Paclitaxel and carboplatin: A phase I study in advanced non-small cell lung cancer

In the treatment of non-small cell lung cancer paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) has significant activity and carboplatin has single-agent activity comparable with that of cisplatin, with less pronounced nonhematologic toxicity. The optimal doses of paclitaxel and carboplatin in combination have not been determined. We designed a phase I study combining a fixed paclitaxel dose of 175 mg/m², administered either by 3- or 1-hour infusion, with escalating doses of carboplatin given every 4 weeks. The starting carboplatin dose was 175 mg/m², with planned close increases in increments of 25 mg/m². The primary study objective was to find the maximum tolerated dose of the combination. Secondary objectives were to determine the toxicity profile, response rate, and feasibility of a 1-hour paclitaxel infusion with steroid premeditation delivered only I hour before the paclitaxel infusion. Eligibility criteria included age 18 to 75 years, no prior chemotherapy, stage IIIB to IV disease, Eastern Cooperative Oncology Group performance status 0 to 2, no second tumors, measurable or evaluable disease, and informed consent. We achieved a carboplatin dose level of 300 mg/m³ without reaching the maximum tolerated dose. The dose-limiting toxicity was granulocytopenia. However, only one patient had a neutrophil count less than 500/μL during the first cycle. Other toxicities during the first and remaining 73 delivered cycles were mild to moderate. Only one patient had treatment delayed, and no dose reductions were necessary. Of 22 patients entered, 19 were evaluable for response (two were not evaluable and one was too early to evaluate). Six partial responses (31%; 95% confidence interval, 13% to 57%), five (26%) stable diseases, and eight (42%) disease progressions were observed. No additional side effects were observed with the I-hour paclitaxel infusion and single-dose steroid premeditation I hour before chemotherapy. The study will continue until the paclitexel/carboplatin maximum tolerated dose is reached.