Phase I/II trial of gemcitabine plus cisplatin and etoposide in patients with small-cell lung cancer

Objective: The objectives of this phase I/II study were to define the maximum tolerated dose (MTD), safety, and activity of cisplatin, etoposide, and gemcitabine (PEG) in the treatment of previously untreated patients with small-cell lung cancer (SCLC). Patients and Methods: Chemonaive patients received fixed doses of gemcitabine (1000 mg/m² on days 1 and 8) and cisplatin (70 mg/m² on day 2) and escalating doses of etoposide (starting dose of 50 mg/m² on days 3, 4, and 5) every 3 weeks. No prophylactic granulocyte colony-stimulating factors were used. Results: From September 1998 to April 2000, 56 patients with limited- or extensive-stage SCLC were enrolled and received a total of 235 cycles. Two different etoposide doses were tested in eight patients. At the second level (75 mg/m²), two out of two patients experienced dose-limiting toxicities (neutropenia and thrombocytopenia) and no further dose-escalation was attempted, thus an etoposide dose of 50 mg/m² was defined as the MTD. In the subsequent phase II evaluation, 48 additional patients were enrolled, for a total of 54 patients treated at the MTD. Grade 3/4 neutropenia and thrombocytopenia occurred in 66.7 and 53.7% of patients, respectively. Non-hematologic toxicity was mild, with grade 3 diarrhea and fatigue as the main side effects. Two patients died of neutropenic sepsis (one at 75 mg/m² and the other at 50 mg/m² etoposide). Ten complete and 29 partial responses were reported, for an overall response rate of 72.2% (95% confidence interval, 56.6-85.0%). The median duration of response and median survival were 8.0 and 10 months, respectively, with a 1-year survival probability of 37.5%. Conclusions: The combination of PEG is feasible and well tolerated as front-line chemotherapy in SCLC. A randomized comparison of this triplet is underway.