Between June 1993 and September 1999, 217 patients with small cell lung cancer (SCLC) entered three sequential phase II trials evaluating novel paclitaxel-containing three-drug combination chemotherapy regimens. Patients with limited- or extensive-stage SCLC, no previous treatment, and Eastern Cooperative Oncology Group performance status 0 to 2 were eligible. Trials 1 and 2 evaluated the combination of paclitaxel, carboplatin, and etoposide; in the second trial, doses of paclitaxel and carboplatin were higher than in the first trial. Trial 3 evaluated the combination of paclitaxel, carboplatin, and topotecan. Patients with limited-stage disease received radiation therapy to the primary tumor site and mediastinum, beginning concurrently with the third course of chemotherapy. All patients received four courses of chemotherapy, administered at 21-day intervals. All three regimens were highly active and produced high response rates in both limited- and extensive-stage SCLC. Median survivals for regimens 1, 2, and 3 in extensive-stage patients were 8, 10, and 8.5 months, respectively. Median survivals in limited- stage disease were 16, 20, and 15 months, respectively. Although definitive comparisons of these regimens cannot be made on the basis of sequential trials, the higher-dose paclitaxel/carboplatin/etoposide regimen seemed superior; with this regimen, 4-year survival in limited-stage disease was 23%. Paclitaxel-containing three-drug regimens, as evaluated in these three phase II trials, were feasible and highly active in the first-line treatment of SCLC. Randomized trials will be necessary to definitively evaluate the efficacy of these regimens as compared with traditional platinum/etoposide combinations. Semin Oncol 28 (suppl 4):43-47.

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