- Email: [email protected]
A randomized trial of cisplatin plus paclitaxel versus cisplatin plus teniposide in advanced non-small cell lung cancer
Current Perspectives in the Treatment of Non-Small Cell Lung Cancer
A randomized trial of cisplatin plus paclitaxel versus cisplatin plus teniposide in advanced non-small cell lung cancer Giuseppe Giaccone, Ted A.W. Splinter, Maria Diaz-Puente, Nice van Zandwijk, Andrea Ardizzoni, Jan van Meerbeeck, Tarek Sahmoud. EORTC Lung Cancer
Piet E. Postmus, Giorgio Scagliotti, Channa Debruyne, Cooperative Group,
332 patients with advanced non-small cell lung cancer (NSCLC) were randomized to receive one of two cisplatinbased chemotherapy regimens: A) paclitaxel 175 mg/m* given by 3-hour infusion followed by cisplatin 80 mg/m2, on day 1; or B) cisplatin 80 mg/m2, on day 1, followed by teniposide 100 mg/m2 given on days 1, 3, and 5. Cycles were repeated every 3 weeks. Patient accrual was from July 1993 to February 1996; 13 patients were ineligible. Overall the two arms (166 patients randomized in each arm) were well balanced for major prognostic factors: approximately 70% of patients were male, had lost ~5% body weight, 90% had performance status 0 or 1, 50% had adenocarcinoma, and 60% had stage IV disease. Hematological toxicity was more severe and more frequent in the arm B than in arm A: in the arm 8, approximately 50% of patients developed grade 3-4 leukopenia, almost 80% developed grade 3-4 neutropenia, and almost 40% severe thrombocytopenia. Because of the severe myelosuppression, a substantial number of patients also developed treatment-related
145
infections. In contrast, the A arm had relatively mild hematological toxicity, with 18%, 54%, and 3% grade 3-4 leukopenia, neutropenia and thrombocytopenia, respectively. Mainly because of myelosuppression there were more treatment delays and dose reductions in the standard arm than in the experimental arm. The non-hematological side effects were mainly represented by alopecia and nausea and vomiting in both arms. A slightly higher incidence of peripheral neurotoxicity and arthralgia/myalgia were reported in the paclitaxel arm. Peripheral neurotoxicity did not represent a serious problem in patients who received a maximum of 6 cycles of chemotherapy. Low and similar frequencies of severe hypersensitivity reactions and cardiac toxicity were observed in both arms of the study. Responses were largely partial in both arms: they were 46% and 28% for arm A and B, respectively, on over 250 patients whose response was extramurally reviewed. Extramural radiological response evaluation is still being completed and these numbers may slightly change in the final analysis. So far, survival appears to be comparable in the two arms, being the median survival time in the range of 9 months in boths arms. The required number of events has been recently achieved, and a final analysis is being carried out; this will include quality of life assessment. Quality of life assessment was carried out in selected centers. An improved quality of life was observed in arm A during the treatment period.
A randomized trial of cisplatin plus paclitaxel versus cisplatin plus teniposide in advanced non-small cell lung cancer Giuseppe Giaccone, Ted A.W. Splinter, Maria Diaz-Puente, Nice van Zandwijk, Andrea Ardizzoni, Jan van Meerbeeck, Tarek Sahmoud. EORTC Lung Cancer
Piet E. Postmus, Giorgio Scagliotti, Channa Debruyne, Cooperative Group,
332 patients with advanced non-small cell lung cancer (NSCLC) were randomized to receive one of two cisplatinbased chemotherapy regimens: A) paclitaxel 175 mg/m* given by 3-hour infusion followed by cisplatin 80 mg/m2, on day 1; or B) cisplatin 80 mg/m2, on day 1, followed by teniposide 100 mg/m2 given on days 1, 3, and 5. Cycles were repeated every 3 weeks. Patient accrual was from July 1993 to February 1996; 13 patients were ineligible. Overall the two arms (166 patients randomized in each arm) were well balanced for major prognostic factors: approximately 70% of patients were male, had lost ~5% body weight, 90% had performance status 0 or 1, 50% had adenocarcinoma, and 60% had stage IV disease. Hematological toxicity was more severe and more frequent in the arm B than in arm A: in the arm 8, approximately 50% of patients developed grade 3-4 leukopenia, almost 80% developed grade 3-4 neutropenia, and almost 40% severe thrombocytopenia. Because of the severe myelosuppression, a substantial number of patients also developed treatment-related
145
infections. In contrast, the A arm had relatively mild hematological toxicity, with 18%, 54%, and 3% grade 3-4 leukopenia, neutropenia and thrombocytopenia, respectively. Mainly because of myelosuppression there were more treatment delays and dose reductions in the standard arm than in the experimental arm. The non-hematological side effects were mainly represented by alopecia and nausea and vomiting in both arms. A slightly higher incidence of peripheral neurotoxicity and arthralgia/myalgia were reported in the paclitaxel arm. Peripheral neurotoxicity did not represent a serious problem in patients who received a maximum of 6 cycles of chemotherapy. Low and similar frequencies of severe hypersensitivity reactions and cardiac toxicity were observed in both arms of the study. Responses were largely partial in both arms: they were 46% and 28% for arm A and B, respectively, on over 250 patients whose response was extramurally reviewed. Extramural radiological response evaluation is still being completed and these numbers may slightly change in the final analysis. So far, survival appears to be comparable in the two arms, being the median survival time in the range of 9 months in boths arms. The required number of events has been recently achieved, and a final analysis is being carried out; this will include quality of life assessment. Quality of life assessment was carried out in selected centers. An improved quality of life was observed in arm A during the treatment period.