Phase I study of Doxil and vinorelbine in metastatic breast cancer
Phase I study of Doxil and vinorelbine in metastatic breast cancer
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DOI：
10.1023/a:1008323200102
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发表时间：
1999-09-01
影响因子：
50.5
通讯作者：
Winer, EP
中科院分区：
文献类型：
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作者：
Burstein, HJ;Ramirez, MJ;Winer, EP
背景：长春瑞滨和 Doxil（脂质体阿霉素）是转移性乳腺癌的活性化疗药物。一项 I 期研究旨在评估联合疗法。 患者和方法： 招募了 30 名患有转移性乳腺癌的女性。剂量限制毒性是通过剂量递增方案确定的，并仅针对第一个治疗周期进行定义。在第一个治疗周期期间进行了药代动力学研究。结果：在第 1 天服用 Doxil 30 mg/m(2) 和第 1 天和第 8 天服用长春瑞滨 25 mg/m(2) 的第一组患者中，患者出现严重中性粒细胞减少症。此后，长春瑞滨给药改为每个周期的第 1 天和第 15 天。在 Doxil 50 mg/m(2) 和长春瑞滨 25 mg/m(2) 时观察到剂量限制毒性。 Doxil 40 mg/m(2) 和长春瑞滨 30 mg/m(2) 被定义为最大耐受剂量。在此剂量水平下几乎没有发现毒性（主要是中性粒细胞减少症），并且没有明显的恶心、呕吐或脱发。尽管 63% 的患者之前接受过蒽环类化疗，但只有 1 名患者出现 2 级心脏毒性。药代动力学研究显示，在给予 Doxil 后数天内，患者会长时间暴露于高浓度的阿霉素。结论：Doxil 和长春瑞滨的联合化疗可为患有转移性乳腺癌的女性提供两种活性药物的治疗，并且似乎具有良好的毒性特征。对于 II 期研究，建议每 28 天给药一次，第 1 天服用 Doxil 40 mg/m(2)，第 1 天和第 15 天服用长春瑞滨 30 mg/m(2)。
Background: Vinorelbine and Doxil (liposomal doxorubicin) are active chemotherapeutic agents in metastatic breast cancer. A phase I study was designed to evaluate combination therapy.Patients and methods: Thirty women with metastatic breast cancer were enrolled. Dose-limiting toxicity was determined through a dose escalation scheme, and defined for the first treatment cycle, only. Pharmacokinetic studies were performed during the first cycle of treatment.Results: In the first cohort of Doxil 30 mg/m(2) day 1 and vinorelbine 25 mg/m(2) days 1 and 8, patients experienced severe neutropenia. Vinorelbine administration was changed thereafter to days 1 and 15 of each cycle. Dose limiting toxicity was observed at Doxil 50 mg/m(2) and vinorelbine 25 mg/m(2). Doxil 40 mg/m(2) and vinorelbine 30 mg/m(2) was defined as the maximally tolerated dose. Few toxicities (principally neutropenia) were seen at this dose level, with the notable absence of significant nausea, vomiting, or alopecia. Though 63% of patients had received prior anthracycline-based chemotherapy, only one patient developed grade 2 cardiac toxicity. Pharmacokinetic studies revealed prolonged exposure to high doxorubicin concentrations for several days following Doxil administration.Conclusions: Combination chemotherapy with Doxil and vinorelbine affords treatment with two active drugs in women with metastatic breast cancer, and appears to have a favorable toxicity profile. A schedule of Doxil 40 mg/m(2) day 1 and vinorelbine 30 mg/m(2) days 1 and 15 given every 28 days is recommended for phase II studies.