Adjuvant chemotherapy following radical surgery for non-small-cell lung cancer: a randomized study on 70 patients. Adjuvant vinorelbine plus cisplatin versus observation in patients with completely resected stage IB-IIIA non-small-cell lung cancer (Adjuvant Navelbine International Trialist Association [ANITA]): a randomised controlled trial. Long-term follow-up of patients enrolled in a randomized trial comparing perioperative chemotherapy and surgery with surgery alone in resectable stage IIIA non-small-cell lung cancer. Postoperative adjuvant therapy for stage II non-small-cell lung cancer. Pre-operative chemotherapy in early stage resectable non-small-cell lung cancer: a randomized feasibility study justifying a multicentre phase III trial Randomized study of adjuvant chemotherapy for completely resected stage I, II, or IIIA non-small-cell Lung cancer. Vinorelbine plus cisplatin vs. observation in resected non-small-cell lung cancer. Randomised study of adjuvant chemotherapy for completely resected p-stage I–IIIA non-small cell lung cancer Cisplatin-based adjuvant chemotherapy in patients with completely resected non-small-cell lung cancer. The feasibility of creating a checklist for the assessment of the methodological quality both of randomised and non-randomised studies of health care interventions. A randomized phase III trial of adjuvant chemotherapy with UFT for completely resected pathological stage I non-small-cell lung cancer: the West Japan Study Group for Lung Cancer Surgery (WJSG)--the 4th study. Postoperative adjuvant chemotherapy with PVM (Cisplatin + Vindesine + Mitomycin C) and UFT (Uracil + Tegaful) in resected stage I-II NSCLC (non-small cell lung cancer): a randomized clinical trial. West Japan Study Group for lung cancer surgery (WJSG). A randomized trial of postoperative UFT therapy in p stage I, II non-small cell lung cancer: North-east Japan Study Group for Lung Cancer Surgery. Failure of the perioperative PCV neoadjuvant polychemotherapy in resectable bronchogenic non‐small cell carcinoma results from a randomized phase II trial A randomized trial comparing induction chemotherapy followed by surgery with surgery alone for patients with stage IIIA N2 non-small cell lung cancer (JCOG 9209). Chemotherapy for patients with non-small cell lung cancer: the surgical setting of the Big Lung Trial. Postsurgical chemotherapy in stage IB nonsmall cell lung cancer: Long-term survival in a randomized study. Preoperative chemotherapy followed by surgery compared with primary surgery in resectable stage I (except T1N0), II, and IIIa non-small-cell lung cancer. Adjuvant chemotherapy in stage IB non-small cell lung cancer (NSCLC): Update of Cancer and Leukemia Group B (CALGB) protocol 9633. Indirect comparisons of competing interventions. Adjuvant chemotherapy after complete resection in non-small-cell lung cancer. West Japan Study Group for Lung Cancer Surgery. A randomized trial of postoperative adjuvant chemotherapy in non-small cell lung cancer (the second cooperative study). The Study Group of Adjuvant Chemotherapy for Lung Cancer (Chubu, Japan). Indirect comparison in evaluating relative efficacy illustrated by antimicrobial prophylaxis in colorectal surgery. Adjuvant chemotherapy for completely resected stage III non-small-cell lung cancer. Results of a randomized prospective study. The Japan Clinical Oncology Group. Adjuvant chemotherapy with cyclophosphamide, doxorubicin, and cisplatin in patients with completely resected stage I non-small-cell lung cancer. The Lung Cancer Study Group. A randomized trial comparing adjuvant chemotherapy versus surgery alone for completely resected pN2 non-small cell lung cancer (JCOG9304). A small randomized phase III single-center trial on postoperative UFT administration in patients with completely resected non-small cell lung cancer A randomized trial of adjuvant chemotherapy with uracil-tegafur for adenocarcinoma of the lung. Postoperative adjuvant cisplatin, vindesine, plus uracil-tegafur chemotherapy increased survival of patients with completely resected p-stage I non-small cell lung cancer. Preresectional chemotherapy in stage IIIA non-small-cell lung cancer: a 7-year assessment of a randomized controlled trial. Randomized trial of neoadjuvant therapy for lung cancer: interim analysis. [A clinicopathologic study on neoadjuvant chemotherapy in the treatment of non-small-cell lung cancer]. Adjuvant chemotherapy after radical surgery for non-small-cell lung cancer: a randomized study. Preoperative chemotherapy increases cytokine production after lung cancer surgery.
OBJECTIVE To evaluate the efficacy of adjuvant chemotherapy after radical surgery for non-small-cell lung cancer ( NSCLC ) . METHODS Seventy patients with NSCLC ( stages I-III ) undergoing radical surgery were r and omized into two groups . Group 1 ( n = 35 ) : combination group , which received adjuvant chemotherapy with cyclophosphamide 300 mg/m2 , vincristine 1.4 mg/m2 , adriamycin 50 mg/m2 , and lomustine 50 mg/m2 on day 1 , and cisplatin 20 mg/m2 on days 1 - 5 . The treatment was repeated every 4 - 6 weeks for 4 cycles , followed by oral administration of ftorafur ( FT-207 ) 600 - 900 mg/d for 1 year . Group 2 ( n = 35 ) : surgery group , which received surgical treatment only . RESULTS The overall 5-year survival rate was 48.6 % in the combination group versus 31.4 % in the surgery group , and difference between the two groups was not statistically significant ( chi 2 = 3.09 , P > 0.05 ) . The 5-year survival rate for patients with stage III disease was 44 % and 20.8 % in the combination and surgery groups , respectively , showing a statistically significant difference ( chi 2 = 5.28 , P < 0.025 ) . The 5-year survival rates of patients in stages I-II in the two groups were 60.0 % and 54.5 % , respectively , and were not significantly different ( chi 2 = 0.03 , P > 0.75 ) . CONCLUSION Postoperative adjuvant chemotherapy provides statistically significant improvement in the 5-year survival rate only in patients with stage III NSCLC BACKGROUND Whether adjuvant chemotherapy improves survival of patients with non-small-cell lung cancer ( NSCLC ) is not known . We aim ed to compare the effect of adjuvant vinorelbine plus cisplatin versus observation on survival in patients with completely resected NSCLC . METHODS 840 patients with stage IB-IIIA NSCLC from 101 centres in 14 countries were r and omly assigned to observation ( n=433 ) or to 30 mg/m(2 ) vinorelbine plus 100 mg/m(2 ) cisplatin ( n=407 ) . Postoperative radiotherapy was not m and atory and was undertaken according to every centre 's policy . The primary endpoint was overall survival . Analysis was by intention to treat . This trial is registered as an International St and ard R and omised Controlled Trial , number IS RCT N95053737 . FINDINGS 367 patients in the chemotherapy group and 431 in the control group received their assigned treatment . 