A randomised phase II trial of docetaxel vs docetaxel and irinotecan in patients with stage IIIb–IV non-small-cell lung cancer who failed first-line treatment Docetaxel (D) versus docetaxel plus gemcitabine (DG) for second-line treatment of non-small cell lung cancer (NSCLC): Results of a JCOG randomized trial (JCOG0104). Erlotinib in previously treated non-small-cell lung cancer. Multi-institutional randomized phase II trial of gefitinib for previously treated patients with advanced non-small-cell lung cancer (The IDEAL 1 Trial) [corrected]. Randomized phase III trial of docetaxel versus vinorelbine or ifosfamide in patients with advanced non-small-cell lung cancer previously treated with platinum-containing chemotherapy regimens. The TAX 320 Non-Small Cell Lung Cancer Study Group. Prospective randomized trial of docetaxel versus best supportive care in patients with non-small-cell lung cancer previously treated with platinum-based chemotherapy. Efficacy of gefitinib, an inhibitor of the epidermal growth factor receptor tyrosine kinase, in symptomatic patients with non-small cell lung cancer: a randomized trial. A randomised clinical trial of two docetaxel regimens (weekly vs 3 week) in the second-line treatment of non-small-cell lung cancer. The DISTAL 01 study Randomised, multicentre phase II study assessing two doses of docetaxel (75 or 100 mg/m2) as second-line monotherapy for non-small-cell lung cancer. Irinotecan plus gemcitabine vs irinotecan for the second-line treatment of patients with advanced non-small-cell lung cancer pretreated with docetaxel and cisplatin: a multicentre, randomised, phase II study Comparison of docetaxel and docetaxel-irinotecan combination as second-line chemotherapy in advanced non-small-cell lung cancer: a randomized phase II trial. Single-agent versus combination chemotherapy in advanced non-small-cell lung cancer: the cancer and leukemia group B (study 9730). Phase II randomized trial of irinotecan/docetaxel (ID) or irinotecan/gemcitabine (IG) with or without celecoxib (CBX) in 2nd-line treatment of non-small-cell lung cancer (NSCLC). Phase III comparative study of high-dose cisplatin versus a combination of paclitaxel and cisplatin in patients with advanced non-small-cell lung cancer. Phase III randomized trial comparing three platinum-based doublets in advanced non-small-cell lung cancer. Erlotinib in lung cancer - molecular and clinical predictors of outcome. Phase I trial of docetaxel administered by weekly infusion in patients with advanced refractory cancer. Phase I and pharmacologic study of OSI-774, an epidermal growth factor receptor tyrosine kinase inhibitor, in patients with advanced solid malignancies. Randomized, multinational, phase III study of docetaxel plus platinum combinations versus vinorelbine plus cisplatin for advanced non-small-cell lung cancer: the TAX 326 study group. Clinically meaningful improvement in symptoms and quality of life for patients with non-small-cell lung cancer receiving gefitinib in a randomized controlled trial. Selective oral epidermal growth factor receptor tyrosine kinase inhibitor ZD1839 is generally well-tolerated and has activity in non-small-cell lung cancer and other solid tumors: results of a phase I trial. Gefitinib plus best supportive care in previously treated patients with refractory advanced non-small-cell lung cancer: results from a randomised, placebo-controlled, multicentre study (Iressa Survival Evaluation in Lung Cancer) Phase III study of second-line chemotherapy for advanced non-small-cell lung cancer with weekly compared with 3-weekly docetaxel. Active-control equivalence trials and antihypertensive agents. Randomized phase III trial of pemetrexed versus docetaxel in patients with non-small-cell lung cancer previously treated with chemotherapy. Post study docetaxel in non-small cell lung cancer (NSCLC) patients after discontinuation from a randomized phase III trial of pemetrexed versus docetaxel: An exploratory analysis. Phase II randomised trial comparing docetaxel given every 3 weeks with weekly schedule as second-line therapy in patients with advanced non-small-cell lung cancer (NSCLC).
Response rate and toxicity of second-line therapy with docetaxel ( 75 mg m−2 ) or docetaxel , irinotecan , and lenogastrim ( 60 mg m−2 , 200 mg m−2 , and 150 μg m−2 day−1 , respectively ) were compared in 108 patients with stage IIIb – IV non-small-cell lung cancer . Addition of irinotecan to docetaxel does not improve response rate , and increases gastrointestinal toxicity 7034 Background : D is now the st and ard second-line treatment for NSCLC patients based upon improved survival and quality of life in two phase III studies . DG has been also promising in several phase II trials in second-line setting . In order to evaluate whether combination regimen of DG provides better overall survival than D in patients with previously treated NSCLC , we conducted a r and omized trial . METHODS Eligibility included pathologically or cytologically proven NSCLC , stage IV or IIIB , one prior platinum-based regimen chemotherapy , performance status 0 or 1 , 20 - 75 years old . Patients were r and omized to receive either D ( 60 mg/m2 , day 1 ) or DG ( D 60 mg/m2 , day 8 , G 800 mg/m2 , days 1 , 8) , repeated every 21 days until disease progression . RESULTS 65 patients were accrued in each arm between Jan. 2002 and Apr. 2003 ( planned ; 142 per arm ) ; one was ineligible due to stage IIIA . This trial was terminated early with unexpected high incidence of interstitial lung disease ( ILD ) and 3 treatment related death ( 5 % ) due to ILD only in DG arm , which were identified by Adverse Event Reporting system . DG compared with D patients experienced similar grade 3 - 4 neutropenia ( DG 70 % , D 75 % ) , grade 2 - 4 nausea ( 17 % , 15 % ) , anorexia ( 20 % , 23 % ) , constipation ( 21 % , 30 % ) , alopecia ( 23 % , 24 % ) , febrile neutropenia ( 15 % , 25 % ) , but more dyspnea ( 23 % , 14 % ) and ILD ( 21 % , 2 % ) . There was no baseline factor identified for predicting ILD . The hazard ratio ( HR ) for overall survival was 0.89 ( 95 % CI 0.52 , 1.55 , logrank p = 0.69 ) in favor of DG . Median survival was 11.3 ( DG ) and 10.1 months ( D ) . One-year survival rate was 47 % and 38 % . The HR for progression free survival ( PFS ) was 0.68 ( 95 % CI 0.46 , 0.99 , p = 0.04 ) . Median PFS was 3.1 ( DG ) and 2.1 ( D ) months . CONCLUSIONS The combination of D and G may be too toxic regimen due to high risk of ILD for previously treated patients . D alone is still considered to be the st and ard second-line treatment for NSCLC . No significant financial relationships to disclose BACKGROUND We conducted a r and omized , placebo-controlled , double-blind trial to determine whether the epidermal growth factor receptor inhibitor erlotinib prolongs survival in non-small-cell lung cancer after the failure of first-line or second-line chemotherapy . METHODS Patients with stage IIIB or IV non-small-cell lung cancer , with performance status from 0 to 3 , were eligible if they had received one or two prior chemotherapy regimens .  