CLINICAL-PHASE-I STUDY WITH ONE-HOUR PACLITAXEL INFUSION

Background. Paclitaxel (PAC) is one of the major anti-cancer drugs, ef fective in different tumors. Studies with 24-hour infusion with 135 mg /m(2) and a three-hour infusion with 175 mg/m(2) showed a significant schedule-dependent toxicity. We evaluated a one-hour infusion schedule within a phase I study to determine the dose limiting toxicity (DLT), the maximum tolerated dose (MTD), and the anti-cancer efficacy. Patie nts and methods: Patients with advanced malignant tumors were treated within cohorts by one-hour infusional paclitaxel starting with 150 mg/ m(2) and stepwise escalation with 25 mg/m(2) increments. Therapy was r epeated in three-week intervals. Cycles were repeated until progressio n. Toxicity was closely monitored, anti-cancer efficacy was only evalu ated in those patients who received at minimum two treatment cycles. R esults: Thirty-four patients entered the study(ll NSCLC, five SCLC, se ven ovarian cancer, one cervix cancer, nine MBC, one HN cancer). The M TD was PAC 250 mg/m(2). The DLT was central and peripheral neuropathy (WHO grade 3). Other significant toxicities were fatigue, myalgia/arth ralgia and paraesthesia. No significant myelotoxicity was observed. To tally twentyone patients were evaluable for response. A partial respon se was observed in five (24%) patients (two NSCLC, two ovarian cancer, one head and neck cancer). Three (14%) patients had stable disease an d in 13 (62%) patients progressive disease was observed. Conclusions. Paclitaxel 225 mg/m(2) on day 1 administered as one-hour infusion and repeated every three weeks can be given safely, featured no relevant m yelotoxicity, and is the recommended dose for phase II studies.