( n = 146 ) ; B , 42 Gy per 15 fractions ( n = 145 ) ; and C , 50 Gy per 25 fractions ( n = 130 ) . Four hundred seven patients were eligible for the study ; 395 patients ( 97 % ) participated in the health-related quality -of-life ( HRQOL ) study . The European Organization for Research and Treatment of Cancer ( EORTC ) Quality of Life Question naire (QLQ)-C30 and EORTC QLQ-lung cancer-specific module ( LC13 ) were used to investigate airway symptom relief and changes in HRQOL . Assessment s were performed before TRT and until week 54 . Clinicians ' assessment s of symptom improvement were at 2 , 6 , and 14 weeks after completion of TRT . The patients were observed for a minimum of 3 years . Results Baseline prognostic data were equally distributed in the treatment groups . Patient compliance with respect to the HRQOL investigation was minimum 74 % . HRQOL and symptom relief were equivalent in the treatment arms . No significant difference in survival among arms A , B , and C was found , with median survival 8.2 , 7.0 , and 6.8 months , respectively . CONCLUSION Our data indicate that protracted palliative TRT renders no improvement in symptom relief , HRQOL , or survival when compared with short-term hypofractionated treatment in advanced NSCLC PURPOSE To investigate the efficacy of combined hyperfractionated radiation therapy ( HFX RT ) and concurrent chemotherapy ( CHT ) in stage IIIA or IIIB non-small-cell lung cancer ( NSCLC ) compared with that of HFX RT alone . PATIENTS AND METHODS Between January 1988 and December 1989 , 169 patients were divided r and omly into the following groups : group I , HFX RT with 1.2 Gy twice daily to a total dose of 64.8 Gy ( n = 61 ) ; group II , same HFX RT with CHT consisting of 100 mg of carboplatin ( CBDCA ) on days 1 and 2 and 100 mg of etoposide ( VP-16 ) on days 1 to 3 of each week during the RT course ( n = 52 ) ; and group III , same HFX RT with CHT consisting of 200 mg of CBDCA on days 1 and 2 and 100 mg of VP-16 on days 1 to 5 of the first , third , and fifth weeks of the RT course ( n = 56 ) . RESULTS The median survival time ( MST ) was 8 months for group I , 18 months for group II , and 13 months for group III . The 3-year survival rates were 6.6 % , 23 % , and 16 % , respectively . There was a significant difference in the survival rate between groups I and II ( P = .0027 , log-rank test ) , but not between groups I and III ( P = .17 ) or between groups II and III ( P = .14 ) . The relapse-free survival rate in group II was also higher than that in group I ( P = .0024 ) , which was largely due to improved local control in group II patients . Patients in groups II and III showed a higher incidence of acute and /or late high- grade toxicity compared with group I patients , but no patient died of treatment-related toxicity . CONCLUSION The combination of HFX RT and continuous CBDCA/VP-16 CHT was tolerable and substantially increased the survival rate PURPOSE To investigate the effects separately and together of ( a ) shortening overall treatment time and ( b ) giving concurrent carboplatin in patients having radical radiotherapy for inoperable non-small-cell lung cancer ( NSCLC ) . PATIENTS AND METHODS Between April 1989 and May 1995 , 204 patients with medically inoperable or technically unresectable NSCLC localised to the primary site and regional lymph nodes were r and omised to receive one of four treatments using a 2 x 2 factorial design : st and ard radiotherapy , 60 Gy in 30 fractions in 6 weeks ( R6 ) ; accelerated radiotherapy , 60 Gy in 30 fractions in 3 weeks ( R3 ) ; st and ard radiotherapy as in R6 with carboplatin 70 mg/m2/day for 5 days during weeks 1 and 5 of radiotherapy ( R6C ) ; accelerated radiotherapy as in R3 with carboplatin 70 mg/m2/day for 5 days during week 1 of radiotherapy ( R3C ) . RESULTS The estimated median survival of all r and omised patients was 15.7 months and estimated 2-year survival was 31 % . The longest survival was seen in patients r and omised to R6C ( median 20.3 months , 41 % surviving at 2 years ) but there were no statistically significant differences between treatment arms or treatment factors ( carboplatin versus no carboplatin , accelerated versus conventional radiotherapy ) . Haematological toxicity was significantly greater in patients treated with carboplatin and oesophageal toxicity was significantly greater and more protracted in patients treated with accelerated radiotherapy . CONCLUSIONS This study failed to show a significant survival advantage for any of the treatment arms or factors . Halving overall treatment time result ed in significantly greater oesophageal toxicity with no suggestion of a survival advantage PURPOSE This r and omized phase II trial was conducted to compare the overall response rate ( ORR ) of gemcitabine plus cisplatin combination followed by sequential radiotherapy ( RT ) ( arm A ) versus RT alone ( arm B ) in chemonaive patients with stage IIIA or IIIB non-small cell lung cancer ( NSCLC ) . Secondary objectives were to evaluate time to progressive disease ( TTPD ) , overall survival , and treatment tolerability in both arms . PATIENTS AND METHODS Eligible patients were required to have stage IIIA or stage IIIB NSCLC , no previous chemotherapy , ECOG performance status of 0 - 2 , bidimensionally measurable disease , and age 18 to 75 years . Patients r and omized in arm A were given 3 cycles of induction chemotherapy with gemcitabine 1250 mg/m(2 ) on days 1 and 8 , plus cisplatin 80 mg/m(2 ) on day 1 , every 21 days , followed by RT . In both arms , total dosage of RT was 63 Gy given in 34 fractions . Treatment continued until disease progression or unacceptable toxicity . RESULTS Enrolled patients in both arms ( 30 in each arm ) were well balanced for demographics and disease characteristics . The ORR , median TTPD and overall survival duration were 46.6/26.6 % , 9.9/7.1 months and 12.5/10.0 months for arm A and arm B , respectively . The chemoradiation arm ( arm A ) was associated with significantly higher hematologic toxicities ( anemia , neutropenia and thrombocytopenia ) and nonhematologic toxicities ( nausea , vomiting , paresthesias and alopecia ) . CONCLUSION Sequential chemoradiation seems to be more effective than radiation alone , with acceptable toxicity profile . Confirmation phase III studies are warranted BACKGROUND AND METHODS Cisplatin ( cis-diamminedichloroplatinum ) has been reported to enhance the cell-killing effect of radiation , an effect whose intensity varies with the schedule of administration . We r and omly assigned 331 patients with nonmetastatic inoperable non-small-cell lung cancer to one of three treatments : radiotherapy for two weeks ( 3 Gy given 10 times , in five fractions a week ) , followed by a three-week rest period and then radiotherapy for two more weeks ( 2.5 Gy given 10 times , five fractions a week ) ; radiotherapy on the same schedule , combined with 30 mg of cisplatin per square meter of body-surface area , given on the first day of each treatment week ; or radiotherapy on the same schedule , combined with 6 mg of cisplatin per square meter , given daily before radiotherapy . RESULTS Survival was significantly improved in the radiotherapy-daily-cisplatin group as compared with the radiotherapy group ( P = 0.009 ) : survival in the radiotherapy-daily-cisplatin group was 54 percent at one year , 26 percent at two years , and 16 percent at three years , as compared with 46 percent , 13 percent , and 2 percent , respectively , in the radiotherapy group . Survival in the radiotherapy-weekly-cisplatin group was intermediate ( 44 percent , 19 percent , and 13 percent ) and not significantly different from survival in either of the other two groups . The survival benefit of daily combined treatment was due to improved control of local disease ( P = 0.003 ) . Survival without local recurrence was 59 percent at one year and 31 percent at two years in the radiotherapy-daily-cisplatin group ; 42 percent and 30 percent , respectively , in the radiotherapy-weekly-cisplatin group ; and 41 percent and 19 percent , respectively , in the radiotherapy group . Cisplatin induced nausea and vomiting in 86 percent of the patients given it weekly and in 78 percent of those given it daily ; these effects were severe in 26 percent and 28 percent , respectively . CONCLUSIONS Cisplatin , given daily in combination with the radiotherapy described here to patients with nonmetastatic but inoperable non-small-cell lung cancer , improved rates of survival and control of local disease at the price of substantial side effects BACKGROUND The treatment results of radiotherapy in stage III non-small-cell lung cancer are very poor . Several phase II studies showed that neoadjuvant chemotherapy followed by radiotherapy was feasible in this patient group and suggested that treatment outcome might improve . A r and omized phase II study was performed addressing the response rate and morbidity of high-dose split course radiotherapy ( RT ) versus the same radiotherapy preceded by high-dose chemotherapy ( CT ) in patients with stage III non-small-cell lung cancer . PATIENTS AND METHODS Seventy eligible patients were r and omized in this study .  CT consisted of cisplatin 100 mg/m2 days 1 and 22 , and vindesine 3 mg/m2 on days 1 , 8 , 22 and 29 . Radiotherapy started on day 43 in the combined arm and immediately in the RT-only arm . The primary tumour and the regional nodes were treated by 30 Gy/10 fractions/2 weeks and after the split by a second course of 25 Gy/10 fractions/2 weeks . In the combined arm a third CT cycle was planned during the split between RT courses . RESULTS In the CT + RT arm 34 patients were evaluable for response and toxicity and 30 patients in the RT only arm . After completion of treatment 7 patients had a complete response ( 2 in the CT plus RT arm , 5 in the RT alone arm ) and 26 patients a partial response ( 13 in the CT plus RT arm , 13 in the RT alone arm ) for an overall response rate of 52 % ( 95 % CI 39%-65 % ) . Acute toxicity was worse in the combined treatment arm with grade 4 leucocytopenia in 8 patients and thrombocytopenia grade 4 in one patient . Three patients had reversible renal toxicity grade 2 . There was one toxic death in the RT plus CT arm . There was no enhancement of acute or late radiation pulmonary or oesophageal toxicity . Time to progressive disease ( median 30 vs. 35 weeks ) and overall survival time ( median 12 months ) were equal in both treatment arms . CONCLUSION High-dose radiotherapy preceded by high-dose chemotherapy was more toxic than radiotherapy alone and did not result in this study in any benefit in terms of response rate , time to progressive disease and overall survival The purpose of this study was to determine the feasibility of additional chemotherapy beyond 5 weeks of vinblastine-cisplatin followed by radiation therapy for patients with stage III non-small cell lung cancer . In this r and omized phase II trial , the goal was to determine , in a similar population of patients , the toxicity of either of two additional chemotherapy programs . Ninety-one patients with stage III non-small cell lung cancer received the same induction regime of vinblastine/cisplatin/radiotherapy . In patients r and omized to regime 1 , an additional four cycles of vinblastine/cisplatin were given after the radiotherapy . In regimen 2 , six weekly doses of carboplatin were given concurrent with the radiotherapy . The additional four cycles of vinblastine and cisplatin were completed by 34 % of patients ; the concurrent carboplatin program was completed by 70 % of patients . Grade 3 or 4 granulocytopenia occurred in 53 % of patients on regime 1 versus 17 % on regime 2 ( p < 0.003 ) ; grade 3 or 4 nausea/vomiting occurred in 20 % of those on regime 1 versus 7 % on regimen 2 ( p = 0.175 ) . Response rates and survival were similar for the two regimens , with approximately 30 % of patients surviving at 2 years . Given the reduced toxicity and the improved capacity to complete the planned therapy with the concurrent carboplatin treatment , this regimen will be further examined in a phase III trial PURPOSE A phase III study was performed to determine whether concurrent or sequential treatment with radiotherapy ( RT ) and chemotherapy ( CT ) improves survival in unresectable stage III non-small-cell lung cancer ( NSCLC ) . PATIENTS AND METHODS Patients were assigned to the two treatment arms . In the concurrent arm , chemotherapy consisted of cisplatin ( 80 mg/m(2 ) on days 1 