The patients were stratified according to center , performance status , response to prior chemotherapy , number of prior regimens , and prior platinum-based therapy and were r and omly assigned in a 2:1 ratio to receive oral erlotinib , at a dose of 150 mg daily , or placebo . RESULTS The median age of the 731 patients who underwent r and omization was 61.4 years ; 49 percent had received two prior chemotherapy regimens , and 93 percent had received platinum-based chemotherapy .  The response rate was 8.9 percent in the erlotinib group and less than 1 percent in the placebo group ( P<0.001 ) ; the median duration of the response was 7.9 months and 3.7 months , respectively . Progression-free survival was 2.2 months and 1.8 months , respectively ( hazard ratio , 0.61 , adjusted for stratification categories ; P<0.001 ) . Overall survival was 6.7 months and 4.7 months , respectively ( hazard ratio , 0.70 ; P<0.001 ) , in favor of erlotinib . Five percent of patients discontinued erlotinib because of toxic effects . CONCLUSIONS Erlotinib can prolong survival in patients with non-small-cell lung cancer after first-line or second-line chemotherapy PURPOSE To evaluate the efficacy and tolerability of two doses of gefitinib ( Iressa [ ZD1839 ] ; AstraZeneca , Wilmington , DE ) , a novel epidermal growth factor receptor tyrosine kinase inhibitor , in patients with pretreated advanced non-small-cell lung cancer ( NSCLC ) . PATIENTS AND METHODS This was a r and omized , double-blind , parallel-group , multicenter phase II trial . Two hundred ten patients with advanced NSCLC who were previously treated with one or two chemotherapy regimens ( at least one containing platinum )  were r and omly assigned to receive either 250-mg or 500-mg oral doses of gefitinib once daily . RESULTS Efficacy was similar for the 250- and 500-mg/d groups . Objective tumor response rates were 18.4 % ( 95 % confidence interval [ CI ] , 11.5 to 27.3 ) and 19.0 % ( 95 % CI , 12.1 to 27.9 ) ; among evaluable patients , symptom improvement rates were 40.3 % ( 95 % CI , 28.5 to 53.0 ) and 37.0 % ( 95 % CI , 26.0 to 49.1 ) ; median progression-free survival times were 2.7 and 2.8 months ; and median overall survival times were 7.6 and 8.0 months , respectively . Symptom improvements were recorded for 69.2 % ( 250 mg/d ) and 85.7 % ( 500 mg/d ) of patients with a tumor response . Adverse events ( AEs ) at both dose levels were generally mild ( grade 1 or 2 ) and consisted mainly of skin reactions and diarrhea . Drug-related toxicities were more frequent in the higher-dose group . Withdrawal due to drug-related AEs was 1.9 % and 9.4 % for patients receiving gefitinib 250 and 500 mg/d , respectively . CONCLUSION Gefitinib showed clinical ly meaningful antitumor activity and provided symptom relief as second- and third-line treatment in these patients . At 250 mg/d , gefitinib had a favorable AE profile . Gefitinib 250 mg/d is an important , novel treatment option for patients with pretreated advanced NSCLC [ corrected PURPOSE To confirm the promising phase II results of docetaxel monotherapy , this phase III trial was conducted of chemotherapy for patients with advanced non-small-cell lung cancer ( NSCLC ) who had previously failed platinum-containing chemotherapy . PATIENTS AND METHODS A total of 373 patients were r and omized to receive either docetaxel 100 mg/m(2 ) ( D100 ) or 75 mg/m(2 ) ( D75 ) versus a control regimen of vinorelbine or ifosfamide ( V/I ) . The three treatment groups were well-balanced for key patient characteristics . RESULTS Overall response rates were 10.8 % with D100 and 6.7 % with D75 , each significantly higher than the 0.8 % response with V/I ( P = .001 and P = .036 , respectively ) . Patients who received docetaxel had a longer time to progression ( P = .046 , by log-rank test ) and a greater progression-free survival at 26 weeks ( P = .005 , by chi(2 ) test ) . Although overall survival was not significantly different between the three groups , the 1-year survival was significantly greater with D75 than with the control treatment ( 32 % v 19 % ; P = .025 , by chi(2 ) test ) . Prior exposure to paclitaxel did not decrease the likelihood of response to docetaxel , nor did it impact survival . There was a trend toward greater efficacy in patients whose disease was platinum-resistant rather than platinum-refractory and in patients with performance status of 0 or 1 versus 2 . Toxicity was greatest with D100 , but the D75 arm was well-tolerated . CONCLUSION This first r and omized trial in this setting demonstrates that D75 every 3 weeks can offer clinical ly meaningful benefit to patients with advanced NSCLC whose disease has relapsed or progressed after platinum-based chemotherapy PURPOSE To evaluate whether treatment with single-agent docetaxel would result in longer survival than would best supportive care in patients with non-small-cell lung cancer who had previously been treated with platinum-based chemotherapy .  Secondary end points included assessment of response ( docetaxel arm only ) , toxicity , and quality of life . PATIENTS AND METHODS Patients with performance statuses of 0 to 2 and stage IIIB/IV non-small-cell lung cancer with either measurable or evaluable lesions were eligible for entry onto the study if they had undergone one or more platinum-based chemotherapy regimens and if they had adequate hematology and biochemistry parameters . They were excluded if they had symptomatic brain metastases or if they had previously been treated with paclitaxel .  Patients were stratified by performance status and best response to cisplatin chemotherapy and were then r and omized to treatment with docetaxel 100 mg/m(2 ) ( 49 patients ) or 75 mg/m(2 ) ( 55 patients ) or best supportive care . Patients in both arms were assessed every 3 weeks . RESULTS One hundred four patients ( 103 of whom were eligible for entry onto the study ) were well balanced for prognostic factors . Of 84 patients with measurable lesions , six ( 7 . 