PHASE-II TRIAL OF PACLITAXEL AND TOPOTECAN WITH GRANULOCYTE-COLONY-STIMULATING FACTOR SUPPORT IN STAGE-IV BREAST-CANCER

Purpose: This multicenter phase II trial investigated the efficacy and safety of a combination of paclitaxel and topatecan in patients with pretreated metastatic breast cancer. Plasma levels of paclitaxel and t opotecan were obtained during cycle 1 to correlate pharmacokinetic par ameters with toxicity. Patients and Methods: Paclitaxel was administer ed intravenously (IV) at 230 mg/m(2) over 3 hours on day 1 followed by topotecan 1.0 mg/m(2) IV over 30 minutes on days 1 to 5, Patients rec eived an abbreviated premedication regimen that consisted of ranitidin e 50 mg, diphenhydramine 50 mg, and a single 20-mg dose of dexamethaso ne, all administered IV 30 minutes before paclitaxel. Granulocyte colo ny-stimulating factor (G-CSF) was administered at 5 mu g/kg/d subcutan eously starting on day 6 and continuing until the absolute granulocyte count (AGC) was greater than 10,000/mu L. Plasma paclitaxel and topot ecan concentrations were assessed during the first cycle using limited -sampling strategies. Results: Seventeen patients were treated. The ma jority had visceral metastases. Four patients experienced neutropenic fever and one had mild bronchospasm. Only one partial response (PR) wa s observed. Nadir AGC correlated strongly with both duration of paclit axel levels greater than 0.05 mu mol/L and maximum concentration (C-ma x) of paclitaxel. Conclusion: This regimen does not produce a response rate superior to that expected with single agent paclitaxel at doses that do not require growth factor support.