968 Cisplatin-paclitaxel weekly administration. A dose-finding study

To determine the MTDs of both paclitaxel and cisplatin when given in a weekly schedule, we have conducted this phase I study. To date, 15 patients with different neoplasms (6 lung, 4 ovarian, 5 others) have been treated, for a total of 93 courses. The starting doses of cisplatin and paclitaxel were 25 mg/m 2 /week and 45 mg/m 2 /week respectively. Dosage of the two drugs was alternately escalated by 5 mg for CDDP and 10 mg for paclitaxel until dose limiting toxicity occurred in one third or more patients of each cohort during the first 6 courses. At the 4th escalation (CDDP = 30 mg/m 2 /week and paclitaxel 65 mg/m 2 /week) 2/6 patients experienced DLT (in both cases it was neutropenia). Neurotoxicity was very frequent. It occurred in 7/15 patients and in 3 was of grade 2 WHO. Four patients complained of painful, although reversible, cramps. Mucositis and diarrhea were also frequent but mild. They occurred in 10 and 7 patients, respectively (only one patient had grade 3 for diarrhea). In conclusion, neutropenia seems to be the DLT when CDDP and paclitaxel are administered together in a weekly schedule. The MTDs are CDDP = 30 mg/m 2 and paclitaxel = 55 mg/m 2 in absence of hematopoietic growth factors. A further evaluation of the level 4 (CDDP = 30 mg/m 2 and paclitaxel = 65 mg/m 2 ) using G-CSF is ongoing.