1 % ) achieved partial responses ( three patients at each dose level ) . Time to progression was longer for docetaxel patients than for best supportive care patients ( 10.6 v 6.7 weeks , respectively ; P < .001 ) , as was median survival ( 7.0 v 4.6 months ; log-rank test , P = .047 ) . The difference was more significant for docetaxel 75 mg/m(2 ) patients , compared with corresponding best supportive care patients ( 7.5 v 4.6 months ; log-rank test , P = .010 ; 1-year survival , 37 % v 11 % ; chi(2 ) test , P = .003 ) . Febrile neutropenia occurred in 11 patients treated with docetaxel 100 mg/m(2 ) , three of whom died , and in one patient treated with docetaxel 75 mg/m(2 ) . Grade 3 or 4 nonhematologic toxicity , with the exception of diarrhea , occurred at a similar rate in both the docetaxel and best supportive care groups . CONCLUSION Treatment with docetaxel is associated with significant prolongation of survival , and at a dose of 75 mg/m(2 ) , the benefits of docetaxel therapy outweigh the risks CONTEXT More persons in the United States die from non-small cell lung cancer ( NSCLC ) than from breast , colorectal , and prostate cancer combined . In pre clinical testing , oral gefitinib inhibited the growth of NSCLC tumors that express the epidermal growth factor receptor ( EGFR ) , a mediator of cell signaling , and phase 1 trials have demonstrated that a fraction of patients with NSCLC progressing after chemotherapy experience both a decrease in lung cancer symptoms and radiographic tumor shrinkages with gefitinib . OBJECTIVE To assess differences in symptomatic and radiographic response among patients with NSCLC receiving 250-mg and 500-mg daily doses of gefitinib .  DESIGN , SETTING , AND PATIENTS Double-blind , r and omized phase 2 trial conducted from November 2000 to April 2001 in 30 US academic and community oncology centers . Patients ( N = 221 ) had either stage IIIB or IV NSCLC for which they had received at least 2 chemotherapy regimens . INTERVENTION Daily oral gefitinib , either 500 mg ( administered as two 250-mg gefitinib tablets ) or 250 mg ( administered as one 250-mg gefitinib tablet and 1 matching placebo ) . MAIN OUTCOME MEASURES Improvement of NSCLC symptoms ( 2-point or greater increase in score on the summed lung cancer subscale of the Functional Assessment of Cancer Therapy-Lung [ FACT-L ] instrument ) and tumor regression ( > 50 % decrease in lesion size on imaging studies ) . RESULTS Of 221 patients enrolled , 216 received gefitinib as r and omized . Symptoms of NSCLC improved in 43 % ( 95 % confidence interval [ CI ] , 33%-53 % ) of patients receiving 250 mg of gefitinib and in 35 % ( 95 % CI , 26%-45 % ) of patients receiving 500 mg . These benefits were observed within 3 weeks in 75 % of patients . Partial radiographic responses occurred in 12 % ( 95 % CI , 6%-20 % ) of individuals receiving 250 mg of gefitinib and in 9 % ( 95 % CI , 4%-16 % ) of those receiving 500 mg . Symptoms improved in 96 % of patients with partial radiographic responses . The overall survival at 1 year was 25 % . There were no significant differences between the 250-mg and 500-mg doses in rates of symptom improvement ( P = .26 ) , radiographic tumor regression ( P = .51 ) , and projected 1-year survival ( P = .54 ) . The 500-mg dose was associated more frequently with transient acne-like rash ( P = .04 ) and diarrhea ( P = .006 ) . CONCLUSIONS Gefitinib , a well-tolerated oral EGFR-tyrosine kinase inhibitor , improved disease-related symptoms and induced radiographic tumor regressions in patients with NSCLC persisting after chemotherapy Docetaxel ( 75 mg m−2 3-weekly ) is st and ard second-line treatment in advanced non-small-cell lung cancer ( NSCLC ) with significant toxicity . To verify whether a weekly schedule ( 33.3 mg m−2 for 6 weeks ) improved quality of life ( QoL ) , a phase III study was performed with 220 advanced NSCLC patients , ⩽75 years , ECOG PS ⩽2 . QoL was assessed by EORTC question naires and the Daily Diary Card ( DDC ) . No difference was found in global QoL scores at 3 weeks . Pain , cough and hair loss significantly favoured the weekly schedule , while diarrhoea was worse . DDC analysis showed that loss of appetite and overall condition were significantly worse in the 3-week arm in the first week , while nausea and loss of appetite were more severe in the weekly arm in the third week . Response rate and survival were similar , hazard ratio of death in the weekly arm being 1.04 ( 95 % CI 0.77–1.39 ) . A 3-weekly docetaxel was more toxic for leukopenia , neutropenia , febrile neutropenia and hair loss ; any grade 3–4 haematologic toxicity was significantly more frequent in the st and ard arm ( 25 vs 6 % ) . The weekly schedule could be preferred for patients c and i date to receive docetaxel as second-line treatment for advanced NSCLC , because of some QoL advantages , lower toxicity and no evidence of strikingly different effect on survival BACKGROUND The survival benefit associated with first-line chemotherapy in advanced lung cancer led to the need for second-line chemotherapy . Docetaxel ( Taxotere ) has proven efficacy in both setting s. This study evaluated the safety and efficacy of two doses of docetaxel in patients with non-small-cell lung cancer who had failed first-line platinum-based chemotherapy . PATIENTS AND METHODS In total , 182 patients from 24 French centres were r and omised and treated with either docetaxel 75 mg/m(2 ) ( arm A ) or 100 mg/m(2 ) ( arm B ) every 3 weeks . Baseline characteristics were well balanced , except more patients in arm A had metastatic disease ( 91.4 % versus 78.7 % ) and therefore the median number of sites involved for arm A was three compared with two for arm B. RESULTS Median time to treatment failure was 1.34 months [ 95 % confidence interval ( CI ) 1.28 - 1.64 ] for arm A and 1.64 months ( 95 % CI 1.34 - 2.62 ) for arm B. Median overall survival was 4.7 months ( 95 % CI 3.8 - 5.9 ) for arm A versus 6.7 months ( 95 % CI 4.8 - 7.1 ) for arm B. According to a blinded expert panel , disease control was achieved in 35 ( 43.8 % ) patients in arm A and 39 ( 49.4 % ) patients in arm B. More patients in arm B experienced grade 3 - 4 neutropenia ( B : 72.7 % versus A : 44.0 % ) , asthenia ( B : 20.2 % versus A : 10.8 % ) and infection ( B : 6.7 % versus A : 2.2 % ) . Three treatment-related deaths were reported in each arm . CONCLUSIONS The