301 ( 36 % ) patients had stage IB disease , 203 ( 24 % ) had stage II disease , and 325 ( 39 % ) had stage IIIA disease . Tolerance to chemotherapy mainly included neutropenia in 335 ( 92 % ) patients and febrile neutropenia in 34 ( 9 % ) ; seven ( 2 % ) toxic deaths were also recorded . Compliance was greater with cisplatin than with vinorelbine ( median dose intensity 89 % [ range 17 - 108 ] vs 59 % [ 17 - 100 ] ) . After a median follow-up of 76 months ( range 43 - 116 ) , median survival was 65.7 months ( 95 % CI 47.9 - 88.5 ) in the chemotherapy group and 43.7 ( 35.7 - 52.3 ) months in the observation group . Adjusted risk for death was significantly reduced in patients assigned chemotherapy compared with controls ( hazard ratio 0.80 [ 95 % CI 0.66 - 0.96 ] ; p=0.017 ) . Overall survival at 5 years with chemotherapy improved by 8.6 % , which was maintained at 7 years ( 8.4 % ) . INTERPRETATION Adjuvant vinorelbine plus cisplatin extends survival in patients with completely resected NSCLC , better defining indication of adjuvant chemotherapy Our previously reported r and omized study of patients with untreated , potentially resectable clinical stage IIIA non-small-cell lung cancer found that patients treated with perioperative chemotherapy and surgery had a significant increase in median survival compared to patients treated with surgery alone . We have now re-analyzed the results of the study with a median time from r and om allocation to analysis for all patients of 82 months . The increase in survival conferred by perioperative chemotherapy was maintained during the period of extended observation BACKGROUND Stage II non-small-cell lung cancer is regarded as one of the early lung cancers . Although resection , including the mediastinal lymph nodes , is currently regarded as the st and ard treatment , the survival rate of this disease is not encouraging . It is well known that the most common causes of death are locoregional recurrences or distant metastases , or both . However , the best adjuvant treatment to improve survival is as controversial an issue as ever . METHODS This study was design ed as a r and omized , blinded , two-armed study with operation and adjuvant radiotherapy in one arm , versus operation and adjuvant mitomycin C ( 10 mg/m2 ) , vinblastine ( 6 mg/m2 ) , and cisplatin ( 100 mg/m2 ) ( MVP ) chemotherapy in the other arm . We assigned 57 resected patients with pathologic proven stage II non-small cell lung cancer to the groups according to our eligibility criteria . RESULTS The most common pattern of recurrence was distant metastases , and nearly all the recurrences ( 17 of 18 patients ) in both groups were found within 2 years after operation . The rates of the locoregional and distant metastases were 3.6 % and 46.4 % in the adjuvant radiotherapy group and 6.9 % and 10.3 % in the adjuvant chemotherapy group ( p = 0.018 ) . The 5-year disease-free survival rates were 52.0 % in the adjuvant radiotherapy group and 74.0 % in the adjuvant chemotherapy group ( p = 0.16 , log-rank test ) . The 2-year , 5-year , and 6-year survival portions were 60.3 % , 56.5 % , and 28.3 % in the adjuvant radiotherapy group , and 82.8 % , 70.1 % , and 60.1 % in the adjuvant chemotherapy group ( p = 0.01 , p = 0.17 , and p = 0.03 , Z-test ) . The difference of the actuarial survival between these two groups was somewhat significant ( p = 0.09 , log-rank test ) . CONCLUSIONS Our results suggest that the addition of adjuvant MVP chemotherapy may reduce the distant metastasis rates and prolong the survival of the surgically resected stage II non-small-cell lung cancer patients Summary Surgical resection offers the best chance for cure for early stage non-small-cell lung cancer ( NSCLC , stage I , II , IIIA ) , but the 5-year survival rates are only moderate , with systemic relapse being the major cause of death . Pre-operative ( neo-adjuvant ) chemotherapy has shown promise in small trials restricted to stage IIIA patients . We believe similar trials are now appropriate in all stages of operable lung cancer . A feasibility study was performed in 22 patients with early stage ( IB , II , IIIA ) resectable NSCLC ; r and omized to either three cycles of chemotherapy [ mitomycin-C 8 mg m–2 , vinblastine 6 mg m–2 and cisplatin 50 mg m–2 ( MVP ) ] followed by surgery ( n = 11 ) , or to surgery alone .  Of 40 eligible patients , 22 agreed to participate ( feasibility 55 % ) and all complied with the full treatment schedule . All symptomatic patients achieved either complete ( 50 % ) or partial ( 50 % ) relief of tumour-related symptoms with pre-operative chemotherapy . Fifty-five per cent achieved objective tumour response , and a further 27 % minor tumour shrinkage ; none had progressive disease . Partial pathological response was seen in 50 % . No severe ( WHO grade III – IV ) toxicities occurred . No significant deterioration in quality of life was detected during chemotherapy . Pre-operative MVP chemotherapy is feasible in early stage NSCLC , and this study has now been initiated as a UK-wide Medical Research Council phase III trial BACKGROUND Surgery is the primary treatment for patients with stage I , II , or IIIA non-small-cell lung cancer ( NSCLC ) . However , long-term survival of NSCLC patients after surgery alone is largely unsatisfactory , and the role of adjuvant chemotherapy in patient survival has not yet been established . METHODS Between January 1994 and January 1999 , 1209 patients with stage I , II , or IIIA NSCLC were r and omly assigned to receive mitomycin C ( 8 mg/m2 on day 1 ) , vindesine ( 3 mg/m2 on days 1 and 8) , and cisplatin ( 100 mg/m2 on day 1 ) every 3 weeks for three cycles ( MVP group ; n = 606 ) or no treatment ( control group ; n = 603 ) after complete resection . R and omization was stratified by investigational center , tumor size , lymph-node involvement , and the intention to perform radiotherapy . The primary endpoint was overall survival and secondary endpoints were progression-free survival and toxicity associated with adjuvant treatment . Survival curves were analyzed using the log-rank test . All statistical tests were two-sided . RESULTS After a median follow-up time of 64.5 months , there was no statistically significant difference between the two patient groups in overall survival ( hazard ratio = 0.96 , 95 % confidence interval = 0.81 to 1.13 ; P = .589 ) or progression-free survival ( hazard ratio = 0.89 , 95 % confidence interval = 0.76 to 1.03 ; P = .128 ) . Only 69 % of patients received the three planned cycles of MVP . Grade s 3 and 4 neutropenia occurred in 16 % and 12 % , respectively , of patients in the MVP arm . Radiotherapy was completed by 65 % of patients in the MVP arm and by 82 % of patients in the control group . In the multivariable analysis , only disease stage and sex were associated with survival . CONCLUSION This r and omized trial failed to prospect ively confirm a statistically significant role for adjuvant chemotherapy in completely resected NSCLC . Given the poor compliance with the MVP regimen used in this study , future studies should explore more effective treatments BACKGROUND We undertook to determine whether adjuvant vinorelbine plus cisplatin prolongs overall survival among patients with completely resected early-stage non-small-cell lung cancer . METHODS We r and omly assigned patients with completely resected stage IB or stage II non-small-cell lung cancer to vinorelbine plus cisplatin or to observation . The primary end point was overall survival ; principal secondary end points were recurrence-free survival and the toxicity and safety of the regimen . RESULTS A total of 482 patients underwent r and omization to vinorelbine plus cisplatin ( 242 patients ) or observation ( 240 ) ; 45 percent of the patients had pathological stage IB disease and 55 percent had stage II , and all had an Eastern Cooperative Oncology Group performance status score of 0 or 1 . In both groups , the median age was 61 years , 65 percent were men , and 53 percent had adenocarcinomas . Chemotherapy caused neutropenia in 88 percent of patients ( including grade 3 febrile neutropenia in 7 percent ) and death from toxic effects in two patients ( 0.8 percent ) . Nonhematologic toxic effects of chemotherapy were fatigue ( 81 percent of patients ) , nausea ( 80 percent ) , anorexia ( 55 percent ) , vomiting ( 48 percent ) , neuropathy ( 48 percent ) , and constipation ( 47 percent ) , but severe ( grade 3 or greater ) toxic effects were uncommon ( < 10 percent ) . Overall survival was significantly prolonged in the chemotherapy group as compared with the observation group ( 94 vs. 73 months ; hazard ratio for death , 0.69 ; P=0.04 ) , as was relapse-free survival ( not reached vs. 46.7 months ; hazard ratio for recurrence , 0.60 ; P<0.001 ) . Five-year survival rates were 69 percent and 54 percent , respectively ( P=0.03 ) . CONCLUSIONS Adjuvant vinorelbine plus cisplatin has an acceptable level of toxicity and prolongs disease-free and overall survival among patients with completely resected early-stage non-small-cell lung cancer We evaluated the therapeutic usefulness of adjuvant chemotherapy in patients with completely resected non-small cell lung cancer ( NSCLC ) . We also examined the relation between DNA ploidy pattern and the response to chemotherapy .  