and 29 ) , vindesine ( 3 mg/m(2 ) on days 1 , 8 , 29 , and 36 ) , and mitomycin ( 8 mg/m(2 ) on days 1 and 29 ) . RT began on day 2 at a dose of 28 Gy ( 2 Gy per fraction and 5 fractions per week for a total of 14 fractions ) followed by a rest period of 10 days , and then repeated . In the sequential arm , the same CT was given , but RT was initiated after completing CT and consisted of 56 Gy ( 2 Gy per fraction and 5 fractions per week for a total of 28 fractions ) . RESULTS Three hundred twenty patients were entered onto the study . Pretreatment characteristics were well balanced between the treatment arms . The response rate for the concurrent arm was significantly higher ( 84 . 0 % ) than that of the sequential arm ( 66 % ) ( P = .0002 ) . The median survival duration was significantly superior in patients receiving concurrent therapy ( 16.5 months ) , as compared with those receiving sequential therapy ( 13.3 months ) ( P = .03998 ) . Two- , 3- , 4- , and 5-year survival rates in the concurrent group ( 34.6 % , 22.3 % , 16.9 % , and 15.8 % , respectively ) were better than those in the sequential group ( 27.4 % , 14.7 % , 10.1 % , and 8.9 % , respectively ) . Myelosuppression was significantly greater among patients on the concurrent arm than on the sequential arm ( P = .0001 ) . CONCLUSION In selected patients with unresectable stage III NSCLC , the concurrent approach yields a significantly increased response rate and enhanced median survival duration when compared with the sequential approach 7005 Background : St and ard therapy for unresectable stage III NSCLC includes concomitant chemoradiotherapy . In CALGB 39801 , we evaluated whether the addition of induction chemotherapy prior to CT/XRT would result in improved survival . METHODS Between 10/1998 and 5/2002 , 366 stage III patients ( pts ) were r and omized to either immediate CT/XRT [ carboplatin AUC of 2 and paclitaxel 50 mg/m2 each given weekly during 66 Gy chest XRT to ; arm 1 ( 182 pts ) ] or two  cycles  of carboplatin AUC 6 and paclitaxel 200 mg/m2 given q 21 days x 2 cycles followed by identical CT/XRT ;  arm 2 ( 184 pts ) . The accrual goal was 360 patients . 290 deaths were required to have 80 % power to detect a 40 % increase in median survival assuming a one-tailed log-rank test conducted at the 0.025 level of significance . RESULTS 34 % of pts were female , 66 % male and 63 % were age 60 or older . Grade 3 or 4 toxicities during induction chemotherapy consisted mainly of neutropenia ( 17%/21 % ) . During CT/XRT , grade 3/4 neutropenia was noted in 11%/4 % ( arm 1 ) versus 21%/6 % ( arm 2 ) , grade 3 anemia was 5 % vs 11 % , grade 3/4 fatigue 16%/1 % vs 16%/4 % , esophagitis 30%/1 % vs 28%/7 % , and dyspnea 9%/3 % vs 15%/4 % . Overall , 4 toxicities were experienced by 24 % of patients on arm 1 versus 41 % on arm 2 ( p=0.001 ) . With 254 of 290 targeted deaths , median survival on arm 1 is 11.4 months versus 14 months on arm 2 ( p=0.154 ) . One year survival estimates are 48 % ( 41%-57 % ) and 54 % ( 47%-62 % ) respectively . CONCLUSION The median survival achieved in each of the treatment groups is low compared to other recent experiences in the literature . The reason(s ) for this are uncertain . The addition of induction chemotherapy to immediate concurrent CT/XRT is associated with a 2.6 month increase in median survival . However these findings are not sufficient to reject the null hypothesis of no treatment difference between the two study arms . Further follow up of this data set is required . Our results do not support the use of induction chemotherapy followed by CT/XRT as evidence based st and ard of care for patients with unresectable stage III NSCLC . [ Table : see text ] BACKGROUND For many years , high dose radiation therapy was the st and ard treatment for patients with locally or regionally advanced non-small-cell lung cancer ( NSCLC ) , despite a 5-year survival rate of only 3%-10 % following such therapy . From May 1984 through May 1987 , the Cancer and Leukemia Group B ( CALGB ) conducted a r and omized trial that showed that induction chemotherapy before radiation therapy improved survival during the first 3 years of follow-up . PURPOSE This report provides data for 7 years of follow-up of patients enrolled in the CALGB trial . METHODS The patient population consisted of individuals who had clinical or surgical stage III , histologically documented NSCLC ; a CALGB performance status of 0 - 1 ; less than 5 % loss of body weight in the 3 months preceding diagnosis ; and radiographically visible disease . Patients were r and omly assigned to receive either 1 ) cisplatin ( 100 mg/m2 body surface area intravenously on days 1 and 29 ) and vinblastine ( 5 mg/m2 body surface area intravenously weekly on days 1 , 8 , 15 , 22 , and 29 ) followed by radiation therapy with 6000 cGy given in 30 fractions beginning on day 50 ( CT-RT group ) or 2 ) radiation therapy with 6000 cGy alone beginning on day 1 ( RT group ) for a maximum duration of 6 - 7 weeks . Patients were evaluated for tumor regression if they had measurable or evaluable disease and were monitored for toxic effects , disease progression , and date of death . RESULTS There were 78 eligible patients r and omly assigned to the CT-RT group and 77 r and omly assigned to the RT group . Both groups were similar in terms of sex , age , histologic cell type , performance status , substage of disease , and whether staging had been clinical or surgical . All patients had measurable or evaluable disease at the time of r and om assignment to treatment groups . Both groups received a similar quantity and quality of radiation therapy . As previously reported , the rate of tumor response , as determined radiographically , was 56 % for the CT-RT group and 43 % for the RT group ( P = .092 ) . After more than 7 years of follow-up , the median survival remains greater for the CT-RT group ( 13.7 months ) than for the RT group ( 9.6 months ) ( P = .012 ) as ascertained by the logrank test ( two-sided ) . The percentages of patients surviving after years 1 through 7 were 54 , 26 , 24 , 19 , 17 , 13 , and 13 for the CT-RT group and 40 , 13 , 10 , 7 , 6 , 6 , and 6 for the RT group . CONCLUSIONS Long-term follow-up confirms that patients with stage III NSCLC who receive 5 weeks of chemotherapy with cisplatin and vinblastine before radiation therapy have a 4.1-month increase in median survival . The use of sequential chemotherapy-radiotherapy increases the projected proportion of 5-year survivors by a factor of 2.8 compared with that of radiotherapy alone . However , inasmuch as 80%-85 % of such patients still die within 5 years and because treatment failure occurs both in the irradiated field and at distant sites in patients receiving either sequential chemotherapy-radiotherapy or radiotherapy alone , the need for further improvements in both the local and systemic treatment of this disease persists This prospect i ve r and omized trial compared neoadjuvant chemotherapy followed by local-regional radiotherapy ( study group ) with radiotherapy alone ( control group ) in 506 patients with locally advanced non-small-cell lung cancer . The study group received three cycles of cisplatin , ifosfamide with Mesna , and mitomycin C at 21-day intervals . Radiotherapy was delivered up to a dose of 60 Gy . Evaluable patients numbered 460 . In the study group , 228 patients were assessed for tumor response after chemotherapy : 13 ( 5.7 % ) had a complete response ; 103 ( 43.2 % ) , a partial response ; 48 ( 21 % ) showed no change ; and 74 patients ( 31.1 % ) had progressive disease . These patients then received chest irradiation , which was well tolerated . On completion of radiotherapy , 16.2 % of the study group and 6 % of the control group had a complete response . No change was seen in 10.1 % of study patients and 15.5 % of control patients . Respective rates for disease progression were 27.6 % and 42.3 % . Actuarial 2-year survival was 20 % in the study group and 7.4 % in the control group PURPOSE To test the concept of taxane sequencing in combined-modality therapy , this phase II trial ( S9504 ) evaluated consolidation docetaxel after concurrent chemoradiotherapy in patients with pathologically documented stage IIIB non-small-cell lung cancer ( NSCLC ) . Results were compared with those of the predecessor study ( S9019 ) with identical eligibility , staging criteria , and treatment , excepting docetaxel consolidation . PATIENTS AND METHODS Treatment consisted of cisplatin 50 mg/m2 on days 1 , 8 , 29 , and 36 , etoposide 50 mg/m2 on days 1 through 5 and 29 through 33 , and concurrent thoracic radiotherapy ( total dose of 61 Gy ) . Consolidation docetaxel started 4 to 6 weeks after chemoradiotherapy at an initial dose of 75 mg/m2 . RESULTS Stage subsets ( tumor-node-metastasis system ) in 83 eligible patients were as follows : T4N0/1 , 31 patients ( 37 % ) ; T4N2 , 22 patients ( 27 % ) , and T1 - 3N3 , 30 patients ( 36 % ) . Concurrent chemoradiotherapy was generally well tolerated , but two patients died from probable radiation-associated pneumonitis . Neutropenia during consolidation docetaxel was common ( 57 % with grade 4 ) and most frequent during escalation to 100 mg/m2 . Median progression-free survival was 16 months , median survival was 26 months , and 1- , 2- , and 3-year survival rates were 76 % , 54 % , and 37 % , respectively . Brain metastasis was the most common site of failure . In S9019 , median survival was 15 months and 1- , 2- , and 3-year survival rates were 58 % , 34 % , and 17 % , respectively . CONCLUSION Consolidation docetaxel after concurrent chemoradiotherapy in stage IIIB NSCLC is feasible and generally tolerable , and results compare favorably with the predecessor trial S9019 . Nevertheless , this study remains hypothesis-generating and does not provide definitive evidence of the benefit of this approach . Phase III trials evaluating the S9504 regimen have been initiated to vali date these results OBJECTIVE The rate of complete resection ( 50 % ) and the 5-year survival ( 30 % ) for non-small cell lung carcinomas of the superior sulcus have not changed for 40 years . Recently , combined modality therapy has improved outcome in other subsets of locally advanced non-small cell lung carcinoma . This trial tested the feasibility of induction chemoradiation and surgical resection in non-small cell lung carcinoma of the superior sulcus with the ultimate aim of improving resectability and survival . METHODS Patients with mediastinoscopy-negative T3 - 4 N0 - 1 superior sulcus non-small cell lung carcinoma received 2 cycles of cisplatin and etoposide chemotherapy concurrent with 45 Gy of radiation .  Patients with stable or responding disease underwent thoracotomy 3 to 5 weeks later . All patients received 2 more cycles of chemotherapy and were followed up by serial radiographs and scans . Survival was calculated by the Kaplan-Meier method and prognostic factors were assessed for significance by Cox regression analysis . RESULTS From April 1995 to September 1999 , 111 eligible patients ( 77 men , 34 women ) were entered in the study , including 80 ( 72.1 % ) with T3 and 31 with T4 tumors . Induction therapy was completed as planned in 102 ( 92 % ) patients . There were 3 treatment-related deaths ( 2.7 % ) . Cytopenia was the main grade 3 to 4 toxicity . Of 95 patients eligible for surgery , 83 underwent thoracotomy , 2 ( 2.4 % ) died postoperatively , and 76 ( 92 % ) had a complete resection . Fifty-four ( 65 % ) thoracotomy specimens showed either a pathologic complete response or minimal microscopic disease . The 2-year survival was 55 % for all eligible patients and 70 % for patients who had a complete resection . To date , survival is not significantly influenced by patient sex , T status , or pathologic response . CONCLUSIONS ( 1 ) This combined modality treatment is feasible in a multi-institutional setting ; ( 2 ) the pathologic complete response rates were high ; and ( 3 ) resectability and overall survival were improved compared with historical experience , especially for T4 tumors , which usually have a grim prognosis The aim of this r and omised trial was to investigate the effect of induction chemotherapy before radiotherapy on survival in 302 patients with non-resectable squamous cell carcinoma of the lung .  Radiotherapy , 56 Gy to the chest , was given to 154 patients and combined treatment , with chemotherapy preceding the radiotherapy , to 148 patients .  