Is cisplatin required for the treatment of non-small-cell lung cancer? Experience and preliminary results of a phase I/II trial with topotecan and vinorelbine

Platinum-based chemotherapy is considered standard treatment for advanced n on-small-cell lung cancer (NSCLC). However, toxicity of most platinum-based regimens is substantial and requires close monitoring and supportive care. Over the past decade, paclitaxel, docetaxel, vinorelbine, gemcitabine, iri notecan, and topotecan have been introduced into the clinic. These newer ag ents have shown promising activity against NSCLC with a favorable toxicity profile as single agents. For patients with metastatic NSCLC, palliation is the main goal of therapy. Therefore, treatment should be easy to administe r on an outpatient basis. We explored a novel combination therapy avoiding platinum. Patients with recurrent or metastatic NSCLC were treated with int ravenous (i.v.) topotecan (0.5-1.0 mg/m(2)/day x 5) and i.v. vinorelbine (2 0-30 mg/m(2)/day on day 1 and day 5) in 21-day cycles. Dose-limiting toxici ty (DLT) was defined separately with or without the addition of granulocyte colony-stimulating factor (G-CSF) support. Twenty-nine patients have been enrolled to date. At i.v. topotecan doses of 0.75-1.0 mg/m(2)/day and i.v. vinorelbine of 25 mg/m(2)/day, neutropenia was frequent but of short durati on (<7 days). The DLT of i.v. topotecan (0.85 mg/m(2)) in the absence of G- CSF support was based on myelosuppression with neutropenic fever. With the addition of G-CSF, a DLT has not been reached. Nonhematologic toxicities in cluded mild to moderate fatigue and constipation. An overall clinical respo nse rate of 42% was achieved, with responses noted at all dose levels. At a short median follow-up of 15 months, the median survival for all patients is 13 months. In conclusion, the combination regimen of topotecan and vinor elbine is feasible for outpatient administration and is well tolerated with less toxicity than platinum-based regimens. Preliminary response data demo nstrate good tumor activity, suggesting that this regimen could make an exc ellent palliative treatment for advanced NSCLC. Copyright (C) 2001 S. Karge r AG, Basel.