optimal docetaxel dosage in this second-line setting is 75 mg/m(2 ) , as it has a more favourable safety profile and on balance a similar efficacy to the 100 mg/m(2 ) dose To compare irinotecan (CPT-11)+gemcitabine vs CPT-11 alone as second-line treatment for patients with advanced non-small cell lung cancer ( NSCLC ) progressing after docetaxel – cisplatinum-based therapy . A total of 147 evaluable , pretreated patients , with NSCLC , received either gemcitabine ( 1000 mg m−2 , days 1 and 8)+CPT-11 ( 300 mg m−2 , day 8) ( Group A , n=76 ) or CPT-11 ( 300 mg m−2 , day 1 ) ( Group B , n=71 ) , every 3 weeks . All patients were evaluable for response and toxicity . The objective response rate was 18.4 % ( 95 % CI : 9.71–27.14 % ) and 4.2 % ( 95 % CI : 0–8.90 % ) ( P=0.009 ) for groups A and B , respectively . No significant differences between the two groups in terms of the median duration of response , time to tumour progression , overall survival and 1-year survival were observed . The CPT-11/gemcitabine regimen significantly improved the patients ' quality of life ( ‘ general mood today ’ ( P=0.014 ) , ‘ coughing ’ ( P=0.003 ) and ‘ intensity of symptoms ’ ( P=0.034 ) ) compared with CPT-11 . More cycles had to be delayed ( P=0.001 ) and required prophylactic growth factor support ( P=0.001 ) in Group A than B. Three ( 3.9 % ) patients in Group A and eight ( 11.3 % ) in Group B developed febrile neutropenia ( P=0.09 ) ; one patient died of sepsis in each group . Three additional ( Group A , n=1 ; Group B , n=2 ) treatment-related deaths were observed . Grade 3–4 haematologic toxicity was comparable in the two groups except anaemia ( P=0.03 in favour of CPT-11 ) . Other nonhaematologic toxicities were mild and similar in the two groups . CPT-11+gemcitabine result ed in a higher response rate and better control of disease-related symptoms than CPT-11 alone , but without any improvement in the overall survival BACKGROUND The aim of this study was to evaluate whether docetaxel ( taxotere ) treatment with or without irinotecan improved patient outcomes with similar toxicity in recurrent non-small-cell lung cancer ( NSCLC ) . PATIENTS AND METHODS Patients with recurrent platinum-refractory NSCLC with Eastern Cooperative Oncology Group performance status of 0 - 2 were r and omized to either docetaxel 30 mg/m(2 ) and irinotecan 60 mg/m(2 ) ( days 1 and 8) or docetaxel 75 mg/m(2 ) ( day 1 ) , both administered every 3 weeks . RESULTS A total of 130 patients were r and omized . The response rate ( RR ) ( 20 % versus 14 % ) , overall survival ( 6.5 months versus 6.4 months ) and 1-year survival ( 37 % versus 34 % ) were similar in the combination and docetaxel arms , respectively . The combination arm demonstrated a longer time to tumor progression ( TTP ) ( 5.6 versus 4.8 months ; P=0.065 ) . Grade 3 - 4 neutropenia and anemia were similar in the combination and docetaxel arms . Grade s 3 - 4 non-hematological toxicity ( except diarrhea ) was mild and was similar in the two groups . Grade 3 - 4 thrombocytopenia ( 17 % versus 6 % ; P=0.04 ) and diarrhea ( 12 % versus 3 % ; P=0.05 ) occurred more frequently in the combination arm . CONCLUSIONS The administration of irinotecan with docetaxel in platinum-refractory NSCLC prolonged TTP , but did not improve significantly RR , median survival or 1-year survival .  Second-line docetaxel monotherapy offers significant and reproducible efficacy in platinum-refractory NSCLC PURPOSE We compared the efficacy of combination chemotherapy versus single-agent therapy in patients with advanced non-small-cell lung cancer . PATIENTS AND METHODS A total of 561 eligible patients were r and omly assigned to receive paclitaxel alone or in combination with carboplatin . RESULTS The response rate was 17 % in the paclitaxel arm and 30 % in the carboplatin-paclitaxel arm ( P < .0001 ) . Median failure-free survival was 2.5 months in the paclitaxel arm and 4.6 months in the carboplatin-paclitaxel arm ( P = .0002 ) . Median survival times were 6.7 months ( 95 % CI , 5.8 to 7.8 ) and 8.8 months ( 95 % CI , 8.0 to 9.9 ) , and 1-year survival rates were 32 % ( 95 % CI , 27 % to 38 % ) , and 37 % ( 95 % CI , 32 % to 43 % ) , respectively . The overall survival distributions were not statistically different : hazard ratio = 0.91 ( 95 % CI , 0.77 to 1.17 ; P = .25 ) . Hematological toxicity and nausea were more frequent in the combination arm , but febrile neutropenia and toxic deaths were equally low in both arms . There was no significant survival difference  in elderly patients . Performance status 2 patients treated with combination chemotherapy had a better survival rate than those treated with single-agent therapy ( P = .019 ) . CONCLUSION Combination chemotherapy improves response rate and failure-free survival compared with single-agent therapy , but there was no statistically significant difference in the primary end point of overall survival . The results in elderly patients were similar to younger patients . Performance status 2 patients had a superior outcome when treated with combination chemotherapy 7137 Background : Current 2nd-line treatment options for pts with advanced stage NSCLC are limited . New , more effective , and less toxic agents/combinations are thus needed for treating NSCLC in the 2nd-line setting . This r and omized , parallel , open-label , multicenter , phase II trial was design ed to assess the efficacy/safety of the combinations ID and IG , and biomodulation with CBX , in pts with advanced NSCLC who failed 1 prior chemotherapy regimen . METHODS Men/women aged ≥18 years were r and omized by 2x2 design to CBX 400 mg BID or none concurrent with chemotherapy until progressive disease , and to ID ( irinotecan 60 mg/m2 and docetaxel 35 mg/m2 ) or IG ( irinotecan 100 mg/m2 and gemcitabine 1000 mg/m2 ) administered on days 1 and 8 every 21 days until disease progression . RESULTS 133 pts were enrolled , with 131 receiving ≥1 dose and evaluable for safety : median age 64 years ; gender 80 men/53 women ; race 107 Caucasian/14 Black/12 other ; and baseline ECOG 0 = 44 , and 1 = 89 . All treatment arms were balanced regarding baseline demographics , disease sites , and laboratory parameters . Efficacy ( n = 97)/toxicity ( n = 131 ) are tabulated by ID vs IG and CBX vs none . One nontreatment-related sudden death due to cardiac arrest occurred on day 7 . CONCLUSIONS The results suggest that both ID and IG combination therapies are well-tolerated and efficacious 2nd-line regimens for patients with advanced NSCLC .  