von der Maase H, Lehmann J, Gravis G, Joensuu H, Geertsen P F, Gough J, Chen G, Kania M
Department of Oncology, Aarhus University Hospital, Aarhus C, Denmark.
Ann Oncol. 2006 Oct;17(10):1533-8. doi: 10.1093/annonc/mdl154. Epub 2006 Jul 27.
Both pemetrexed and gemcitabine have single-agent activity in bladder cancer, but the combination of these two drugs has not been previously evaluated for safety and efficacy in this disease. Thus, the objectives in the current study were to determine overall response rate (ORR), progression-free survival, overall survival and safety and toxicity in chemonaive patients with locally advanced and/or metastatic transitional cell carcinoma of the urothelium.
Gemcitabine 1250 mg/m2 was administered over 30 min i.v. on days 1 and 8, and pemetrexed 500 mg/m2 over 10 min i.v. on day 8 after gemcitabine, every 21 days.
Sixty-four patients were enrolled, 11 female and 53 male, median age 65 years (range 38-81), median WHO performance status of 1. Visceral metastases were present in 55% of patients. ORR among 47 patients evaluable for response was 28% (95% CI 16% to 43%) and ORR for the intention-to-treat population was 20% (95% CI 11% to 32%) with three CR and 10 PR. Median response duration was 11.2 months and median overall survival 10.3 months (95% CI 8.1-14.6 months). CTC grade 3/4 hematologic toxicities included anemia (19%), thrombocytopenia (9%), neutropenia (38%), febrile neutropenia (17%) and neutropenic sepsis (3%). Grade 3/4 non-hematologic toxicities included elevated transaminases (12%), dyspnea (8%), fatigue (8%) and stomatitis (5%). There was one toxic death due to neutropenic sepsis.
The combination of pemetrexed and gemcitabine had a manageable safety profile. However, efficacy was apparently not superior to that of single-agent gemcitabine.
培美曲塞和吉西他滨在膀胱癌中均具有单药活性，但这两种药物联合应用于该疾病的安全性和疗效此前尚未得到评估。因此，本研究的目的是确定初治的局部晚期和/或转移性尿路上皮移行细胞癌患者的总缓解率（ORR）、无进展生存期、总生存期以及安全性和毒性。
吉西他滨1250mg/m²于第1天和第8天静脉滴注30分钟，培美曲塞500mg/m²在吉西他滨给药后的第8天静脉滴注10分钟，每21天重复一次。
共纳入64例患者，其中女性11例，男性53例，中位年龄65岁（范围38 - 81岁），世界卫生组织体能状态中位数为1。55%的患者存在内脏转移。47例可评估缓解情况的患者的ORR为28%（95%CI 16%至43%），意向性治疗人群的ORR为20%（95%CI 11%至32%），有3例完全缓解和10例部分缓解。中位缓解持续时间为11.2个月，中位总生存期为10.3个月（95%CI 8.1 - 14.6个月）。常见毒性标准（CTC）3/4级血液学毒性包括贫血（19%）、血小板减少（9%）、中性粒细胞减少（38%）、发热性中性粒细胞减少（17%）和中性粒细胞减少性败血症（3%）。3/4级非血液学毒性包括转氨酶升高（12%）、呼吸困难（8%）、疲劳（8%）和口腔炎（5%）。有1例因中性粒细胞减少性败血症导致的毒性死亡。
培美曲塞和吉西他滨联合应用具有可控的安全性。然而，疗效显然并不优于单药吉西他滨。