Chemotherapy consisted of three courses of cisplatin ( 120 mg/m2 ) and etoposide ( 100 mg/m2 i.v . for 3 days ) administered every fourth week . Median survival was 10.5 months in the radiotherapy arm and 11 months in the combined treatment arm . The 2-year survival rate was 17 % in the radiotherapy arm and 21 % in the combined treatment arm . Addition of chemotherapy seemed to significantly improve survival , according to the Cox multivariate analysis ( P = 0.04 ) , but as only a trend according to life-table analysis ( P = 0.11 ) . Chemotherapy also accomplished a trend towards improved local control ( P = 0.08 ) and towards decreased metastatic disease ( P = 0.10 ) . 2 patients in the combined treatment arm , but none in the radiotherapy arm , died from toxicity . The conclusion was that the value of the chemotherapy used in this study was very modest , but the results strongly support further research for more efficient drugs and combinations Assessment of health related quality of life has become an important endpoint in many cancer clinical trials . Because the participants of these trials often experience disease and treatment related morbidity and mortality , non-r and om missing assessment s are inevitable . Examples are presented from several such trials that illustrate the impact of missing data on the analysis of QOL in these trials . The sensitivity of different analyses depends on the proportion of assessment s that are missing and the strength of the association of the underlying reasons for missing data with disease and treatment related morbidity and mortality . In the setting of clinical trials of cancer therapy , the assumption that the data are missing completely at r and om ( MCAR ) and analyses of complete cases is usually unjustified . Further , the assumption of missing at r and om ( MAR ) may also be violated in many trials and models appropriate for non-ignorable missing data should be explored . Recommendations are presented to minimize missing data , to obtain useful documentation concerning the reasons for missing data and to perform sensitivity analyses In patients with non-metastatic but inoperable non-small cell lung cancer that is locally too extensive for radical radiotherapy ( RT )  , but who have good performance status , it is important to determine whether thoracic RT should be the minimum that is required to palliate thoracic symptoms or whether treatment should be more intensive , with the aim of prolonging survival . A total of 509 such patients from 11 centres in the UK between November 1989 and October 1992 were admitted to a trial comparing palliative versus more intensive RT with respect to survival and quality of life . They were allocated at r and om to receive thoracic RT with either 17 Gy in two fractions ( F2 ) 1 week apart ( 255 patients ) or 39 Gy in 13 fractions ( F13 ) 5 days per week ( 254 patients ) . Survival was better in the F13 group , the median survival periods being 7 months in the F2 group compared with 9 months in the F13 group , and the survival rates 31 % and 36 % at one year and 9 % and 12 % at 2 years , respectively ( hazard ratio = 0.82 ; 95 % CI0.69 - 0.99 ) . There was a suggestion of a trend towards greater benefit in fitter patients . Metastases appeared earlier in the F2 group . As recorded by patients using the Rotterdam Symptom Checklist , the commonest symptoms on admission were cough , shortness of breath , tiredness , lack of energy , worrying and chest pain . These were more rapidly palliated by the F2 regimen . Psychological distress was generally lower in the F13 group . Three patients ( two F13 , one F2 ) exhibited evidence of myelopathy . As recorded by patients using a diary card , 76 % of the F2 compared with 81 % of the F13 patients had dysphagia associated with their RT . This was transient , lasting for a median of 6.5 days in the F2 group compared with 14 days in the F13 group . In conclusion , the F2 regimen had a more rapid palliative effect . In the F13 group , although treatment-related dysphagia was worse , survival was longer
PURPOSE To conduct a systematic review to determine the most effective therapy for patients with unresected stage III non-small cell lung cancer .