Department of Obstetrics, Gynecology and Reproductive Sciences, Division of Gynecologic Oncology, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, Box 1170, New York, NY, 10029, USA.
J Ovarian Res. 2019 Apr 25;12(1):36. doi: 10.1186/s13048-019-0506-4.
Epithelial ovarian cancer has the highest fatality rate of all gynecologic malignancies. Although the majority of patients achieve complete clinical response after initial cytoreductive surgery and platinum-based chemotherapy, most recur and almost all will eventually acquire platinum-resistance for which treatment options become limited. The objective of the study was to describe response and tolerability of metronomic chemotherapy regimen GFIP/BDC, a modification of the G-FLIP regimen, in patients with persistent or recurrent epithelial ovarian, fallopian tube, and primary peritoneal cancer.
A retrospective descriptive analysis of 20 patients from a single academic institution who received combination GFIP/BDC therapy from January 1, 2011 to August 31, 2016 for persistent or recurrent EOC/FT/PP. Treatment consisted of a 2-day combination of gemcitabine 300 mg, 5-fluorouracil 500 mg/m2, irinotecan 20-30 mg/m2, cisplatin 20 mg/m2, bevacizumab 4 mg/kg, docetaxel 20 mg/m2, and cyclophosphamide 200 mg/m2 administered every 14 days. Toxicities were retrospectively graded using CTCAE v4.0.
Twenty patients were identified with a median age 57.5 years (range 32-71). A total of 85% of patients were non-Hispanic white, 90% had cancer of high-grade serous histology, and all had a GOG performance status of 0-1. Patients had received a median of 3 prior regimens and 95% were platinum-resistant. Median number of cycles of GFIP/BDC administered was 9 (range 3-48) and patients remained on treatment for a median of 5.1 months (range 1.5-24). Eleven patients (55%) experienced a partial clinical response with a median duration of 6 months (range 1.5-20). Six patients (30%) survived progression free for at least 6 months. Ten patients (50%) experienced at least one grade 3/4 adverse event. Grade 3 adverse events were hematologic (n = 5), constitutional (n = 3), gastrointestinal (n = 3), neurologic (n = 2), and vascular (n = 1). There was only one grade 4 adverse event which was severe neutropenia. Patients discontinued treatment due to disease progression 65% (n = 13), toxicity 20% (n = 4), patient preference 10% (n = 2), and 5% (n = 1) is currently on treatment.
Selected patients with epithelial ovarian, fallopian tube or primary peritoneal cancer who have failed multiple lines of conventional cytotoxic treatment may benefit from GFIP/BDC. Toxicity might be a limiting factor for administration.
上皮性卵巢癌是所有妇科恶性肿瘤中死亡率最高的。尽管大多数患者在初始减瘤手术后和铂类为基础的化疗后达到完全临床缓解,但大多数患者会复发,几乎所有患者最终都会获得铂类耐药,从而治疗选择受限。本研究的目的是描述改良的 G-FLIP 方案 GFIP/BDC 方案的节拍化疗方案在持续性或复发性上皮性卵巢癌、输卵管癌和原发性腹膜癌患者中的反应和耐受性。
对 2011 年 1 月 1 日至 2016 年 8 月 31 日期间在一家学术机构接受 GFIP/BDC 联合治疗的持续性或复发性 EOC/FT/PP 的 20 例患者进行回顾性描述性分析。治疗方案为吉西他滨 300mg、5-氟尿嘧啶 500mg/m2、伊立替康 20-30mg/m2、顺铂 20mg/m2、贝伐单抗 4mg/kg、多西他赛 20mg/m2 和环磷酰胺 200mg/m2,每 14 天给药 2 天。采用 CTCAE v4.0 对毒性进行回顾性分级。
共确定了 20 例患者,中位年龄为 57.5 岁(范围 32-71 岁)。85%的患者为非西班牙裔白人,90%的患者为高级别浆液性组织学肿瘤,所有患者的 GOG 表现状态均为 0-1。患者接受了中位数为 3 个疗程的治疗,95%的患者对铂类耐药。GFIP/BDC 治疗的中位数周期数为 9(范围 3-48),患者的中位治疗时间为 5.1 个月(范围 1.5-24)。11 名患者(55%)出现部分临床缓解,中位缓解持续时间为 6 个月(范围 1.5-20)。6 名患者(30%)至少无进展生存期为 6 个月。10 名患者(50%)至少出现 1 次 3/4 级不良事件。3 级不良事件为血液学(n=5)、一般情况(n=3)、胃肠道(n=3)、神经(n=2)和血管(n=1)。只有 1 例 4 级不良事件为严重中性粒细胞减少症。因疾病进展(65%,n=13)、毒性(20%,n=4)、患者意愿(10%,n=2)和 5%(n=1)停止治疗。
接受过多线常规细胞毒性治疗后失败的上皮性卵巢癌、输卵管癌或原发性腹膜癌患者可能从 GFIP/BDC 中获益。毒性可能是给药的一个限制因素。