Phase II study of liposomal doxorubicin in refractory ovarian cancer: Antitumor activity and toxicity modification by liposomal encapsulation
Phase II study of liposomal doxorubicin in refractory ovarian cancer: Antitumor activity and toxicity modification by liposomal encapsulation
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DOI：
10.1200/jco.1997.15.3.987
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发表时间：
1997-03-01
影响因子：
45.3
通讯作者：
Liang, LJ
中科院分区：
文献类型：
--
作者：
Muggia, FM;Hainsworth, JD;Liang, LJ
目的：对基于铂类和紫杉醇的治疗方案无效的卵巢癌患者进行了脂质体阿霉素的 II 期研究。选择脂质体阿霉素是因为其相对于游离阿霉素具有更优异的抗卵巢癌异种移植活性，并且在 I 期研究中注意到对难治性卵巢癌患者的活性。 患者和方法：两个机构连续招募了 35 名患者（其中一个机构 22 名，另一个机构 13 名）。所有患者在接受顺铂或卡铂加紫杉醇，或至少一种铂类治疗方案和一种紫杉醇治疗方案后出现疾病进展。患者每 3 周接受静脉 (IV) 脂质体多柔比星 50 mg/m(2) 治疗，如果出现 3 或 4 级毒性，则将剂量减少至 40 mg/m(2)，或者如果 1 或 2 级毒性持续超过 3 周，则将间隔时间延长至 4 周（有时延长至 5 周）。 结果： 9 项临床缓解（1 项完全缓解 [CR]，8 项部分缓解） [PR]) 在 35 名患者 (25.7%) 中观察到，其中 7 名已通过两次连续计算机断层扫描 (CT) 测量得到证实。中位无进展生存期为 5.7 个月，总生存期为 1.5 至 24 个月以上（中位生存期 11 个月）。尽管 13 名患者出现了 3 级或 4 级非血液学皮肤和粘膜毒性（手足综合征或口腔炎），但经过剂量调整后，治疗的耐受性非常好。没有发生明显由药物引起的恶心、脱发、外渗坏死或选举分数降低。结论：脂质体阿霉素对铂类和紫杉醇难治的卵巢癌具有显着的活性。使用脂质体阿霉素实现的反应是持久的并且以最小的毒性维持。这种脂质体制剂应与其他药物联合用于难治性较弱的患者进行进一步评估。 (C) 1997 年，美国临床肿瘤学会。
Purpose: A phase II study of liposomal doxorubicin was conducted in patients with ovarian cancer who failed to respond to platinum- and paclitaxel-based regimens. Liposomal doxorubicin was selected as a result of its superior activity against ovarian cancer xenografts relative to free doxorubicin and activity in refractory ovarian cancer patients that was noted during the phase I study.Patients and Methods: Thirty-five consecutive patients were accrued in two institutions (22 in one and 13 in the other). AII had progressive disease after either cisplatin or carboplatin and paclitaxel, or at least one platinum-based and one paclitaxel-based regimen. Patients received intravenous (IV) liposomal doxorubicin 50 mg/m(2) every 3 weeks with a dose reduction to 40 mg/m(2) in the event of grade 3 or 4 toxicities, or a lengthening of the interval to 4 weeks (and occasionally to 5 weeks) with persistence of grade 1 or 2 toxicities beyond 3 weeks.Results: Nine clinical responses (one complete response [CR], eight partial responses [PRs]) were observed in 35 patients (25.7%), with seven of these having been confirmed by two consecutive computed tomographic (CT) measurements. The median progression-free survival was 5.7 months with an overall survival of 1.5 to 24+ months (median, 11 months). Although 13 patients experienced grade 3 or 4 nonhematologic skin and mucosal toxicities (either hand-foot syndrome or stomatitis), with dose modifications, the treatment was very well tolerated. Nausea that was clearly attributable to the drug, hair loss, extravasation necrosis, or decreases in election fraction did not occur.Conclusion: Liposomal doxorubicin has substantial activity against ovarian cancer refractory to platinum and paclitaxel. The responses achieved with liposomal doxorubicin were durable and maintained with minimal toxicity. This liposomal formulation should be evaluated further in combination with other drugs in less refractory patients. (C) 1997 by American Society of Clinical Oncology.