A phase I study combining a fixed dose of gemcitabine with differing doses of CPT-11 every two weeks for previously treated non-small cell lung cancer (NSCLC) patients.
Patients and methods: A total of 21 patients with previously treated non-small cell lung cancer were treated every two weeks with CPT-11 followed by gemcitabine. The gemcitabine dose was fixed at 1000 mg/m2. The starting dose of CPT-11 (50 mg/m2) was then escalated different patients in 25 mg/m2 increments until 150 mg/m2 (level 5), the recommended dose as a single agent in Japan.
Results: Dose-limiting toxicity was only observed at level 5, in three of nine patients receiving the highest dose of CPT-11. One patient had grade 3 diarrhea, and two could not continue chemotherapy with grade 1 diarrhea or grade 1 neutropenia on day 15. Hematologic toxicity with this combination regimen, however, was generally mild. No grade 4 neutropenia, and only one case of grade 3 leukopenia was noted at level 5. Compliance with the combination regimen was good and there was no cumulative toxicity with the subsequent courses. Twenty-five courses of therapy were given at level 5 and the percentage of actual delivered doses/planned doses was 82%.
Conclusions: The combination chemotherapy has only very mild toxicity and dose which can be recommended with this regimen are 1000 mg/m2 for gemcitabine and 150 mg/m2 for CPT-11 every two weeks.