A dose-finding and pharmacokinetic study of nedaplatin in elderly patients with advanced non-small cell lung cancer

Nedaplatin is a second-generation platinum showing favorable activity against non-small cell lung cancer (NSCLC). Dose-limiting toxicity (DLT) is thrombocytopenia, predicted by creatinine clearance (Ccr). This study was conducted to determine the recommended dose, and evaluate the toxicities, pharmacokinetics and efficacy for elderly NSCLC patients.

Patients > or =70 years were stratified into two groups based on renal functions: Group A, Ccr > or = 60 and Group B, 40 < or = Ccr < 60. The initial doses were 80 and 60 mg/m(2) in Groups A and B, respectively. The doses were escalated in 20-mg/m(2) increments to 100 mg/m(2) until DLT.

Chemotherapy-naïve 39 elderly patients (Group A/Group B: 22/17) received a total of 83 cycles. Major toxicities were hematological. In Group A, one of the 15 patients at 100 mg/m(2) experienced DLT (neutropenia) and the recommended dose was determined at 100 mg/m(2). In Group B, three of the five patients had DLTs (leukopenia, neutropenia, thrombocytopenia and febrile neutropenia) at 100 mg/m(2), and the recommended dose was determined at 80 mg/m(2). The percentage decreases of neutrophil were well correlated with total and free-Pt AUCs. Partial responses were observed in 13 (33%) of the 39 patients, and 12 of the 13 patients who responded had a squamous cell carcinoma.

Nedaplatin was administered simply and feasibly by stratifying renal function and exerted favorable antitumor activity for elderly patients with NSCLC, especially on squamous cell carcinoma.