Pharmacokinetics and safety of lobaplatin plus etoposide in Chinese men older than 65 years with extensive-stage small cell lung cancer: a phase II clinical trial

Abstract

Purpose: This phase II, multicenter, single arm clinical study was first performed to evaluate the therapeutic efficacy and safety of the regimen—a combination of lobaplatin (LBP) and etoposide (VP-16)—and investigate the pharmacokinetics of LBP in Chinese men older than 65 years with extensive-stage small cell lung cancer (SCLC). Methods: Patients older than 65 were treated with the combination of LBP and VP-16 for 4–6 cycles through intravenous drip. The initial dose of VP-16 was 100 mg/m2/day for d1-d3 in each 21-day cycle, while LBP was administrated for d1 in each cycle based on creatinine clearance (Ccr), 20 mg/m2 for Ccr < 60 mL/min; 25 mg/m2 for 60 ≤ Ccr < 80 mL/min and 30 mg/m2 for Ccr ≥ 80 mL/min. Efficacy, safety and pharmacokinetics were evaluated to confirm the therapeutic effect. Results: Thirteen elderly patients were enrolled and three patients were discontinued. The median progress-free survival was 129 days and the median overall survival was 238 days, which caused a significantly prolonged survival rate of 38.5% and a higher disease control rate of 80%. Most frequent adverse events were mild to moderate containing leukopenia, neutropenia, anemia, nausea and anorexia. Pharmacokinetic analysis revealed that there is no significant difference between LP-D1 and LP-D2 at the same dosage level. With the dosage increasing, the elimination clearance showed a slowing tendency, especially for 30 mg/m2 group. Conclusions: LBP (20, 25, 30 mg/m2) in combination with VP-16 (100 mg/m2) could inhibit the elderly SCLC disease process, prolong their survival time and reduce adverse reactions via preliminary assessment and provide guidance for further investigation.