A phase I and pharmacokinetic study of novel taxane BMS-188797 and cisplatin in patients with advanced solid tumours.

This phase I study investigated the maximum tolerated dose and pharmacokinetics of a 3-weekly administration of BMS-188797, a paclitaxel derivate, at three dose levels (DLs) (80, 110 and 150 mg m(-2) DL), combined with cisplatin (standard dose 75 mg m(-2)). In 16 patients with advanced malignancies treated, one patient experienced dose-limiting febrile neutropenia, sepsis and severe colitis at the 150 mg m(-2) DL; at the 110 mg m(-2) DL one episode of dose-limiting grade 3 diarrhoea/nausea occurred. Grade 3/4 haematological toxicities were leucopenia/neutropenia; grade 3 nonhaematological toxicities were neuropathy, nausea, diarrhoea and stomatits. Objective response was seen in four patients, with three complete remissions in ovarian and cervical cancer patients. Pharmacokinetics of BMS-188797 appeared linear through the 110 mg m(-2), but not through the 150 mg m(-2) DL. The mean+/-SD values for clearance, distribution volume at steady state and terminal half-life during cycle 1 were 317+/-60 ml min(-1) m(-2), 258+/-96 l m(-2) and 30.8+/-7.7 h, respectively. The maximum tolerated and recommended phase II dose for BMS-188797 was 110 mg m(-2) (1-h infusion, every 3 weeks) combined with cisplatin 75 mg m(-2).

Primary chemotherapy with doxorubicin and paclitaxel in patients with early breast cancer: final results of a multicenter phase II study.

PURPOSE: To assess the efficacy and safety of primary systemic treatment with doxorubicin and paclitaxel in patients with early breast cancer. PATIENTS AND METHODS: Forty patients with newly diagnosed, histologically confirmed breast cancer (T2, N0-1, M0) received primary chemotherapy with doxorubicin (60 mg/m2) and paclitaxel (200 mg/m2) in 3-week intervals for up to four courses. RESULTS: A total of 151 cycles were administered. The clinical response rate as assessed by sonographic measurement was 70%, and complete remissions of the primary tumor occurred in two patients. Eight patients (20%) had histologically confirmed complete responses. Predominant toxicity was myelosuppression with grade 3/4 neutropenia in 70% of patients. Non-hematological toxicity was generally moderate. Grade 4 non-hematological toxicities were not observed and grade 3 toxicity was reported with alopecia (98%) and stomatitis (10%). CONCLUSIONS: The combination of doxorubicin and paclitaxel is safe and highly active in patients with early breast cancer. The evaluated schedule is suitable for phase III studies.