CBX is tolerable when combined with these regimens ; however , it did not enhance efficacy and may have interacted to increase hematologic toxicity . This will be formally tested when the data is mature . [ Figure : see text ] [ Table : see text ] PURPOSE New effective chemotherapy is needed to improve the outcome of patients with advanced non-small-cell lung cancer ( NSCLC ) .  Paclitaxel administered as a single agent or in combination with cisplatin has been shown to be a potentially new useful agent for the treatment of NSCLC . PATIENTS AND METHODS Between January 1995 and April 1996 , 414 patients with stage IIIB or IV NSCLC were r and omized to received either a control arm of high-dose cisplatin ( 100 mg/m(2 ) ) or a combination of paclitaxel ( 175 mg/m(2 ) , 3-hour infusion ) and cisplatin ( 80 mg/m(2 ) ) every 21 days . RESULTS Compared with the cisplatin-only arm , there was a 9 % improvement ( 95 % confidence interval , 0 % to 19 % ) in overall response rate for the paclitaxel/cisplatin arm ( 17 % v 26 % , respectively ; P=.028 ) . Median time to progression was 2.7 and 4.1 months in the control and paclitaxel/cisplatin arm , respectively ( P=.026 ) . The study , however , failed to show a significant improvement in median survival for the paclitaxel/cisplatin arm ( 8.6 months in the control arm v 8.1 months in the paclitaxel/cisplatin arm , P=.862 ) . There was more hematotoxicity , peripheral neuropathy , and arthralgia/myalgia on the paclitaxel/cisplatin arm , whereas the high-dose cisplatin arm produced more ototoxicity , nausea , vomiting , and nephrotoxicity . Quality of life ( QOL ) was similar overall between the two arms . CONCLUSION This large r and omized phase III trial failed to show a significant improvement in survival for the paclitaxel/cisplatin combination compared with high-dose cisplatin in patients with advanced NSCLC . However , the paclitaxel/cisplatin combination did produce a better clinical response , result ing in an increased time to progression while providing a similar QOL PURPOSE To evaluate whether two commonly used newer platinum-based regimens offer any advantage over vinorelbine-cisplatin ( reference regimen ) in response rate for patients with advanced non-small-cell lung cancer ( NSCLC ) . PATIENTS AND METHODS Chemotherapy-naive patients were r and omized to receive gemcitabine 1,250 mg/m(2 ) days 1 and 8 plus cisplatin 75 mg/m(2 ) day 2 every 21 days ( GC arm ) , or paclitaxel 225 mg/m(2 ) ( 3-hour infusion ) then carboplatin ( area under the concentration-time curve of 6 mg/mL x min ) , both on day 1 every 21 days ( PCb arm ) , or vinorelbine 25 mg/m(2)/wk for 12 weeks then every other week plus cisplatin 100 mg/m(2 ) day 1 every 28 days ( VC arm ) . RESULTS Six hundred twelve patients were r and omized to treatment ( 205 GC , 204 PCb , and 203 VC ) . Overall response rates for the GC ( 30 % ) and PCb ( 32 % ) arms were not significantly different from that of the VC arm ( 30 % ) . There were no differences in overall survival , time to disease progression , or time to treatment failure . Median survival for the GC , PCb , and VC groups was 9.8 , 9.9 , and 9.5 months , respectively . Neutropenia was significantly higher on the VC arm ( GC 17 % or PCb 35 % v VC 43 % of cycles , P < .001 ) , as was thrombocytopenia on the GC arm ( GC 16 % v VC 0.1 % of cycles , P < .001 ) . Alopecia and peripheral neurotoxicity were most common on the PCb arm , as was nausea/vomiting on the VC arm ( P < .05 ) . CONCLUSION Efficacy end points were not significantly different between experimental and reference arms , although toxicities showed differences . These findings suggest that chemotherapy in NSCLC has reached a therapeutic plateau BACKGROUND A clinical trial that compared erlotinib with a placebo for non-small-cell lung cancer demonstrated a survival benefit for erlotinib . We used tumor-biopsy sample s from participants in this trial to investigate whether responsiveness to erlotinib and its impact on survival were associated with expression by the tumor of epidermal growth factor receptor ( EGFR ) and EGFR gene amplification and mutations . METHODS EGFR expression was evaluated immunohistochemically in non-small-cell lung cancer specimens from 325 of 731 patients in the trial ; 197 sample s were analyzed for EGFR mutations ; and 221 sample s were analyzed for the number of EGFR genes . RESULTS In univariate analyses , survival was longer in the erlotinib group than in the placebo group when EGFR was expressed ( hazard ratio for death , 0.68 ; P=0.02 ) or there was a high number of copies of EGFR ( hazard ratio , 0.44 ; P=0.008 ) . In multivariate analyses , adenocarcinoma ( P=0.01 ) , never having smoked ( P<0.001 ) , and expression of EGFR ( P=0.03 ) were associated with an objective response . In multivariate analysis , survival after treatment with erlotinib was not influenced by the status of EGFR expression , the number of EGFR copies , or EGFR mutation . CONCLUSIONS Among patients with non-small-cell lung cancer who receive erlotinib  , the presence of an EGFR mutation may increase responsiveness to the agent , but it is not indicative of a survival benefit PURPOSE Docetaxel is a highly active antineoplastic agent ; however , grade IV leukopenia occurs in the large majority of patients treated with a dose of 100 mg/m2 every 3 weeks . Recent experience with weekly paclitaxel has demonstrated a bone marrow-sparing effect when a weekly administration schedule is used . We investigated a weekly schedule of docetaxel in an attempt to alter the toxicity profile and improve the therapeutic index . PATIENTS AND METHODS Thirty-eight patients with advanced , refractory malignancy entered this phase I trial between October 1996 and June 1997 .  