Phase II study of paclitaxel and valspodar (PSC 833) in refractory ovarian carcinoma: A gynecologic oncology group study
Phase II study of paclitaxel and valspodar (PSC 833) in refractory ovarian carcinoma: A gynecologic oncology group study
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DOI：
10.1200/jco.2001.19.12.2975
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发表时间：
2001-06-15
影响因子：
45.3
通讯作者：
McGuire, WP
中科院分区：
文献类型：
--
作者：
Fracasso, PM;Brady, MF;McGuire, WP
目的：研究紫杉醇联合丙泊酚(PSC 833)治疗晚期上皮性卵巢癌的临床疗效。Valspodar是一种非免疫抑制的环孢素D类似物，可逆转P-糖蛋白介导的多药耐药，与紫杉醇联合应用可能对紫杉醇耐药和难治性卵巢癌有效。患者和方法：患者口服Valspodar 5 mg/kg，qid×12剂，紫杉醇70 mg/m(2)，静脉滴注3h，第2天，即第5或第6剂Valspodar后2小时。这种治疗每21天重复一次。在前三个周期的前三个周期中，在第六次给药前采集一份血样，以评估Valspodar谷的浓度。肿瘤组织行P-糖蛋白免疫组织化学染色。结果：60例入选患者中，58例可评价疗效。有5个部分反应(8.6%；90%可信区间为3.8~20.0；中位反应时间为5.0个月[范围为1.9~10.5个月])。中位无进展生存期为1.5个月(90%CI，1.4~2.4)，观察到3级或4级毒性反应为中性粒细胞减少、贫血、恶心呕吐、周围神经病变和小脑性共济失调，第一周期40例患者中，除2例外，其余患者的药物谷浓度均大于或等于1000 ng/mL。结论：Valspodar联合紫杉醇治疗紫杉醇耐药卵巢癌的疗效有限。紫杉醇和卡铂联合或不联合丙泊达作为晚期卵巢癌一线治疗的国际随机临床试验正在进行中。J Clin Oncol19：2975-2982，(C)2001，美国临床肿瘤学会。
Purpose: A phase II study was conducted to determine the efficacy of paclitaxel and valspodar (PSC 833) in patients with advanced epithelial ovarian cancer. Valspodar, a nonimmunosuppressive cyclosporine D analogue that reverses P-glycoprotein-mediated multidrug resistance, in combination with paclitaxel might be active in paclitaxel-resistant and refractory ovarian cancer.Patients and Methods: Patients received valspodar 5 mg/kg orally qid x 12 doses, paclitaxel (70 mg/m(2) intravenously for 3 hours) was administered on day 2, 2 hours after the fifth or sixth dose of valspodar. This treatment was repeated every 21 days. One blood sample was collected before the sixth dose of valspodar for the first three cycles to evaluate valspodar trough concentration. Tumor tissue was obtained from patients for immunohistochemical staining of P-glycoprotein,Results: Of 60 patients entered, 58 were assessable for response. There were five partial responses (8.6%; 90% confidence interval [CI], 3.8 to 20.0; median duration of response, 5.0 months [range, 1.9 to 10.5 months]). Median progression-free survival was 1.5 months (90% CI, 1.4 to 2.4), Grade 3 or 4 toxicities observed were neutropenia, anemia, nausea and vomiting, peripheral neuropathy, and cerebellar ataxia, The trough concentrations of valspodar were greater than or equal to 1,000 ng/mL in all but two of 40 patients in the first cycle. Immunohistochemical staining for p-glycoprotein was positive for one of two responding patients.Conclusion: Valspodar in combination with paclitaxel has limited activity in patients with paclitaxel-resistant ovarian carcinoma. An international randomized clinical trial of paclitaxel and carboplatin with or without valspodar as first-line therapy in advanced ovarian cancer is underway. J Clin Oncol 19:2975-2982, (C) 2001 by American Society of Clinical Oncology.