A pilot phase II trial of all-trans retinoic acid (Vesanoid) and paclitaxel (Taxol) in patients with recurrent or metastatic breast cancer
A pilot phase II trial of all-trans retinoic acid (Vesanoid) and paclitaxel (Taxol) in patients with recurrent or metastatic breast cancer
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DOI：
10.1007/s10637-010-9478-3
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发表时间：
2011-12-01
影响因子：
3.4
通讯作者：
Wieder, Robert
中科院分区：
文献类型：
--
作者：
Bryan, Margarette;Pulte, E. Dianne;Wieder, Robert
目的：我们研究了每周一次紫杉醇和全反式视黄酸 (ATRA) 联合疗法对既往接受过治疗的转移性或复发性乳腺癌患者的耐受性、治疗反应、进展时间和生存期。我们的理由是基于临床前研究，证明紫杉烷类药物的细胞毒性作用增强以及 ATRA 诱导分化。患者和方法：17 名既往接受过治疗的转移性或复发性乳腺癌患者入组接受全反式视黄酸（Vesanoid、维A酸、Hoffman-La Roche, Inc.）45 mg/m(2) PO 治疗方案，每天口服 45 mg/m(2)，持续 4 天，从紫杉醇（Taxol，Bristol-Myers Squibb，Plainsboro，NJ）治疗前 2 天开始（Taxol，Bristol-Myers Squibb，Plainsboro，NJ）80 mg/m(2) 每周静脉注射一次，持续 3 周，以 28 天为一个周期重复，直至疾病进展或不再耐受。对患者的毒性、反应、进展时间和生存进行评估。患者主要是非裔美国人和拉丁裔，他们代表了我们癌症中心服务的人群。结果：该方案的耐受性相对较好。发生 9 起 3 级中毒事件和 1 起 4 级中毒事件。我们实施了 162 个治疗周期，平均每位患者 7.5 个（范围 1-22，中位数 5）。 3 名患者获得部分缓解（17.6%），10 名患者疾病稳定（58.8%），总体临床获益为 76.4%。中位进展时间为 6.0 个月（范围 1-21，平均 7.7 个月）。 14 名可评估患者的中位生存期为 16 个月（范围 1-68 个月，平均 25.2 个月）。结论：数据表明，这是一种耐受性良好的治疗方案，反应率适中，但进展时间和生存率与单独使用紫杉醇的报道相似，并且在该患者样本中疾病稳定率相对较高。
Purpose: We investigated a combination therapy with weekly paclitaxel and all trans-retinoic acid (ATRA) for tolerability, response to treatment, time to progression and survival in previously treated patients with metastatic or recurrent breast cancer. Our rationale was based on preclinical studies demonstrating potentiation of the cytotoxic effects of taxanes and induction of differentiation by ATRA. Patients and methods: Seventeen patients with previously treated metastatic or recurrent breast cancer were enrolled to a regimen of all-trans retinoic acid (Vesanoid, tretinoin, Hoffman-La Roche, Inc.) 45 mg/m(2) PO daily for 4 days starting 2 days before a 1 h treatment with paclitaxel (Taxol, Bristol-Myers Squibb, Plainsboro, NJ) 80 mg/m(2) IV administered weekly for 3 weeks, repeated in 28 day cycles until disease progression or until no longer tolerated. Patients were evaluated for toxicity, response, time to progression and survival. Patients were primarily African American and Latino, representative of the population served by our Cancer Center. Results: The regimen was relatively well tolerated. There were nine grade 3 and one grade 4 toxic events. We administered 162 treatment cycles with a mean of 7.5 per patient (range 1-22, median 5). Three patients had a partial response (17.6%) and ten patients had stable disease (58.8%), with an overall clinical benefit of 76.4%. Median time to progression was 6.0 months (range 1-21, mean 7.7 months). Fourteen evaluable patients had a median survival of 16 months (range 1-68 months, mean 25.2 months). Conclusions: The data suggest this is a well tolerated regimen with modest response rates but with time to progression and survival rates similar to those reported for paclitaxel alone and relatively high rates of stable disease in this sample of patients.