PHASE-II TRIAL OF TAXOL, AN ACTIVE-DRUG IN THE TREATMENT OF METASTATIC BREAST-CANCER
PHASE-II TRIAL OF TAXOL, AN ACTIVE-DRUG IN THE TREATMENT OF METASTATIC BREAST-CANCER
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DOI：
10.1093/jnci/83.24.1797-a
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发表时间：
1991-12-18
期刊：
影响因子：
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通讯作者：
HORTOBAGYI, GN
中科院分区：
文献类型：
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作者：
HOLMES, FA;WALTERS, RS;HORTOBAGYI, GN
紫杉醇是一种抗微管药物，已显示出治疗乳腺癌的疗效，但严重的超敏反应导致许多I期临床试验停止。 因此，研究人员和国家癌症研究所建议，这种药物的I期和II期研究使用24小时输注和抗过敏药物。 使用预防超敏反应有效的前驱用药方案，我们已经进行了转移性乳腺癌患者紫杉醇的II期试验。 25例患者给予泰素250 mg/m2，24小时静脉滴注，每21天1次。 这些患者既往仅接受过一种化疗方案，要么是辅助手术，要么是转移性疾病;除2例外，所有患者均接受过阿霉素治疗。 在60%的患者中，疾病的主要部位是内脏。 所有患者均可评估。 1991年4月，在9个月的中位研究时间（范围，5-13+个月），客观缓解率为56%（12%完全和44%部分; 95%置信区间，35%-76%）。 只有8%的患者出现疾病进展。 中位疗程数为11个。 粒细胞减少症是剂量限制性毒性反应，但232个疗程中仅5%发生中性粒细胞减少症伴发热。 大多数患者出现慢性手套和长袜神经病，但未发生过敏反应。 我们的结论是，紫杉醇是一种治疗转移性乳腺癌的活性药物，值得继续研究。 目前，我们正在进行紫杉醇加阿霉素的I期试验。 未来的试验应该解决最佳有效剂量，最佳的组合顺序，肿瘤耐药机制，以及剂量限制性毒性作用（特别是紫杉醇作为单一药物或药物组合的心脏毒性作用）。
Taxol, an antimicrotubule agent, has shown promise for efficacy in treatment of breast cancer, but severe hypersensitivity reactions led to cessation of many phase I clinical trials. Consequently, investigators and the National Cancer Institute recommended that phase I and II studies of this agent use 24-hour infusions and antiallergic medications. Using a premedication regimen effective in preventing hypersensitivity reactions, we have performed a phase II trial of taxol in patients with metastatic breast cancer. Taxol was administered to 25 patients at a dose of 25o mg/m2 by 24-hour infusion every 21 days. These patients had received only one prior chemotherapy regimen, either adjuvant to surgery or for metastatic disease; all but two had received doxorubicin. In 60% of the patients, the dominant site of disease was the viscera. All patients were assessable. In April 1991, at a median time on study of 9 months (range, 5-13+ months), the objective response rate was 56% (12% complete and 44% partial; 95% confidence interval, 35%-76%). Disease progressed in only 8% of the patients. The median number of courses of therapy was 11. Granulocytopenia was the dose-limiting toxic effect, but neutropenia with fever occurred in only 5% of 232 courses. A chronic glove-and-stocking neuropathy developed in most patients, but no allergic reactions occurred. We conclude that taxol is an active agent in the treatment of metastatic breast cancer and that it warrants continued study. Currently, we are conducting a phase I trial of taxol plus doxorubicin. Future trials should address the optimal effective dose, the optimal sequencing of combinations, mechanisms of drug resistance in tumors, and dose-limiting toxic effects (particularly cardiac toxic effects of taxol given as a single agent or in drug combinations).