Single-agent use of Taxol (paclitaxel) in breast cancer.
The search for new active agents and strategies to improve the prognosis for patients with stage IV breast cancer has led to examination of paclitaxel. Several clinical trials have been undertaken to determine its optimal use and clarify its role in the treatment of breast cancer and other malignancies. Several phase II trials involving breast cancer patients with limited prior therapy have yielded overall response rates (complete response and partial response) of 44% to 62% among women receiving paclitaxel. Treatment was generally well tolerated, with febrile neutropenia the most common side effect. An interim analysis of the European-Canadian Randomized Trial in Metastatic Breast Cancer demonstrated safety and efficacy of paclitaxel in a multicenter setting. Among the 234 patients evaluable for response, 29% (34/117) responded at 175 mg/m2 paclitaxel and 22% responded (26/117) at 135 mg/m2. Treatment was well tolerated at both dose levels; responses continue to evolve in patients who remain on study. Among patients with extensive prior therapy (> 2 prior regimens for stage IV disease), paclitaxel also has demonstrated safety and efficacy. At Memorial Sloan-Kettering Cancer Center, responses were noted among 36% of patients who had received two prior treatments and 21% of those who had received 3 or more. Paclitaxel was administered at 200 mg/m2 plus G-CSF. Other studies involving heavily pretreated patients yielded overall response rates as high as 53%. The concerns about cross-resistance between paclitaxel and doxorubicin (or other agents for which resistance is thought to be at least partly due to P-glycoprotein-mediated pleiotropic drug resistance) also are addressed.
Seidman
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AD
Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, New York.
D000903:Antibiotics, Antineoplastic / Q000494:pharmacology; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D017322:Clinical Trials, Phase II as Topic; D017326:Clinical Trials, Phase III as Topic; D004334:Drug Administration Schedule; D004351:Drug Resistance; D005260:Female; D006801:Humans; D009367:Neoplasm Staging; D017239:Paclitaxel / Q000494:pharmacology / Q000627:therapeutic use*; D016879:Salvage Therapy
D000903:Antibiotics, Antineoplastic; D017239:Paclitaxel