Phase I-II Trial of Gemcitabine-Based First-Line Chemotherapies for Small Cell Lung Cancer in Elderly Patients with Performance Status 0-2 The G-Step Trial

Introduction Treatment of elderly patients with small cell lung cancer (SCLC) is based on scanty evidence. Methods Patients with extensive SCLC, age >70 years, and performance status 0–2 were eligible for a study looking for optimal two-drug combination of gemcitabine (Gem) with vinorelbine (Vin), etoposide (Eto), cisplatin (Cis), or carboplatin (Car). Gemcitabine dose was the same (1000 mg/m 2 , days 1–8) in all combinations. A two-stage minimax flexible design for response was applied to GemVin combination (Vin 25 mg/m 2 , days 1–8). For GemCar, GemCis, GemEto, a phase I-II Bayesian design was applied, looking for the optimal dose of the partner drugs. Objective response rate ≥60% and unacceptable toxicity ≤25% were required to define a combination worthy of further studies. Results Median age of 78 eligible patients was 74 years. GemVin produced a 36.7% objective response rate. GemEto and GemCis arms were found not sufficiently active. GemCar produced 16 responses (14 with area under the curve [AUC] 3.5 and 2 with AUC 4.0) in 26 patients (61.5%) and 6 cases of unacceptable toxicity (3 at each Car dose). Conclusions In elderly patients with extensive SCLC, GemVin, GemEto, and GemCis are not enough active and do not merit further studies. Gem plus Car might deserve further attention.