Combination chemotherapy of vinorelbine and cisplatin: a phase I pharmacokinetic study in patients with metastatic solid tumors.

Background: Vinorelbine (VRL)-cisplatin (CDDP) is an active doublet for advanced non-small cell lung cancer. CDDP has a narrow therapeutic index and may produce a cumulative nephrotoxicity over the treatment period. This study was to assess the risks of drug-drug interaction (DDI) over 3 consecutive cycles of VRL-CDDP combined treatments. Patients and Methods: An open-label, nonrandomised, phase I study, was carried out. Patients with normal hepatic/renal functions. D1: CDDP 100 mg/m(2) - D1, D8: oral VRL 60 mg/m(2) q3w. Pharmacokinetics (PK) over the first 3 cycles. PK comparison between cycles and between study vs. literature. Results: Thirteen patients were evaluable for safety and PK. Adverse events were those frequently observed with CDDP or VRL, and consisted of hematological toxicities, nausea, vomiting and constipation. Concerning VRL and CDDP PK, no difference was detected between the 3 administrations nor between the study, and reference values. Conclusion: The absence of DDI between CDDP and oral VRL was demonstrated over 3 consecutive cycles of therapy.