Department of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77230-1439, USA.
Gynecol Oncol. 2012 Jun;125(3):640-5. doi: 10.1016/j.ygyno.2012.02.034. Epub 2012 Feb 28.
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.
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.
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).
Imatinib is well-tolerated but has no activity in patients with platinum- and taxane-resistant LGSC or the ovary, peritoneum, or fallopian tube.
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。
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。
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）。
伊马替尼耐受良好，但对铂类和紫杉烷类耐药的卵巢癌、腹膜或输卵管癌患者无效。