Docetaxel was administered weekly for 6 consecutive weeks , followed by 2 weeks without treatment . Sequential cohorts of patients were treated at the following dose levels : 20 , 25 , 30 , 36 , 43 , and 52 mg/m2 . Patients were reevaluated after one course ( 8 weeks ) ; patients with objective response or stable disease continued treatment for a maximum of four courses or until disease progression . RESULTS Thirty-five patients completed at least one course of therapy . Myelosuppression was not a dose-limiting toxicity ( DLT ) at any of the doses tested . Only five episodes of grade III leukopenia occurred ( 14 % of patients , 2 % of doses ) , and no grade IV leukopenia was produced . No grade III or IV thrombocytopenia or anemia was observed . Grade III fatigue and asthenia were observed in all three patients treated at 52 mg/m2/wk and in two of 10 at 43 mg/m2/wk . Other grade III toxicity included acral erythema ( n = 1 ) , neuropathy ( n = 1 ) , peripheral edema ( n = 1 ) , and diarrhea ( n = 1 ) . The DLTs of this docetaxel schedule are fatigue and asthenia . Although the maximum-tolerated dose by definition of this study was 43 mg/m2/wk , we selected 36 mg/m2/wk for ongoing phase II studies . CONCLUSION The toxicity profile of docetaxel is markedly altered when the drug is administered by a weekly schedule . Myelosuppression is mild and uncommon . Fatigue and asthenia are the DLTs ; other nonhematologic toxicities , which included peripheral edema and neuropathy , are uncommon , and the arthralgia/myalgia syndrome was not observed . Weekly administration of docetaxel may provide a better tolerated , efficacious use of this drug ; further investigation of weekly docetaxel as a single agent and in combination regimens is warranted PURPOSE To assess the feasibility of administering OSI-774 , to recommend a dose on a protracted , continuous daily schedule , to characterize its pharmacokinetic behavior , and to acquire preliminary evidence of anticancer activity . PATIENTS AND METHODS Patients with advanced solid malignancies were treated with escalating doses of OSI-774 in three study parts ( A to C ) to evaluate progressively longer treatment intervals . Part A patients received OSI-774 25 to 100 mg once daily , for 3 days each week , for 3 weeks every 4 weeks . Part B patients received OSI-774 doses ranging from 50 to 200 mg given once daily for 3 weeks every 4 weeks to establish the maximum tolerated dose ( MTD ) . In part C , patients received this MTD on a continuous , uninterrupted schedule . The pharmacokinetics of OSI-774 and its O-demethylated metabolite , OSI-420 , were characterized . RESULTS Forty patients received a total of 123 28-day courses of OSI-774 .  No severe toxicities precluded dose escalation of OSI-774 from 25 to 100 mg/d in part A. In part B , the incidence of severe diarrhea and /or cutaneous toxicity was unacceptably high at OSI-774 doses exceeding 150 mg/d . Uninterrupted , daily administration of OSI-774 150 mg/d represented the MTD on a protracted daily schedule . The pharmacokinetics of OSI-774 were dose independent ; repetitive daily treatment did not result in drug accumulation ( at 150 mg/d [ average ] : minimum steady-state plasma concentration , 1.20 + /- 0.62 microg/mL ; clearance rate , 6.33 + /- 6.41 L/h ; elimination half-life , 24.4 + /- 14.6 hours ; volume of distribution , 136 . 4 + /- 93.1 L ; area under the plasma concentration-time curve for OSI-420 relative to OSI-774 , 0.12 + /- 0.12 microg/h/mL ) . CONCLUSION The recommended dose for disease-directed studies of OSI-774 administered orally on a daily , continuous , uninterrupted schedule is 150 mg/d . OSI-774 was well tolerated , and several patients with epidermoid malignancies demonstrated either antitumor activity or relatively long periods of stable disease . The precise contribution of OSI-774 to these effects is not known PURPOSE To investigate whether docetaxel plus platinum regimens improve survival and affect quality of life ( QoL ) in advanced non-small-cell lung cancer ( NSCLC ) compared with vinorelbine plus cisplatin as first-line chemotherapy . PATIENTS AND METHODS Patients ( n = 1,218 ) with stage IIIB to IV NSCLC were r and omly assigned to receive docetaxel 75 mg/m2 and cisplatin 75 mg/m2 every 3 weeks ( DC ) ; docetaxel 75 mg/m2 and carboplatin area under the curve of 6 mg/mL * min every 3 weeks ( DCb ) ; or vinorelbine 25 mg/m2/wk and cisplatin 100 mg/m2 every 4 weeks ( VC ) . RESULTS Patients treated with DC had a median survival of 11.3 v 10.1 months for VC-treated patients ( P = .044 ; hazard ratio , 1.183 [ 97.2 % confidence interval , 0.989 to 1.416 ] ) . The 2-year survival rate was 21 % for DC-treated patients and 14 % for VC-treated patients . Overall response rate was 31.6 % for DC-treated patients v 24.5 % for VC-treated patients ( P = .029 ) . Median survival ( 9.4 v 9.9 months [ for VC ] ; P = .657 ; hazard ratio , 1.048 [ 97.2 confidence interval , 0.877 to 1.253 ] ) and response ( 23.9 % ) with DCb were similar to those results for VC . Neutropenia , thrombocytopenia , infection , and febrile neutropenia were similar with all three regimens . Grade 3 to 4 anemia , nausea , and vomiting were more common ( P < .01 ) with VC than with DC or DCb . Patients treated with either docetaxel regimen had consistently improved QoL compared with VC-treated patients , who experienced deterioration in QoL. CONCLUSION DC result ed in a more favorable overall response and survival rate than VC . Both DC and DCb were better tolerated and provided patients with consistently improved QoL compared with VC . These findings demonstrate that a docetaxel plus platinum combination is an effective treatment option with a favorable therapeutic index for first-line treatment of advanced or metastatic NSCLC PURPOSE Evaluation of disease-related symptom improvement rate by the Lung Cancer Subscale ( LCS ) of the Functional Assessment of Cancer Therapy-Lung ( FACT-L ) question naire was a co primary end point of the pivotal phase II trial of gefitinib ( Iressa ; AstraZeneca , Wilmington , DE ) conducted in the United States . This report includes the results of analyses exploring the relationship between weekly LCS scores and radiographic response and survival , as well as detailed protocol -specified analysis of symptom and quality -of-life data . PATIENTS AND METHODS In this trial , 216 symptomatic patients with advanced non-small-cell lung cancer ( NSCLC ) who had at least two prior chemotherapy regimens received gefitinib 250 or 500 mg/d  . Disease-related symptoms were assessed weekly and quality of life was assessed monthly by LCS and FACT-L , respectively . Results Symptom improvement was rapid and correlated with tumor response and survival . At the recommended gefitinib dose of 250 mg/d , median overall survival times were 13.6 and 4.6 months for patients with and without symptom improvement , respectively , and 9.7 months for patients with symptom improvement without tumor response . Among patients with stable disease or disease progression , those with symptom improvement had significantly better overall survival than those without improvement . At 250 mg/d , 30 % of patients showed