A total of 267 patients with NSCLC ( pathologically documented stage I , II , or IIIA ) underwent complete resection , and DNA ploidy pattern was analysed . Patients with stage I disease ( n=172 ) were r and omly assigned to receive surgery alone ( group A ) or surgery followed by adjuvant chemotherapy ( UFT ( oral anti-cancer drug , a combination of Uracil and Tegaful ) 400 mg day−1 for 1 year after surgery ; group B ) . Stage II or IIIA disease patients ( n=95 ) were r and omly assigned to surgery alone ( group C ) or surgery followed by chemotherapy ( two 28-day courses of cisplatin 80 mg m−2 on day 1 plus vindesine 3 mg m−2 on days 1 and 8 , followed by UFT 400 mg day−1 for at least 1 year ; group D ) . Eight-year overall survival rate in patients with stage I disease was 74.2 % ( 95 % confidence interval ( CI ) : 64.4–84.0 % ) in group B and 57.6 % ( 95 % CI : 46.4–68.8 % ) in group A ( P=0.045 by log-rank test ) . In patients with stage II and IIIA disease , no difference was found between groups C and D. Analysis according to DNA ploidy pattern revealed no difference between the groups . Postoperative chemotherapy with UFT was suggested to be useful in patients with completely resected stage I NSCLC . No difference was seen in relation to DNA pattern in any treatment group BACKGROUND On the basis of a previous meta- analysis , the International Adjuvant Lung Cancer Trial was design ed to evaluate the effect of cisplatin-based adjuvant chemotherapy on survival after complete resection of non-small-cell lung cancer . METHODS We r and omly assigned patients either to three or four cycles of cisplatin-based chemotherapy or to observation . Before r and omization , each center determined the pathological stages to include , its policy for chemotherapy ( the dose of cisplatin and the drug to be combined with cisplatin ) , and its postoperative radiotherapy policy . The main end point was overall survival . RESULTS A total of 1867 patients underwent r and omization ; 36.5 percent had pathological stage I disease , 24.2 percent stage II , and 39.3 percent stage III . The drug allocated with cisplatin was etoposide in 56.5 percent of patients , vinorelbine in 26.8 percent , vinblastine in 11.0 percent , and vindesine in 5.8 percent . Of the 932 patients assigned to chemotherapy , 73.8 percent received at least 240 mg of cisplatin per square meter of body-surface area . The median duration of follow-up was 56 months . Patients assigned to chemotherapy had a significantly higher survival rate than those assigned to observation ( 44.5 percent vs. 40.4 percent at five years [ 469 deaths vs. 504 ] ; hazard ratio for death , 0.86 ; 95 percent confidence interval , 0.76 to 0.98 ; P<0.03 ) . Patients assigned to chemotherapy also had a significantly higher disease-free survival rate than those assigned to observation ( 39.4 percent vs. 34.3 percent at five years [ 518 events vs. 577 ] ; hazard ratio , 0.83 ; 95 percent confidence interval , 0.74 to 0.94 ; P<0.003 ) . There were no significant interactions with prespecified factors . Seven patients ( 0.8 percent ) died of chemotherapy-induced toxic effects . CONCLUSIONS Cisplatin-based adjuvant chemotherapy improves survival among patients with completely resected non-small-cell lung cancer OBJECTIVE : To test the feasibility of creating a valid and reliable checklist with the following features : appropriate for assessing both r and omised and non-r and omised studies ; provision of both an overall score for study quality and a profile of scores not only for the quality of reporting , internal validity ( bias and confounding ) and power , but also for external validity . DESIGN : A pilot version was first developed , based on epidemiological principles , review s , and existing checklists for r and omised studies . Face and content validity were assessed by three experienced review ers and reliability was determined using two raters assessing 10 r and omised and 10 non-r and omised studies . Using different raters , the checklist was revised and tested for internal consistency ( Kuder-Richardson 20 ) , test-retest and inter-rater reliability ( Spearman correlation coefficient and sign rank test ; kappa statistics ) , criterion validity , and respondent burden . MAIN RESULTS : The performance of the checklist improved considerably after revision of a pilot version . The Quality Index had high internal consistency ( KR-20 : 0.89 ) as did the subscales apart from external validity ( KR-20 : 0.54 ) . Test-retest ( r 0.88 ) and inter-rater ( r 0.75 ) reliability of the Quality Index were good . Reliability of the subscales varied from good ( bias ) to poor ( external validity ) . The Quality Index correlated highly with an existing , established instrument for assessing r and omised studies ( r 0.90 ) . There was little difference between its performance with non-r and omised and with r and omised studies . Raters took about 20 minutes to assess each paper ( range 10 to 45 minutes ) . CONCLUSIONS : This study has shown that it is feasible to develop a checklist that can be used to assess the method ological quality not only of r and omised controlled trials but also non-r and omised studies . It has also shown that it is possible to produce a checklist that provides a profile of the paper , alerting review ers to its particular method ological strengths and weaknesses . Further work is required to improve the checklist and the training of raters in the assessment of external validity PURPOSE To examine the efficacy of UFT , an oral 5-fluorouracil derivative agent , as post-operative adjuvant therapy for pathologic ( p- ) stage I non-small-cell lung cancer ( NSCLC ) , because a previous r and omized study had suggested it was efficacious for early-stage NSCLC patients . PATIENTS AND METHODS Patients with completely resected p-stage I , adenocarcinoma or squamous cell carcinoma were eligible . A total of 332 patients were r and omized to the  surgery-alone group ( control group ) and the treatment group ( UFT 400 mg/m(2 ) for 1 year after surgery , UFT group ) after stratification by the histologic types . RESULTS For all patients , the 5- and 8-year survival rates for the UFT group were 82.2 % and 73.0 % , and those for the control group were 75.9 % and 61.2 % , respectively ; no statistically significant improvement of survival was achieved by UFT administration ( P=0.105 ) . For Ad patients , the 5- and 8-year survival rates of the UFT group ( n=120 ) were 85.2 % and 79.5 % , respectively , which seemed better than those of the control group ( n=121 ) ( 79.2 % and 64.0 % , respectively ; P=0.081 ) . For squamous cell carcinoma patients , there was also no difference in survival between the control group ( n=48 ) and the UFT group ( n=43 ) ( P=0.762 ) . For all pT1 patients , the 5- and 8-year survival rates of the UFT group were 83.6 % and 82.1 % , respectively , significantly better than those of the control group ( 77.9 % and 57.6 % , respectively , P=0.036 ) ; UFT was not significantly effective for pT2 patients . For pT1 adenocarcinoma patients , UFT administration markedly improved the survival ( P=0.011 ) . CONCLUSION Post-operative UFT administration did not significantly improve post-operative survival of p-stage I NSCLC patients . Subset analyses suggested that UFT might be effective in pT1N0M0 adenocarcinoma patients OBJECTIVE The West Japan Study Group For Lung Cancer Surgery ( WJSG ) conducted a r and omized controlled trial in order to assess the usefulness of adjuvant chemotherapy for NSCLC . METHODS Patients with completely resected NSCLC ( stages I and II ) were enrolled in the trial . These patients were r and omized into two groups : a surgery alone group ; and a chemotherapy group which received intravenous administration of two courses of 4-week PVM chemotherapy ( 80 mg/m2 of Cisplatin on day 1 , 2 - 3 mg/m2 of Vindesine on day 1 and /or day 8 , and 8 mg/m2 of Mitomycin C on day 1 ) , after which they