ABSTRACT
PURPOSE: CPT-11 (60 mg/m2 on days 1, 8 and 15) in combination with CDDP (80 mg/m2 on day 1) has shown promising antitumor activity for non-small-cell lung cancer (NSCLC), but dose-limiting toxicities (DLT) are leukopenia and diarrhea, with a wide variation among patients. To estimate weekly CDDP administration in combination with CPT-11, a phase I study for patients with advanced NSCLC was conducted. METHODS: Patients were treated with CPT-11 at a fixed dose of 60 mg/m2 together with CDDP at 27 mg/m2 (level 1, 6 patients), 33 mg/m2 (level 2, 12 patients), and 40 mg/m2 (level 3, 6 patients) with 1600 ml hydration on days 1, 8 and 15 over 4 weeks. During the treatment course, drug was not administered on the day it was due in the presence of leukopenia (< 3000/ml) and/or diarrhea. RESULTS: The planned administration was completed in 5 of 6 patients at level 1, 6 of 12 patients at level 2, and 2 of 6 patients at level 3. The most common toxicity observed was leukopenia (five patients with grade 3 and one patient with grade 4). Leukopenia was considered to be a DLT, and the maximum tolerated dose (MTD) was level 2. Although there were patients who suffered from diarrhea (four patients with higher than grade 2), diarrhea was judged not to be a DLT with this weekly regimen. Nausea and vomiting were mild. Pharmacokinetic analysis of free platinum from CDDP demonstrated that the area under the curve (AUC) from 33 mg/m2 CDDP was 0.92 +/- 0.29 microg/ml h. In 13 patients evaluated for response, the response rate was 54%. CONCLUSION: The value of weekly administration of CDDP in combination with CPT-11 was shown by (1) diarrhea not being dose-limiting, (2) mild nausea, (3) well-maintained AUC of free platinum, and (4) promising activity.