a quality -of-life improvement that was correlated with tumor response . CONCLUSION This triadic analysis of response , survival , and symptom data supports the hypothesis that tumor response and symptom response are related and that each predicts survival . Among these NSCLC patients treated with gefitinib , symptom improvement was complementary to and , for most patients , preceded evidence of radiographic regression PURPOSE To investigate safety , tolerability , dose-related pharmacologic properties , and pharmacodynamics of ZD1839 ( gefinitib , Iressa ; AstraZeneca Pharmacueticals , Wilmington , DE ) , an epidermal growth factor receptor ( EGFR ) tyrosine kinase inhibitor , in patients with solid tumor types known to express or highly express EGFR . METHODS This was an open-label , phase I , dose escalation safety/tolerability trial of oral ZD1839 ( 150 to 1,000 mg/d ) , administered once daily for 28-continuous-day cycles until disease progression or undue toxicity . RESULTS Of 71 ( 69 assessable for safety ; 58 for efficacy ) patients at seven dose levels , most had non-small-cell lung ( n = 39 ) or head and neck ( n = 18 ) cancer , and 68 of 71 patients received prior cancer therapy ( two or more regimens in 54 patients [ 78 % ] ) . Diarrhea and rash , the primary dose-limiting toxicities ( DLTs ) , occurred at 800 mg . Frequent treatment-related grade 1/2 adverse events were diarrhea ( 55 % ) , asthenia ( 44 % ) , and acne-like follicular rash ( 46 % ) . At doses > or= 800 mg , 45 % of patients required dose reductions . No increased or cumulative toxicity was observed over 250 patient-months of exposure . Pharmacokinetic analysis showed that steady-state occurred by day 7 , interpatient exposure was more variable than intrapatient exposure , and variability of exposure did not change with dose . One patient experienced a partial response , but antitumor activity manifested mainly as prolonged stable disease ( 45 % of patients > or= 3 months , 22 % > or= 6 months , and 7.2 % > or= 1 year ) . No relationship between dose , response , or duration on study was observed . CONCLUSION Rash and diarrhea , generally mild and tolerable at doses < or= 600 mg/d , were DLTs at 800 mg/d ( maximum-tolerated dose ) . Antitumor activity was observed at all doses . Pharmacokinetic analyses confirmed suitability of once-daily oral dosing BACKGROUND This placebo-controlled phase III study investigated the effect on survival of gefitinib as second-line or third-line treatment for patients with locally advanced or metastatic non-small-cell lung cancer . METHODS 1692 patients who were refractory to or intolerant of their latest chemotherapy regimen were r and omly assigned in a ratio of two to one either gefitinib ( 250 mg/day ) or placebo , plus best supportive care . The primary endpoint was survival in the overall population of patients and those with adenocarcinoma . The primary analysis of the population for survival was by intention to treat . This study has been su bmi tted for registration with Clinical Trials.gov , number 1839IL/709 . FINDINGS 1129 patients were assigned gefitinib and 563 placebo .  At median follow-up of 7.2 months , median survival did not differ significantly between the groups in the overall population ( 5.6 months for gefitinib and 5.1 months for placebo ; hazard ratio 0.89 [ 95 % CI 0.77 - 1.02 ] , p=0.087 ) or among the 812 patients with adenocarcinoma ( 6.3 months vs 5.4 months ; 0.84 [ 0.68 - 1.03 ] , p=0.089 ) . Preplanned subgroup analyses showed significantly longer survival in the gefitinib group than the placebo group for never-smokers ( n=375 ; 0.67 [ 0.49 - 0.92 ] , p=0.012 ; median survival 8.9 vs 6.1 months ) and patients of Asian origin ( n=342 ; 0.66 [ 0.48 - 0.91 ] , p=0.01 ; median survival 9.5 vs 5.5 months ) . Gefitinib was well tolerated , as in previous studies . INTERPRETATION Treatment with gefitinib was not associated with significant improvement in survival in either co primary population . There was pronounced heterogeneity in survival outcomes between groups of patients , with some evidence of benefit among never-smokers and patients of Asian origin PURPOSE A phase III study to determine whether a weekly docetaxel schedule improves the therapeutic index compared with the classic 3-weekly schedule . PATIENTS AND METHODS Patients with stage IIIB-IV non-small-cell lung cancer ( NSCLC ) were r and omly assigned to docetaxel 75 mg/m2 on day 1 every 3 weeks ( 3-weekly ) and 35 mg/m2 on days 1 , 8 , and 15 ( weekly ) for < or = eight cycles . End points included survival ( primary ) , toxicity , and response . RESULTS Of 215 patients enrolled , 208 ( 103 in the 3-weekly arm and 105 in the weekly arm ) were assessable for response . At baseline , 24.5 % of patients ( 51 out of 208 ) had received prior paclitaxel therapy and 43.3 % of patients ( 90 out of 208 ) had been progression-free for more than 3 months after first-line therapy . After 12 months ' follow-up , median survival was 6.3 months ( 95 % CI , 4.68 to 7.84 months ) with 3-weekly docetaxel and 9.2 months ( 95 % CI , 5.83 to 12.59 months ) with weekly docetaxel ( P = .07 ) after a median of four ( range , one to eight ) and two ( range , one to eight ) treatment cycles , respectively . Overall , response rates were 12.6 % v 10.5 % with 3-weekly versus weekly docetaxel . Significantly fewer patients reported grade 3 to 4 toxicities with weekly docetaxel versus 3-weekly docetaxel ( P < or = .05 ) . There were significantly lower rates of grade 3 to 4 anemia ( P < or = .05 ) , leucopenia ( P < .0001 ) , and neutropenia ( P < or = .001 ) with weekly versus 3-weekly treatment . No grade 3 to 4 thrombocytopenia or mucositis was reported . CONCLUSION Weekly docetaxel 35 mg/m2 demonstrated similar efficacy and better tolerability than st and ard 3-weekly docetaxel 75 mg/m2 and can be recommended as a feasible alternative second-line treatment option for patients with advanced NSCLC PURPOSE To identify method ological features that affect the validity of conclusions drawn from active-control equivalence trials and to apply these criteria to recently published trials comparing antihypertensive agents from different classes . METHODS St and ard method ological criteria for r and omized clinical trials and six additional method ological features that affect the validity of active-control equivalence trials were applied to four recently published large trials that compared different antihypertensive classes and that