Weekly administration of topotecan and paclitaxel in pretreated advanced cancer patients: a phase I/II study

Purpose. This study was a phase I/II, cohort, dose-escalation trial of topotecan and paclitaxel. Its aim was to determine the dose-limiting toxicity (DLT) of the combination and to define the maximum tolerated dose (MTD), as a recommended dose for phase II, as well as to get preliminary data on the efficacy (activity) of the drug in pretreated patients with ovarian cancer, small-cell lung cancer (SCLC) and non-small-cell lung cancer (NSCLC). Methods. Included in the study were 52 pretreated patients, 19 with ovarian cancer, 20 with SCLC and 13 with NSCLC. The doses of topotecan were escalated from 1.25 to 2 mg/m(2) and of paclitaxel from 60 to 80 mg/m(2). A minimum of four patients were included at each of the six levels of dose escalation. Results. We found that DLT due to grade 3 and 4 myelotoxicity was at levels 5 and 6 at doses of 1.75 and 80 mg/m(2) (level 5) and 2 and 80 mg/m(2) (level 6) for topotecan and paclitaxel, respectively. The MTD and recommended accepted doses are 1.75 mg/m(2) for topotecan and 70 mg/m(2) for paclitaxel. Of the 52 patients, 17 (33%) showed a response: 1 complete response (1.92%) and 16 partial responses (30.77%). Conclusions. Topotecan combined with paclitaxel administered once weekly for three consecutive weeks repeated for every 28 days resulted in well-tolerated toxicity at doses of 1.75 and 70 mg/m(2), respectively, and a response rate of 33% in pretreated cancer patients.