phase I study
Springer Online Journal Archives 1860-2000
Abstract Background: Paclitaxel (PAC) is one of the major anti-cancer drugs,effective in different tumors. Studies with 24-hour infusion with 135mg/m2 and a three-hour infusion with 175 mg/m2showed a significant schedule-dependent toxicity. We evaluated a one-hourinfusion schedule within a phase I study to determine the dose limitingtoxicity (DLT), the maximum tolerated dose (MTD), and the anti-cancerefficacy. Patients and methods: Patients with advanced malignant tumors weretreated within cohorts by one-hour infusional paclitaxel starting with 150mg/m2 and stepwise escalation with 25 mg/m2increments. Therapy was repeated in three-week intervals. Cycles wererepeated until progression. Toxicity was closely monitored, anti-cancerefficacy was only evaluated in those patients who received at minimum twotreatment cycles. Results: Thirty-four patients entered the study (11 NSCLC, five SCLC,seven ovarian cancer, one cervix cancer, nine MBC, one HN cancer). The MTDwas PAC 250 mg/m2. The DLT was central and peripheralneuropathy (WHO grade 3). Other significant toxicities were fatigue,myalgia/arthralgia and paraesthesia. No significant myelotoxicity wasobserved. Totally twentyone patients were evaluable for response. A partialresponse was observed in five (24%) patients (two NSCLC, two ovariancancer, one head and neck cancer). Three (14%) patients had stabledisease and in 13 (62%) patients progressive disease was observed. Conclusions: Paclitaxel 225 mg/m2 on day 1 administered asone-hour infusion and repeated every three weeks can be given safely, featuredno relevant myelotoxicity, and is the recommended dose for phase II studies.
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