took 400 mg/day of UFT ( Uracil + Tegaful ) orally for 1 year . RESULTS Among 229 patients registered for the study from August 1988 to July 1990 , 225 were available cases ( 116 patients in the surgery alone group , and 109 patients in the chemotherapy group ) . No bias in prognostic factors could be found between the two groups . The 5-year survival rate was 71.1 % for the surgery-alone group and 76.8 % for the chemotherapy group with no significant difference observed . However , subset analysis demonstrated that PVM therapy improved the post operative survival of pT1N0 patients ( the 5-year survival rate : 75.3 % for the surgery alone group , and 90.7 % for the chemotherapy group P<0.05 ) . CONCLUSIONS It is interesting to find that among pT1N0 patients , who were not regarded as a target of chemotherapy , those receiving chemotherapy showed significantly better prognostic results . These findings suggest the necessity of further studies on the adjuvant chemotherapy , even in the early stages OBJECTIVE A prospect i ve r and omized trial was performed to investigate the prognostic advantage of postoperative adjuvant chemotherapy in patients with resected stage I-II non-small cell lung cancer ( NSCLC ) . PATIENTS AND METHODS From March 1992 to December 1994 , 221 patients with completely resected stage I-II primary NSCLC were enrolled and r and omly assigned to two groups , as follows : 2-year oral administration of Uracil plus Tegafur ( UFT ) ( adjuvant group , 109 patients ) , and surgical treatment alone ( control group , 110 patients ) . RESULTS The overall 5-year survival rates were 79 % for the adjuvant group and 75 % for the control group , and there was no statistical significance . The 5-year disease-free survival rates were 78 % for the adjuvant group and 71 % for the control group , and there was also no statistical significance . There have been seen no severe complications in the adjuvant group . The mean total dosages of UFT were about 75 % of maximum basic amount . CONCLUSIONS The UFT regimen was feasible . However , we have not observed any survival benefit in the adjuvant group . Larger trials are needed to confirm the effect of UFT to patients with resected NSCLC In 1985 , the authors began a phase II study to assess the PCV perioperative polychemotherapy ( cisplatin 100 mg/m2 , cyclophosphamide 600 mg/m2 , vindesine 3 mg/m2 ) in patients with resectable bronchogenic non‐small cell carcinoma . Patients were r and omized to receive either two preoperative courses of PCV chemotherapy , surgery , and two postoperative courses of PCV chemotherapy ( PCV group ) or immediate surgery ( surgery group ) . A staging procedure using the CT scan was performed before r and omization and , additionally , before surgery in the PCV group . There were 26 r and omized patients , 13 in each group . In the PCV group , 11 patients agreed to receive the two preoperative courses of chemotherapy .  A response was observed in five patients ( 45 % ) , and a progression was observed in four patients ( 36 % ) leading to a cancellation of surgery in two of them . Postoperative care was the same for each group . Although no death could be related to chemotherapy , it was decided to stop entering new patients into this trial because of the rate of preoperative progression in the PCV group OBJECTIVE We performed a prospect i ve r and omized trial in patients with potentially resectable stage IIIA N2 non-small cell lung cancer to confirm the efficacy of induction chemotherapy before surgical resection . METHODS Patients with stage IIIA N2 non-small cell lung cancer , all with histologically or cytologically confirmed metastases to the ipsilateral mediastinal lymph nodes , were r and omly assigned to receive either three cycles of induction chemotherapy ( cisplatin at 80 mg/m(2 ) on 1 day and vindesine at 3 mg/m(2 ) on 2 days ) followed by surgery or surgery alone . RESULTS This trial was prematurely terminated because the accrual rate was too slow , which lowered the study 's statistical power considerably . From June 1993 through April 1998 , a total of 62 patients were enrolled , and 31 patients were assigned to each treatment group . The objective clinical response rate of induction chemotherapy was 28 % . Complete resection was achieved in 20 patients in the induction chemotherapy group ( 65 % ) and 24 in the surgery alone group ( 77 % ) . Median follow-up was 6.2 years . Median overall survivals were 17 months for the induction group and 16 months for the surgery alone group . The estimated 1- , 3- , and 5-year survivals , respectively , were 68 % ( 95 % confidence interval 51%-85 % ) , 23 % ( 95 % confidence interval 8%-38 % ) , and 10 % ( 95 % confidence interval 0%-20 % ) for the induction chemotherapy group and 65 % ( 95 % confidence interval 48%-82 % ) , 26 % ( 95 % confidence interval 11%-41 % ) , and 22 % ( 95 % confidence interval 7%-37 % ) for the surgery alone group . There was no statistically significant difference in survival between the groups ( P = .5274 ) . Treatment-related death was not observed in either group . CONCLUSION This r and omized trial to compare induction chemotherapy ( cisplatin and vindesine ) followed by surgery with surgery alone for patients with stage IIIA N2 non-small cell lung cancer did not demonstrate a survival difference between the groups , although this may have been because the statistical power was limited OBJECTIVES The non-small cell lung cancer ( NSCLC ) meta- analysis suggested a survival benefit for cisplatin-based chemotherapy when given in addition to surgery , radical radiotherapy or ' best supportive care ' . However , it included many small trials and trials with differing eligibility criteria and chemotherapy regimens . The aim of the Big Lung Trial was therefore to run a large pragmatic trial to confirm the survival benefits seen in the meta- analysis . METHODS In the surgery setting , a total of 381 patients were r and omised to chemotherapy ( C , 192 patients ) or no chemotherapy ( NoC , 189 patients ) . C was three 3-weekly cycles of cisplatin/vindesine , mitomycin/ifosfamide/cisplatin , mitomycin/vinblastine/cisplatin or vinorelbine/cisplatin . RESULTS Chemotherapy was given before surgery in 3 % of patients whilst 97 % received adjuvant chemotherapy . Baseline characteristics were : median age 61 years , 69 % male , 48 % squamous cell , 93 % WHO PS 0 - 1 , 27 % stage I , 38 % stage II , and 34 % stage III . Complete resection was achieved in approximately 95 % of patients . In the C group , 13 % received no chemotherapy , 21 % one or two cycles , and 64 % all three cycles of their prescribed chemotherapy ( 60 % of the latter with no delays or modification ) . 30 % had grade 3/4 toxicity , mainly haematological , nausea/vomiting and neutropenic fever , and six patients were reported as having a treatment-related death . 198 ( 52 % ) of patients have died , but there is currently no evidence of a benefit in overall survival to the C group : HR 1.02 ( 95 % CI 0.77 - 1.35 ) , P = 0.90 ) . CONCLUSIONS This trial has failed to observe a survival benefit with adjuvant chemotherapy following complete resection of stage I-III NSCLC . However , the hazard ratio and 95 % confidence intervals are consistent with the previously reported meta- analysis and two large recently reported trials , which suggest a small survival benefit with cisplatin-based chemotherapy Although surgical resection is considered the adequate treatment in early stages of nonsmall cell lung cancer , long-term survival is not satisfactory and recurrence rate is high . We previously showed that postoperative chemotherapy at stage IB reduces recurrences and prolongs overall survival . We extended size and observation period of the study sample and performed a separate analysis for minimally resected patients . The trial was design ed as a r and omized , 2-armed study with postoperative adjuvant chemotherapy versus surgery alone as control group . All patients had stage IB disease ( pT2N0 ) assessed after a radical surgical procedure  ( defined as anatomical or minimal ) .  