A phase I study of gemcitabine/cisplatin/etoposide in the treatment of small-cell lung cancer

Purpose: To define the maximum tolerated dose and toxicity of combined cisp latin, etoposide, and gemcitabine in patients with small-cell lung cancer. Methods: We undertook a phase I study in patients with either extensive sma ll-cell lung cancer with or without prior chemotherapy, or limited disease who had progressed or recurred despite prior treatment. Patients received c isplatin 75 mg/m(2) IV day I, etoposide 50-100 mg/m(2) IV day 1 followed by oral administration of 50-100 mg/m(2) days 2-5, and gemcitabine at either 800 or 1000 mg/m(2) IV days I and 8, on a 3 weekly cycle. Results: We treat ed 20 patients, 14 at the 800 mg/m(2) gemcitabine dose level, and six at th e 1000 mg/m(2) dose level. The protocol initially used an etoposide dose of 100 mg/m(2) etoposide daily (IV day 1 and orally days 2-5), but the first two patients died of septic complications. With reduction of the etoposide dose to 50 mg/m(2) daily x 5, the regimen was well tolerated. At this etopo side dose, neutropenia, mucositis, and gastrointestinal toxicity occurred i n one patient at each of the two gemcitabine dose levels. In addition, one patient receiving gemcitabine at the 1000 mg/m(2) level experienced a possi ble allergic reaction. The overall response rate was 54%. Patients on gemci tabine at the 800 mg/m(2) level who had not received prior chemotherapy had the highest response rate, at 75%. Conclusion: The recommended phase II do ses for this regimen are cisplatin 75 mg/m(2) IV day 1, etoposide 50 mg/m(2 ) IV day 1 and orally days 2-5, and gemcitabine 800 mg/m(2) IV days 1 and 8 . Future trials should further examine the optimal relative doses and sched ule of gemcitabine and etoposide. (C) 1998 Elsevier Science Ireland Ltd. Al l rights reserved.