Dose-intensive weekly alternating chemotherapy for patients with small cell lung cancer: randomized trial, can it improve survival of patients with good prognostic factors?

We conducted a randomized trial of dose-intensive weekly alternating chemotherapy (CAV/PE-W) and standard alternating chemotherapy (CAV/PE) in small cell lung cancer (SCLC) patients with good prognostic factors. A total of 76 patients with SCLC was randomized. The CAV/PE-W consisted of 4 alternating cycles of cyclophosphamide: 500 mg/m2, doxorubicin: 30 mg/m2, and vincristine: 1 mg/m2 (day 1) and cisplatin: 50 mg/m2 (day 8) and etoposide: 75 mg/m2 (days 8 and 9). The CAV/PE consisted of 2 alternating cycles of cyclophosphamide: 800 mg/m2, doxorubicin: 50 mg/m2, and vincristine: 1.4 mg/m2 (day 1), cisplatin: 100 mg/m2 (day 22) and etoposide: 100 mg/m2 (days 22, 23 and 24). Eligibility criteria were no prior therapy, no active concomitant malignancy, ECOG PS of 0 or 1, age < or =75, adequate hematologic functions and no brain metastasis. The complete response (CR) rate for CAV/PE-W (14/38, 36.8%) was significantly higher than that for CAV/PE (6/38, 15.8%, chi2; p=0. 032). However, the response rate in patients on CAV/PE-W (36/38, 94. 7%) was not significantly higher than the rate for CAV/PE (31/38, 81. 6%, chi2; p=0.076). Progression-free survival for patients on CAV/PE-W was significantly longer than that of patients on CAV/PE (41.4 weeks vs. 21.3 weeks, log-rank; p=0.0007, generalized Wilcoxon; p=0.0034) as was overall median survival (67.0 weeks vs. 51.2 weeks, log-rank; p=0.028). Actual dose-intensity of CAV/PE-W was 1.74 times that of CAV/PE. Hematological toxicities were equally frequent and G-CSF contributes to treatment efficacy by allowing administration of dose-intensive chemotherapy. The CAV/PE-W achieved a higher CR rate and longer survival, than the CAV/PE.