concluded that their results showed equivalence . RESULTS All four of these trials fulfilled st and ard criteria for r and omized trials . However , none fulfilled all of the six additional method ological criteria that affect the validity of active-control equivalence trials , one fulfilled five criteria , two fulfilled two criteria , and one failed to fulfill any of the criteria . CONCLUSION St and ard method ological criteria for evaluating superiority trials are inadequate for the interpretation of active-control equivalence trials . The method ological criteria outlined in this article for judging the validity of active-control equivalence trials are not specific to antihypertensive trials and may be applied to trials that test a wide variety of interventions PURPOSE To compare the efficacy and toxicity of pemetrexed versus docetaxel in patients with advanced non-small-cell lung cancer ( NSCLC ) previously treated with chemotherapy . PATIENTS AND METHODS Eligible patients had a performance status 0 to 2 , previous treatment with one prior chemotherapy regimen for advanced NSCLC , and adequate organ function . Patients received pemetrexed 500 mg/m(2 ) intravenously ( i.v . ) day 1 with vitamin B(12 ) , folic acid , and dexamethasone or docetaxel 75 mg/m(2 ) i.v . day 1 with dexamethasone every 21 days . The primary end point was overall survival . RESULTS Five hundred seventy-one patients were r and omly assigned . Overall response rates were 9.1 % and 8.8 % ( analysis of variance P = .105 ) for pemetrexed and docetaxel , respectively . Median progression-free survival was 2.9 months for each arm , and median survival time was 8.3 versus 7.9 months ( P = not significant ) for pemetrexed and docetaxel , respectively . The 1-year survival rate for each arm was 29.7 % . Patients receiving docetaxel were more likely to have grade 3 or 4 neutropenia ( 40.2 % v 5.3 % ; P < .001 ) , febrile neutropenia ( 12.7 % v 1.9 % ; P < .001 ) , neutropenia with infections ( 3.3 % v 0.0 % ; P = .004 ) , hospitalizations for neutropenic fever ( 13.4 % v 1.5 % ; P < .001 ) , hospitalizations due to other drug related adverse events ( 10.5 % v 6.4 % ; P = .092 ) , use of granulocyte colony-stimulating factor support ( 19.2 % v 2.6 % , P < .001 ) and all grade alopecia ( 37.7 % v 6.4 % ; P < .001 ) compared with patients receiving pemetrexed . CONCLUSION Treatment with pemetrexed result ed in clinical ly equivalent efficacy outcomes , but with significantly fewer side effects compared with docetaxel in the second-line treatment of patients with advanced NSCLC and should be considered a st and ard treatment option for second-line NSCLC when available 7135 Background : For NSCLC pts with good performance status , second-line treatment with chemotherapy improves survival . Routine administration of second-line chemotherapy has increased the percentage of pts receiving third-line therapy . In a recent multicenter , r and omized , phase III comparison of pemetrexed versus docetaxel in previously treated pts with advanced NSCLC , survival time with pemetrexed therapy was similar to docetaxel ( median 8.3 vs 7.9 months ) . Over 40 % of pts in the study received third-line chemotherapy post study . Of those pts treated with pemetrexed , 32 % received docetaxel post study . The aim of this exploratory analysis was to evaluate if the survival observed in the pemetrexed arm was due to a cross-over effect of post study chemotherapy with docetaxel as opposed to other post study chemotherapy agents . METHODS Survival analyses were performed using Kaplan-Meier method in 3 subsets of patients with respect to their post study treatment . RESULTS In total , 541 pts received either pemetrexed or docetaxel ; 48 % of pts in the pemetrexed arm and 39 % of pts in the docetaxel arm received third line chemotherapy . In the pemetrexed arm , the median survival of pts who received post study docetaxel was 1 month less ( 9.6 ) than the median survival of pts who received other post study chemotherapy agents ( 10.6 ; p=.219 ) . CONCLUSIONS In the original study , overall survival was similar for both treatment arms . In this evaluation , these results provide no evidence that the overall survival observed in the pemetrexed arm with third-line post study docetaxel is different than that observed in the pts who received other third-line post study chemotherapy agents . [ Figure : see text ] [ Table : see text ] BACKGROUND Taxotere ( docetaxel ) at the dose of 75 mg/m(2 ) every 3 weeks is a st and ard therapy for pretreated non-small-cell lung cancer ( NSCLC ) . The aim of this study was to evaluate the safety profile of two schedules of docetaxel administration ( every 3 weeks versus weekly ) in patients with pretreated NSCLC . PATIENTS AND METHODS From February 2000 to February 2001 , 125 patients with locally advanced or metastatic NSCLC were r and omised after failure of a previous platinum-based regimen to receive either docetaxel 75 mg/m(2 ) administered every 3 weeks ( Dq3w )  or docetaxel 40 mg/m(2 ) given weekly for 6 weeks followed by 2 weeks of rest ( Dqw ) . Safety evaluations focused on grade 3 - 4 neutropenia , febrile neutropenia , nausea-vomiting and asthenia . RESULTS Patients ' characteristics were well balanced between arms . The most common National Cancer Institute Common Toxicity Criteria ( NCI-CTC ) grade 3 - 4 toxicity was neutropenia , which occurred in 48.4 % of Dq3w patients versus 15.9 % of Dqw patients ( P=0.001 ) . In addition , febrile neutropenia were observed in 6.5 % of patients in Dq3w versus 0 % in Dqw . Grade 3 - 4 asthenia was more frequent in Dqw . Other non-haematological toxicities were very rare . Regarding efficacy , there was a trend towards a better disease control rate in Dq3w : 32.2 % versus 25.4 % in Dqw . Median time to progression and survival were rather similar in both arms , respectively : 2.1 months ( range 2 - 3.2 ) and 5.8 months ( range 4.0 - 7.0 ) in Dq3w and 1.8 months ( range 1.6 - 2.3 ) and 5.5 months ( range 3.7 - 6.6 ) in Dqw . CONCLUSIONS While both schedules had a favourable safety profile , a significant lower rate of severe neutropenia was observed in the weekly arm . Both regimens had similar efficacy . The weekly regimen could be considered as a good alternative for patients at risk of severe neutropenia
PURPOSE This clinical practice guideline , based on a systematic review , evaluates second-line or subsequent therapy for patients with recurrent or progressive non-small cell lung cancer .