Paclitaxel and carboplatin in the treatment of small-cell lung cancer patients resistant to cyclophosphamide, doxorubicin, and etoposide: A non-cross-resistant schedule

Purpose: To evaluate the efficacy of paclitaxel and carboplatin (PC) in sma ll-cell lung cancer (SCLC) patients resistant to cyclophasphamide, doxorubi cin, and etoposide (CDE). Patients and Methods: We performed a phase II study with PC in SCLC patient s who relapsed within 3 months after first-line treatment with CDE. Paclita xel administration (175 mg/m(2) by a 3-hour intravenous infusion) was follo wed by a 30-minute infusion of carboplatin (area under the curve 7;Chatelut formula) once every 3 weeks for five cycles. Dexamethasone, clemastine, an d ranitidine were standard premedication before every cycle. Results: Included were 35 patients (median age, 59 years; 16 with limited d isease and 19 with extensive disease; Eastern Cooperative Oncology Group pe rformance status of less than or equal to 1; median time off treatment 6 we eks) who were previously treated with CDE (n = 33), oral etoposide (n = 2), and reinduction CDE (n = 15); only one patient herd received three CDE tre atments of five cycles. The CDE regimen was followed by local thoracic radi otherapy in seven patients. Hematologic toxicity of grade 3 or 4, for leuko penia was 27% and 6%, for thrombocytopenia 21% and 13%, and for anemia 17% and 0%, respectively, for a total of 132 cycles. Two patients had neutropen ic fever; no toxic death occurred. Nonhematologic toxicity was paresthesia CTC grade 3, diarrhea grade 4, and myalgia grade 3 in one patient each. Rev ersible paresthesia (CTC grade 1 and 2) in toes and fingers was reported in 69% of patients. Thirty-four patients were assessable for response: comple te response in two patients, partial response in 23 patients, stable diseas e in eight patients, and progressive disease in one patient (response rate, 73.5%; 95% confidence interval, 59% to 88%). One patient was found to have atypical carcinoid at pathologic review and was excluded. Median time ta p rogression wets 21 weeks (range, 3 to 40 weeks). Median survival was 31 wee ks (range, 6 to 112 weeks). One-year survival was 9%. Conclusion: Second-line PC in CDE-resistant SCLC patients yields a high res ponse rate and seems non-cross-resistant to CDE. Toxicity was mild in these poor-prognosis patients. (C) 1999 by American Society of Clinical Oncology .