甲磺酸伊马替尼治疗铂类和紫杉烷类耐药复发性低级别浆液性卵巢癌、腹膜或输卵管癌的 II 期临床试验。

Phase II trial of imatinib mesylate in patients with recurrent platinum- and taxane-resistant low-grade serous carcinoma of the ovary, peritoneum, or fallopian tube.

机构信息

Department of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77230-1439, USA.

出版信息

Gynecol Oncol. 2012 Jun;125(3):640-5. doi: 10.1016/j.ygyno.2012.02.034. Epub 2012 Feb 28.

DOI:10.1016/j.ygyno.2012.02.034

PMID:22387451

Abstract

OBJECTIVE

To evaluate the efficacy and tolerability of imatinib mesylate in patients with recurrent low-grade serous carcinoma (LGSC) of the ovary, peritoneum, or fallopian tube.

METHODS

This open-label, single-institution phase II trial enrolled patients with platinum-resistant LGSC who had measurable disease, had received up to 4 platinum- and/or taxane-containing chemotherapy regimens, and had been previously screened for at least one imatinib targeted biomarker (c-kit, platelet-derived growth factor receptor [PDGFR]-β, or bcr-abl). Imatinib (600 mg) was administered daily for one 6-week course and continued in the absence of toxicity and disease progression.

RESULTS

Thirteen patients were enrolled; 12 were evaluable for toxicity, and 11 were evaluable for response. A total of 17 courses were administered (median, 1 course; range, 1-5 courses). Complete or partial responses were not observed. One patient had stable disease for 7.3 months. c-Kit, bcr-abl, or PDGFR-β were present in 48%, 77%, and 100% of patients, respectively. No correlation between best response (stable disease) and the presence of imatinib-targeted biomarkers was observed. Adverse events included grade 3 skin rash in one patient leading to discontinuation of the drug, and grade 3 febrile neutropenia and grade 2 weight gain in two patients leading to dose reductions. The most common grade 1 or 2 toxicities were fatigue (66%), nausea/vomiting (66%), and diarrhea (41%); grade 3 toxicities included skin rash and granulocytopenia events. No grade 4 or 5 toxicities were observed. The median progression-free survival time was 1.3 months (95% CI, 1.27, 1.40 months), and the median overall survival time was 14.9 months (95% CI, 11.0, 18.9 months).

CONCLUSION

Imatinib is well-tolerated but has no activity in patients with platinum- and taxane-resistant LGSC or the ovary, peritoneum, or fallopian tube.

摘要

目的

评估甲磺酸伊马替尼治疗复发性低级别浆液性卵巢癌、腹膜或输卵管癌患者的疗效和耐受性。

方法

这是一项开放标签、单中心的 2 期临床试验，招募了铂类耐药的低级别浆液性卵巢癌、腹膜或输卵管癌患者，这些患者有可测量的疾病，接受过最多 4 个含铂类和/或紫杉烷类的化疗方案，并且之前至少筛选过一种伊马替尼靶向生物标志物（c-kit、血小板衍生生长因子受体-β或 bcr-abl）。每天给予甲磺酸伊马替尼 600mg，每 6 周为一个疗程，在无毒性和疾病进展的情况下继续使用。

结果

共纳入 13 例患者，12 例可评估毒性，11 例可评估疗效。共给予 17 个疗程（中位数为 1 个疗程；范围为 1-5 个疗程）。未观察到完全或部分缓解。1 例患者疾病稳定持续 7.3 个月。c-kit、bcr-abl 或 PDGFR-β 在分别有 48%、77%和 100%的患者中存在。最佳反应（疾病稳定）与伊马替尼靶向生物标志物的存在之间未观察到相关性。不良事件包括 1 例患者出现 3 级皮疹导致药物停药，2 例患者出现 3 级发热性中性粒细胞减少症和 2 级体重增加导致剂量减少。最常见的 1 级或 2 级毒性为乏力（66%）、恶心/呕吐（66%）和腹泻（41%）；3 级毒性包括皮疹和粒细胞减少症。未观察到 4 级或 5 级毒性。中位无进展生存期为 1.3 个月（95%CI，1.27-1.40 个月），中位总生存期为 14.9 个月（95%CI，11.0-18.9 个月）。