Chemotherapy consisted of cisplatin ( 100 mg/m2 day 1 ) and etoposide ( 120 mg/m2 days 1 - 3 ) for 6 cycles . The primary endpoint was overall survival ; secondary endpoint was disease-free survival ( DFS ) .  One hundred and forty patients entered the study : 70 were assigned to the adjuvant chemotherapy group and 70 to the control group .  Groups were homogeneous for conventional risk factors . There was no clinical ly significant morbidity associated to chemotherapy . Patients were followed for a mean period of 40.31 + /- 30.86 months . A significant difference in overall ( p = 0.02 ) and disease-free ( p = 0.0001 ) survival was observed between patients undergoing adjuvant chemotherapy vs. control group . Adjuvant chemotherapy significantly improved both overall ( p = 0.02 ) and DFS ( p = 0.003 ) of anatomically resected patients , but only the DFS ( p = 0.02 ) of minimally resected patients . Our results confirm that adjuvant chemotherapy may have a real impact on long-term survival in patients with stage IB nonsmall cell lung cancer being this effect especially evident for those anatomically resected PURPOSE To evaluate whether preoperative chemotherapy ( PCT ) could improve survival in resectable stage I ( except T1N0 ) , II , and IIIA non-small-cell lung cancer ( NSCLC ) . PATIENTS AND METHODS A r and omized trial compared PCT to primary surgery ( PRS ) . PCT consisted of two cycles of mitomycin ( 6 mg/m(2 ) , day 1 ) , ifosfamide ( 1.5 g/m(2 ) , days 1 to 3 ) and cisplatin ( 30 mg/m(2 ) , days 1 to 3 ) , and two additional postoperative cycles for responding patients . In both arms , patients with pT3 or pN2 disease received thoracic radiotherapy . RESULTS Three hundred fifty-five eligible patients were r and omized . Overall response to PCT was 64 % . There were two preoperative toxic deaths . Postoperative mortality was 6.7 % in the PCT arm and 4.5 % in the PRS arm ( P = .38 ) . Median survival was 37 months ( 95 % confidence interval [ CI ] , 26.7 to 48.3 ) for PCT and 26.0 months ( 95 % CI , 19.8 to 33.6 ) for PRS ( P = .15 ) . Survival differences between both arms increased from 3.8 % ( 95 % CI , 1.3 % to 25.1 % ) at 1 year to 8.6 % ( 95 % CI , 2.64 % to 24.4 % ) at 4 years . A quantitative interaction between N status and treatment was observed , with benefit confined to N0 to N1 disease ( relative risk [ RR ] , 0.68 ; 95 % CI , 0.49 to 0.96 ; P = .027 ) . After a nonsignificant excess of deaths during treatment , the effect of PCT was significantly favorable on survival ( RR , 0.74 ; 95 % CI , 0.56 to 0.99 ; P = .044 ) . Disease-free survival time was significantly longer in the PCT arm ( P = .033 ) . CONCLUSION Although impressive differences in median , 3-year , and 4-year survival were observed , they were not statistically significant , except for stage I and II disease 7007 Background : In 2004 , preliminary results of CALGB 9633 demonstrated statistically significant evidence that adjuvant chemotherapy with paclitaxel and carboplatin ( PC ) improved disease-free ( DFS ) and overall survival ( OS ) in resected stage IB NSCLC . Indeed , the study was closed early by the DSMB after a planned interim analysis demonstrated a p value for OS less than a prespecified stopping boundary . However , two larger trials , NCIC-JBR10 and ANITA , have shown significant OS advantages with adjuvant chemo , but failed to demonstrate improved survival in the stage IB subset . This report provides more mature data from CALGB 9633 . METHODS InCALGB 9633 , stage IB patients ( pts ) were r and omized following resection to paclitaxel 200 mg/m2 and carboplatin AUC 6 q3wks ×4 cycles or to observation . While initially planned to accrue 500 pts , the accrual rate was < 50 % of expected . Because slow accrual allowed longer observation times for each pt , the accrual target was reduced to 384 pts . OS is the primary endpoint . The re design ed study had 80 % power to detect a hazard ratio ( HR ) of 0.67 after 150 observed deaths using a 1-tailed logrank test conducted at the 0.05 level of significance . RESULTS Between 9/15/96 and 11/26/03 , 344 pts were r and omized . Median follow-up is 54 mo . Demographics and toxicity has been previously reported ( JCO Sup , 22:621a , 2004 ) . The current intent-to-treat analysis shows a significant improvement in DFS  favoring adjuvant chemo ( HR=0.74 ; 90 % 2-sided CI : 0.57 - 0.96 ; p=0.027 ) . There is a trend toward improvement in OS that is not significant ( HR=0.80 ; 90 % CI : 0.60 - 1.07 ; p=0.10 ) . There is , however , a significant advantage in 3-yr survival ( 79 % vs. 70 % ; p=0.045 ) . Five-yr survival is not different ( 60 % vs. 57 % ; p=0.32 ) , although median follow-up is < 5 yrs and CIs are wide . Continued follow-up is planned since only 131 of 150 deaths required for final analysis have been observed . CONCLUSIONS This up date d but " preliminary " analysis no longer shows a significant OS advantage  for adjuvant chemotherapy in stage IB NSCLC . However , the re- design ed study does not have adequate power to detect small differences in OS that may be clinical ly significant . Advantages in DFS and 3-yr survival support continued consideration of adjuvant PC in stage IB NSCLC . [ Table : see text ] OBJECTIVES To survey the frequency of use of indirect comparisons in systematic review s and evaluate the methods used in their analysis and interpretation . Also to identify alternative statistical approaches for the analysis of indirect comparisons , to assess the properties of different statistical methods used for performing indirect comparisons and to compare direct and indirect estimates of the same effects within review s. DATA SOURCES Electronic data bases . REVIEW METHODS The Data base of Abstract s of Review s of Effects ( DARE ) was search ed for systematic review s involving meta- analysis of r and omised controlled trials ( RCTs ) that reported both direct and indirect comparisons , or indirect comparisons alone . A systematic review of MEDLINE and other data bases was carried out to identify published methods for analysing indirect comparisons . Study design s were created using data from the International Stroke Trial . R and om sample s of patients receiving aspirin , heparin or placebo in 16 centres were used to create meta-analyses , with half of the trials comparing aspirin and placebo and half heparin and placebo . Methods for indirect comparisons were used to estimate the contrast between aspirin  and  heparin . The whole process was repeated 1000 times and the results were compared with direct comparisons and also theoretical results . Further detailed case studies comparing the results from both direct and indirect comparisons of the same effects were undertaken . RESULTS Of the review s identified through DARE , 31/327 ( 9.5 % ) included indirect comparisons . A further five review s including indirect comparisons were identified through electronic search ing . Few review s carried out a formal analysis and some based analysis on the naive addition of data from the treatment arms of interest . Few method ological papers were identified . Some valid approaches for aggregate data that could be applied using st and ard software were found : the adjusted indirect comparison , meta-regression and , for binary data only , multiple logistic regression ( fixed effect models only ) . Simulation studies showed that the naive method is liable to bias and also produces over-precise answers . Several methods provide correct answers if strong but unverifiable assumptions are fulfilled . Four times as many similarly sized trials are needed for the indirect approach to have the same power as directly r and omised comparisons . Detailed case studies comparing direct and indirect comparisons of the same effect show considerable statistical discrepancies , but the direction of such discrepancy is unpredictable . CONCLUSIONS Direct evidence from good- quality RCTs should be used wherever possible . Without this evidence , it may be necessary to look for indirect comparisons from RCTs . However , the results may be susceptible to bias . When making indirect comparisons within a systematic review , an adjusted indirect comparison method should ideally be used employing the r and om effects model . If both direct and indirect comparisons are possible within a review , it is recommended that these be done separately before considering whether to pool data . There is a need to evaluate methods for the analysis of indirect comparisons for continuous data and for empirical research into how different methods of indirect comparison perform in cases where there is a large treatment effect . Further study is needed into when it is appropriate to look at indirect comparisons and when to combine both direct and indirect comparisons . Research into how evidence from indirect comparisons compares to that from non-r and omised studies may also be warranted . Investigations using individual patient data from a meta- analysis of several RCTs using different protocol s and an evaluation of the impact of choosing different binary effect measures for the inverse variance method would also be useful PURPOSE We performed a study to determine whether postoperative mild chemotherapy to maintain the patient 's quality of life ( QOL ) and immunoactivity could also prolong survival . SUBJECT AND METHODS From December 1985 to July 1988 , 323 patients with completely resected primary non-small-cell lung cancer ( stage I to III ) were enrolled . The subjects were r and omized into three treatment groups , as follows : cisplatin ( CDDP ) 50 mg/m2 body surface , vindesine ( VDS ) 2 to 3 mg/kg body weight for three courses , and 1-year oral administration of tegafur ( FT ) plus uracil ( UFT ) 400 mg/kg body weight ( CVUft group , 115 patients ) ; 1-year oral administration of UFT 400 mg/kg body weight ( Uft group , 108 patients ) ; or surgical treatment only ( control group , 100 patients ) . RESULTS The overall 5-year survival rates were 60.6 % for the CVUft group and 64.1 % for the Uft group versus 49.0 % for the control group . The results of statistical testing were P = .053 ( log-rank test ) and P = .044 ( generalized Wilcoxon test ) among the three groups , P = .083 ( log-rank ) and P = .074 ( Wilcoxon ) between the CVUft and the control groups , and P = .022 ( log-rank ) and P = .019 ( Wilcoxon ) between the Uft and the control groups , which indicates higher survival rates in the CVUft and the Uft groups compared with the control group . A multivariate statistical analysis on prognostic factors using Cox 's proportional hazards model was performed with the following results : P = .037 , hazards ratio = 0.64 with a 95 % confidence interval ( CI ) of 0.42 to 0.97 ( control v CVUft group ) ; and P = .009 , hazards ratio = 0.55 with a 95 % CI of 0.36 to 0.86 ( control v Uft group ) . CONCLUSION Significantly favorable results were obtained in the CVUft and Uft groups compared with surgery alone . These data showed significant prognostic advantages in the postoperative adjuvant chemotherapy groups A prospect i ve r and omized trial ( the second cooperative study ) was conducted from July 1985 to December 1987 to investigate the benefits of postoperative adjuvant chemotherapy in patients for whom non-small cell lung cancer had been resected completely . Patients were r and omly assigned either to a chemotherapy group ( group A ) treated postoperatively with CDDP ( 66 mg/m2 x 1 ) , ADM ( 26 mg/m2 x 1 ) and UFT ( 8 mg/kg/day ) during 6 months , or to a control group ( group B ) which had undergone surgery only .  Three hundred and thirty-three resected cases were registered . Among them , 24 cases ( 7.2 % ) were excluded , because of incomplete resection ( 15 ) , pathologically benign tumour ( 3 ) , small cell lung cancer ( 2 ) and other factors ( 4 ) . Three hundred and nine cases were eligible : 155 cases in group A ( p-Stage I 93 , II 19 , III 43 ) and 154 in group B ( I 109 , II 10 , III 35 ) . The 5-year survival rate in group A was 61.8 % , and that in group B 58.1 % . The 5-year disease-free survival rate for each group was 61.8 % and 57.4 % , respectively . There were no significant differences in the 5-year survival between the two groups . However , since a significant difference was observed between the two groups regarding pathological lymph node metastasis ( pN ) , the prognostic factors were adjusted using Cox 's proportional hazard model . Thereafter the adjusted survival rate and disease-free survival rate for group A became significantly higher than for group B ( P = 0.044 and P = 0.036 , respectively ) . Thus , from these results , it is concluded that the role of surgery for non-small cell lung cancer still remains of primary importance , and postoperative adjuvant chemotherapy is effective to improve the results of surgery and prolong life of patients with non-small cell lung cancer This paper aims to explore the potential usefulness and limitations of indirect comparisons in evaluating the relative efficacy of interventions . From a systematic review of antimicrobial prophylaxis in colorectal surgery , we identified 11 sets of r and omized trials that can be used to compare antibiotics both directly and indirectly . The discrepancy between the direct and the indirect comparison is defined as the absolute value of difference in log odds ratio . The adjusted indirect comparison has the advantages that the prognostic factors of participants in different trials can be partially taken into account and more uncertainty be incorporated into its result by providing a wider confidence interval . However , considerable discrepancies exist between the direct and the adjusted indirect comparisons . When there is no direct comparison , the adjusted indirect method may be used to obtain some evidence about the relative efficacy of competing interventions , although such indirect results should be interpreted with great caution . Further empirical and method ologic research is needed to explore the validity and generalizability of the adjusted indirect comparison for evaluating different interventions Two hundred nine patients with completely resected stage III non-small-cell lung cancer were r and omized to receive postoperative cisplatin and vindesine chemotherapy or no further treatment . Before r and omization , patients were stratified by the histologic characteristics of their tumors ( squamous versus nonsquamous cell carcinoma ) . Prognostic variables such as histology , performance status , extent of operation , and tumor and nodal status of the eligible patients in chemotherapy ( n = 90 ) and control groups ( n = 91 ) were equally distributed . There was no statistically significant difference in disease-free and overall survival between the two groups . The 3-year disease-free survivals of the chemotherapy and control groups were 37 % and 42 % , respectively . The median survival times ( 5-year survival ) were 31 months ( 35 % ) in the chemotherapy group and 37 months ( 41 % ) in the control group . These was no different pattern in the first site of recurrence ( local versus systemic ) between the two groups . This study failed to demonstrate the therapeutic benefits of postoperative cisplatin and vindesine chemotherapy BACKGROUND Most studies of adjuvant chemotherapy , radiotherapy , or immunotherapy in non-small-cell lung cancer patients with complete surgical resection of disease have shown negative results . However , two studies of stage II and III disease by our Lung Cancer Study Group suggested an advantage to adjuvant therapy with cyclophosphamide , doxorubicin , and cisplatin ( CAP ) . PURPOSE Since neither of those studies had an untreated control , the Lung Cancer Study Group undertook a trial that included a control group and also offered the potential benefit of adjuvant therapy with CAP to patients with T1 , N1 or T2 , N0 ( stage I ) non-small-cell lung cancer . METHODS After complete resection , eligible patients with stage I disease were classified by known prognostic factors and r and omly assigned to receive or not to receive four courses of