Cisplatin-paclitaxel weekly schedule in advanced solid tumors: A phase I study

Purpose: The objective of our study was to determine the maximumtolerable doses (MTDs) of both paclitaxel and cisplatin when given in a weeklyschedule alone or simultaneously with G-CSF in advanced solid neoplasms.Patients and methods: Patients with advanced cancer eitherchemotherapy-naïve or resistant to standard treatments receivedpaclitaxel in a three-hour infusion followed by cisplatin, with or without theaddition of r-HuG-CSF (5 µg/kg s.c. days three to five). The startingdoses of CDDP and paclitaxel were 25 mg/m²/week and 45mg/m²/week, respectively. During the first six courses thedosages of the two drugs were alternately escalated by 20% (CDDP = 5mg/m²/week, and paclitaxel 10 mg/m²/week) ateach step until the appearance of dose-limiting toxicity (DLT) in one-thirdor more of the patients enrolled in that cohort.Results: Fifty-five patients with cancer (16 lung, 16 breast, 11ovarian, 7 head and neck, 1 renal, 1 esophageal, 1 cervical, 1 soft-tissuesarcoma, and 1 of unknown primary), 25 of whom were pretreated, were enteredinto the study. A total of 439 weekly courses were delivered. Inchemotherapy-naïve patients, the MTDs of cisplatin and paclitaxel were30 mg/m²/week and 65 mg/m²/week, respectively,in the absence of G-CSF support, which increased to 40mg/m²/week and 85 mg/m²/week, respectively,when G-CSF was given. There were no toxic deaths in this study. Neutropeniawas the main dose-limiting toxicity (100/439 courses), but was seldom severe.Neurotoxicity was quite frequent (18 of 55 patients for the total of 88courses) but never dose-limiting. It was more frequent and clinically relevantin cisplatin-pretreated patients. Overall 18 patients (eight ovarian, fivebreast, three lung, and two head and neck) achieved objective responses.Conclusions: The cisplatin–paclitaxel weekly administrationseems a safe, practical and effective therapeutical approach in patients withadvanced solid neoplasms. Large phase II trials are warranted to accuratelydefine the efficacy of this schedule in cisplatin-paclitaxel sensitive tumors.