CISPLATIN-PACLITAXEL WEEKLY SCHEDULE IN ADVANCED SOLID TUMORS - A PHASE-I STUDY

Purpose: The objective of our study was to determine the maximum toler able doses (MTDs) of both paclitaxel and cisplatin when given in a wee kly schedule alone or simultaneously with G-CSF in advanced solid neop lasms. Patients and methods: Patients with advanced cancer either chem otherapy-naive or resistant to standard treatments received paclitaxel in a three-hour infusion followed by cisplatin, with or without the a ddition of r-HuG-CSF (5 mu g/kg s.c. days three to five). The starting doses of CDDP and paclitaxel were 25 mg/m(2)/week and 45 mg/m(2)/week , respectively. During the first six courses the dosages of the two dr ugs were alternately escalated by 20% (CDDP = 5 mg/m(2)/week, and pacl itaxel 10 mg/m(2)/week) at each step until the appearance of dose-limi ting toxicity (DLT) in one-third or more of the patients enrolled in t hat cohort. Results. Fifty-five patients with cancer (16 lung, 16 brea st, 11 ovarian, 7 head and neck, 1 renal, 1 esophageal, 1 cervical, 1 soft-tissue sarcoma, and 1 of unknown primary), 25 of whom were pretre ated, were entered into the study. A total of 439 weekly courses were delivered. In chemotherapy-naive patients, the MTDs of cisplatin and p aclitaxel were 30 mg/m(2)/week and 65 mg/m(2)/week, respectively, in t he absence of G-CSF support, which increased to 40 mg/m(2)/week and 85 mg/m(2)/week, respectively, when G-CSF was given. There were no toxic deaths in this study. Neutropenia was the main dose-limiting toxicity (100/439 courses), but was seldom severe. Neurotoxicity was quite fre quent (18 of 55 patients for the total of 88 courses) but never dose-l imiting. It was more frequent and clinically relevant in cisplatin-pre treated patients. Overall 18 patients (eight ovarian, five breast, thr ee lung, and two head and neck) achieved objective responses. Conclusi ons: The cisplatin-paclitaxel weekly administration seems a safe, prac tical and effective therapeutical approach in patients with advanced s olid neoplasms. Large phase II trials are warranted to accurately defi ne the efficacy of this schedule in cisplatin-paclitaxel sensitive tum ors.