Matulonis Ursula A, Horowitz Neil S, Campos Susana M, Lee Hang, Lee Julie, Krasner Carolyn N, Berlin Suzanne, Roche Maria R, Duska Linda R, Pereira Lauren, Kendall Deborah, Penson Richard T
Department of Medical Oncology, Dana-Farber Cancer Institute, Massachusetts General Hospital, Boston MA 02115, USA.
J Clin Oncol. 2008 Dec 10;26(35):5761-6. doi: 10.1200/JCO.2008.17.0282. Epub 2008 Nov 10.
More efficacious, less toxic combinations are needed to treat platinum-sensitive recurrent epithelial ovarian cancer (EOC). Pemetrexed is a multitargeted antifolate with manageable toxicity and has been combined with carboplatin to treat other cancers.
This is a phase II study of carboplatin area under the curve 5 with pemetrexed 500 mg/m(2) administered intravenously on day 1 every 21 days for six cycles or for up to eight cycles if clinical benefit occurred. Eligible patients had platinum-sensitive recurrent EOC, peritoneal serous cancer, or fallopian tube cancer. The primary objective was to determine response rate defined by Response Evaluation Criteria in Solid Tumors; other end points included toxicities, progression-free survival (PFS), and overall survival (OS).
Forty-five patients were accrued; 44 patients received treatment. Overall response rate was 51.1%; there were no complete responses (0%), 23 confirmed partial responses (51.1%), two unconfirmed partial responses (4.4%), 14 patients with stable disease (31.1%), and two patients with progressive disease after two cycles (4.4%). Grade 3 and 4 hematologic toxicities included neutropenia (41%), thrombocytopenia (23%), and anemia (9%); there were no episodes of febrile neutropenia. Grade 3 and 4 nonhematologic toxicities included fatigue (11%), nausea (5%), vomiting (5%), diarrhea (5%), syncope (5%), and pulmonary embolism (5%). Median PFS time was 7.57 months (95% CI, 6.44 to 10.18 months), mean OS time was 20.3 months, and median OS has not yet been reached with a mean follow-up time of 15.3 months.
Carboplatin/pemetrexed is a well-tolerated regimen with activity in platinum-sensitive recurrent EOC; further testing of this regimen in platinum-sensitive EOC patients is warranted.
治疗铂敏感复发性上皮性卵巢癌（EOC）需要更有效、毒性更小的联合方案。培美曲塞是一种多靶点抗叶酸药物，毒性易于控制，已与卡铂联合用于治疗其他癌症。
这是一项II期研究，卡铂曲线下面积为5，培美曲塞500mg/m²于第1天静脉给药，每21天一次，共六个周期；若出现临床获益，则最多进行八个周期。符合条件的患者患有铂敏感复发性EOC、腹膜浆液性癌或输卵管癌。主要目的是根据实体瘤疗效评价标准确定缓解率；其他终点包括毒性、无进展生存期（PFS）和总生存期（OS）。
共纳入45例患者；44例患者接受了治疗。总缓解率为51.1%；无完全缓解（0%），23例确诊部分缓解（51.1%），2例未确诊部分缓解（4.4%），14例疾病稳定（31.1%），2例患者在两个周期后疾病进展（4.4%）。3级和4级血液学毒性包括中性粒细胞减少（41%）、血小板减少（23%）和贫血（9%）；无发热性中性粒细胞减少事件。3级和4级非血液学毒性包括疲劳（11%）、恶心（5%）、呕吐（5%）、腹泻（5%）、晕厥（5%）和肺栓塞（5%）。中位PFS时间为7.57个月（95%CI，6.44至10.18个月），平均OS时间为20.3个月，中位OS尚未达到，平均随访时间为15.3个月。
卡铂/培美曲塞是一种耐受性良好的方案，对铂敏感复发性EOC有活性；有必要在铂敏感EOC患者中对该方案进行进一步测试。