CAP at 3-week intervals beginning on day 30 after surgery . The CAP regimen consisted of 400 mg/m2 cyclophosphamide , 40 mg/m2 doxorubicin , and 60 mg/m2 cisplatin . Stratification by prognostic factors was as follows : histology ( squamous versus nonsquamous ) , white blood cell count before surgery ( > or = 9100/mm3 versus < 9100/mm3 ) , and Karnofsky performance status before surgery ( < or = 90 % versus 100 % ) . RESULTS Of the 269 patients entered in the study , 101 had recurrence and 127 have died . Mean time since r and omization is 6.4 years ; mean follow-up is 3.8 years . There were no differences in time to recurrence or overall survival ( not stratified by histology ) between the two groups , even when analyses were adjusted for prognostic variables . There was one treatment-related death on the CAP arm due to infection during neutropenia . Only 53 % of the eligible patients received all four courses of CAP , and only 57 % of such patients received all four cycles on time . In 74 % of the patients , the site of initial recurrence was distant . CONCLUSIONS The most likely explanations for the lack of efficacy of CAP are poor compliance to the protocol and relative inactivity of the regimen , compared with the activity of drug combinations used in more recent studies . On the basis of this trial , adjuvant therapy with CAP should not be recommended for patients with resected stage I lung cancer . IMPLICATION S Further trials to test adjuvant therapy are indicated , but investigators should use better antiemetics to improve patient compliance as well as more active chemotherapy regimens The purpose of this study was to evaluate the efficacy of adjuvant chemotherapy with three courses of cisplatin and vindesine , in comparison to observation only , for N2 non-small cell lung cancer that had been completely resected . Patients with pathologically demonstrated mediastinal lymph node metastasis ( N2 ) , who had undergone complete resection , were r and omized to observation or adjuvant chemotherapy ( cisplatin 80 mg/m2 on day 1 ; vindesine 3 mg/m2 on days 1 and 8 : x3 courses ) . Cycles started within 6 weeks after complete resection and were repeated every 4 weeks . This trial was terminated before accumulation of the planned numbers for registration because of a slow accrual rate . A total of 119 patients were r and omized ( 59 patients in the adjuvant arm and 60 with surgery alone ) . The median survival was 36 months for both groups . Postoperative cisplatin with vindesine chemotherapy was not shown to be efficacious in cases of completely resected N2 non-small cell lung cancer in this setting of timing , dose and agents studied Our objective was to clarify the efficacy of UFT administration after the complete resection of non-small cell lung cancer ( NSCLC ) at a single-center institution , avoiding the biases produced by interinstitutional differences . A total of 30 patients who underwent the complete resection of NSCLC at our hospital between 1987 and 2001 were r and omly assigned to a  control group or to a UFT group ( 400 mg/day for 2 years ) . Thirteen patients were assigned to the control group and 17 patients were assigned to the UFT group . The overall survival rate , disease-free survival rate , patient compliance and adverse effect of the UFT treatment were then analyzed . The overall survival and disease-free survival rates of the UFT group were superior to those of the control group . Four patients in the UFT group received medication for 24 months and 14 patients were treated for more than 3 months . No severe adverse effects were observed . Seven patients suffered a relapse in the control group . Two patients suffered a relapse in the UFT group , but the relapse occurred after the discontinuation of UFT administration . We conclude that the administration of UFT as an adjuvant therapy prolonged the overall survival and disease-free survival rates of patients after the resection of NSCLC in a small study performed at a single institution . Interinstitutional differences , particularly operating procedures , should be carefully considered when performing large multicenter clinical studies BACKGROUND In a previous phase 3 trial of adjuvant chemotherapy after resection of non-small-cell lung cancer , a combination of uracil and tegafur ( often referred to as UFT ) taken orally was shown to prolong survival . A subgroup analysis disclosed that most patients who benefited had pathological stage I adenocarcinoma . METHODS We r and omly assigned patients with completely resected pathological stage I adenocarcinoma of the lung to receive either oral uracil-tegafur ( 250 mg of tegafur per square meter of body-surface area per day ) for two years or no treatment . R and omization was performed with stratification according to the pathological tumor category ( T1 vs. T2 ) , sex , and age . The primary end point was overall survival . RESULTS From January 1994 through March 1997 , 999 patients were enrolled . Twenty patients were found to be ineligible and were excluded from the analysis after r and omization ; 491 patients were assigned to receive uracil-tegafur and 488 were assigned to observation . The median duration of follow-up for surviving patients was 73 months . The difference in overall survival between the two groups was statistically significant in favor of the uracil-tegafur group ( P=0.04 by a stratified log-rank test ) . Grade 3 toxic effects occurred in 10 of the 482 patients ( 2 percent ) who actually received uracil-tegafur . CONCLUSIONS Adjuvant chemotherapy with uracil-tegafur improves survival among patients with completely resected pathological stage I adenocarcinoma of the lung PURPOSE To evaluate the efficacy of postoperative adjuvant chemotherapy for completely resected p-stage I non-small cell lung cancer ( NSCLC ) . MATERIAL S AND METHODS Patients who underwent complete resection with lymph node dissection for p-stage I NSCLC ( T1N0 , T2N0 , adenocarcinoma or squamous cell carcinoma , were eligible . After surgery , 150 patients were stratified according to tumor size and histologic type , and then r and omly assigned to 1 of 3 groups ( 50 patients each group ) : surgery alone ( control group ) , surgery with chemotherapy ; PVU group ( 2 courses of cisplatin 80 mg/m2 , i.v . x 1 ( day 1 ) , vindesine 3 mg/m2 , i.v . x 1 ( days 1 and 8) and UFT 400 mg/day , p.o . for a period of 2 years ) , and UFT group ( UFT 400 mg/day , p.o . for 2 years ) . RESULTS The 5-year survival rates of the PVU group , the UFT group , and the control group were 87.9 , 67.7 , and 66.3 % , respectively . The difference in 5-year survival between the PVU group and the control group was statistically significant ( p = 0.045 , log rank ) . The 5-year disease-free survival rate of the PVU group ( 81.1 % ) was also significantly better than that of the control group ( 66.5 % ) ( p = 0.042 , log rank ) . According to multivariate analysis using Cox 's proportional hazard model , the only significantly positive factor on outcome was PVU chemotherapy after surgery . CONCLUSION Postoperative PVU chemotherapy is effective for Japanese patients with completely resected p-stage I NSCLC In 1989 , we began a multicenter study to evaluate the potential benefit of preoperative chemotherapy with cisplatin , ifosfamide and mitomycin over surgery alone in CT-visible N2 non-small-cell lung cancer . We present here a 7-year assessment of this r and omized trial . Sixty patients were r and omized to receive either surgery alone or three cycles of mitomycin 6 mg/m2 , ifosfamide 3 g/m2 and cisplatin 50 mg/m2 , given intravenously on day 1 of each cycle at 3-week intervals and followed by surgery . All patients received thoracic irradiation after surgery . The resected tumors were evaluated for the presence of K-ras gene point mutations . Treatment arms were well-balanced in characteristics such as gender , age , histology , and tumor size . Mediastinoscopy and /or mediastinotomy ( Chamberlain procedure ) with a biopsy was performed in all patients with N2 stage detected by CT scan of the chest ( 83 % of the patients in the preresectional chemotherapy arm and 63 % of those in the surgery arm ) . In eight of the 25 patients ( 32 % ) who had mediastinoscopy in the preresectional chemotherapy arm , the initially positive mediastinal lymph nodes were downstaged . For the 30 patients who received preresectional chemotherapy , overall median survival was 22 months ( 95 % CI , 13.4 30.6 ) . Of the 30 patients who received surgery alone , overall median survival was 10 months ( 95 % CI , 7.4 - 12.6 ; P = 0.005 by the log rank test ) . Up date d survival data reveals a plateau in the preresectional chemotherapy group , and this still significant long-term survival benefit prompts us to hypothesize that even with short-term preresectional chemotherapy , the natural history of still resectable CT-visible N2 non-small cell lung cancer is favorably altered . The results of our study mirror the long-term survival recently reported in the MD And erson r and omized study The role of neoadjuvant chemotherapy in stage IIIa non-small cell lung cancer remains undefined . Since 1987 , 27 patients with non-small cell lung cancer , all with histologically confirmed metastases to the ipsilateral mediastinal lymph nodes , have been enrolled in an ongoing prospect i ve , r and omized trial at our institution . Thirteen patients have been r and omized to preoperative etoposide-platinum ( EP ) chemotherapy-surgery-postoperative EP , and 14 other patients have been r and omized to surgery-postoperative mediastinal irradiation ( SRT ) .  Both groups are similar in sex , age , weight loss , tumor location , preoperative pulmonary function , physiologic grade , and tumor histology . Eight of the 13 EP patients have responded as evidence d by a 50 % or greater radiographic tumor shrinkage after two cycles . Complete tumor and nodal resection rates were similar : 11/13 EP patients versus 12/14 SRT patients . There was no operative mortality for the 27 patients . Median potential follow-up is 29.9 months for the EP group and 34.9 months for the SRT group . Preliminary results suggest a trend toward increased survival time for the EP group ( median , 28.7 months ) versus the SRT group ( median , 15.6 months ) ( p2 = 0.095 ) . Eleven of 12 resected SRT patients have had recurrence versus 8 of 11 resected EP patients . Time to recurrence reveals no significant differences between the two groups but a trend toward increased disease-free interval in the EP group ( 12.7 months versus 5.8 months , EP versus SRT ) . This interim analysis demonstrates the feasibility of such a trial ; however , despite the trends , definitive conclusions await further accrual and study maturation BACKGROUND To explore the clinicopathological changes of non-small cell lung cancer tissues after neoadjuvant chemotherapy with MVP ( MMC+VDS+DDP ) regimen and its concordance with clinical evaluation , and to study the clinical value of neoadjuvant chemotherapy . METHODS A total of 84 patients with NSCLC were r and omized into combinated therapy  group ( 42 cases ) and surgical group ( 42 cases ) . The combinated therapy group were given MVP regimen for 2 cycles before operation and 2 - 4 cycles after operation , however , the surgical group only received surgical treatment . The efficacy of preoperative chemotherapy were determined by pathologic examination under light microscope and electron microscope and clinical evaluation . RESULTS Combinated therapy group showed various degrees of degeneration and necrosis of tumor cells , which was not found in surgical group . The overall response rate of neoadjuvant chemotherapy was 59.5 % ( 25/42 ) by both pathological and clinical evaluation . The coincidence ratio of the two evaluation methods was 71.4 % ( Kappa value=0.407,P < 0.01 ) . Between the two groups , there was a significant difference in total survival rate ( P=0.047 ) . And further analysis showed that survival rate was remarkably different in patients with stage III between the two groups ( P=0.037 ) , but not in those with stage I and II ( P > 0.05 ) . CONCLUSIONS Degeneration and necrosis with fibrosis are the main pathological phenotypes of the primary lesion after induction chemotherapy , which can be showed by clinical evaluation to chemotherapy efficacy . The preoperative and postoperative adjuvant chemotherapy may be benefical to patients with stage-III NSCLC PURPOSE The aims of this study were to assess the effect of adjuvant chemotherapy on overall survival , disease-free survival , and relapse pattern , as well as its toxicity in patients who underwent radical surgery for non-small-cell lung cancer ( NSCLC ) . PATIENTS AND METHODS One hundred ten patients with T1 - 3N0 ( World Health Organization [ WHO ] 1981 ) NSCLC underwent radical surgery during the period of 1982 through 1987 . After surgery , the patients were r and omized to receive adjuvant chemotherapy ( n = 54 ) ( cyclophosphamide 400 mg/m2 , doxorubicin 40 mg/m2 , and cisplatin 40 mg/m2 [ CAP ] for six cycles ) or no active treatment ( n = 56 ) . RESULTS After 10 years from the start of the study , 61 % of patients were alive in the chemotherapy group and 48 % were alive in the control group ( P = .050 ) . Seventeen patients ( 31 % ) in the CAP group and 27 patients ( 48 % ) in the control group had a recurrence during the follow-up period ( P = .01 ) . The 5-year survival rate was 67 % in the chemotherapy group and was 56 % in the control group ( P = .050 ) . The patients in the chemotherapy group who completed the planned treatment had a slightly better 5-year survival than those whose chemotherapy was discontinued ( 72.5 % v 50.3 % ; P = .15 ) . Chemotherapy-related gastrointestinal toxicity grade 3 to 4 ( WHO ) occurred in 63 % and was the main reason why patients refused further planned therapy . CONCLUSION Our results suggest that patients with NSCLC at pathologic stage I who have undergone radical surgery benefit from adjuvant chemotherapy OBJECTIVE Many phase II trials have shown that preoperative chemotherapy for lung cancer is feasible but associated with postoperative morbidity and mortality . However , little is known about the effect of preoperative chemotherapy on surgical stress and postoperative complications associated with surgical intervention . We evaluated the effect of preoperative chemotherapy on perioperative inflammatory cytokine production as a surgical stress marker . METHODS The study group comprised 38 patients undergoing anatomical lung resection and mediastinal nodal dissection for clinical stage IB/II non-small cell lung cancer during the period October 2001-December 2003 . Nineteen patients received a single cycle of cisplatin ( 80 mg/m(2  ) )  and docetaxel ( 60 mg/m(2 ) ) chemotherapy prior to surgery  ( neoadjuvant group ) , and 19 patients underwent surgery without any previous chemotherapy ( control group ) . White blood cell and neutrophil counts and serum concentrations of C-reactive protein ( CRP ) , interleukin-6 ( IL-6 ) , and granulocyte colony-stimulating factor ( GCSF ) were determined before surgery and on postoperative days 1 and 3 . Postoperative complications were review ed . Differences were assessed by repeated analysis of variance . RESULTS Serum concentrations of IL-6 and GCSF rose significantly on postoperative days 1 and 3 in the neoadjuvant group in comparison to concentrations in the control group , but white blood cell count , neutrophil count , and CRP did not differ between the groups . No major complication occurred in either group . CONCLUSIONS A single cycle of cisplatin and docetaxel chemotherapy followed by surgery can exacerbate overproduction of inflammatory cytokines during the perioperative period in lung cancer patients
INTRODUCTION A large number of trials have evaluated the efficacy of postoperative chemotherapy on survival after resection for lung cancer , and a smaller number have evaluated preoperative chemotherapy on survival for potentially resectable lung cancer , but no direct comparison has yet been published comparing the two approaches .