A phase III trial of pemetrexed plus gemcitabine versus gemcitabine in patients with unresectable or metastatic pancreatic cancer
A phase III trial of pemetrexed plus gemcitabine versus gemcitabine in patients with unresectable or metastatic pancreatic cancer
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DOI：
10.1093/annonc/mdi309
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发表时间：
2005-10-01
影响因子：
50.5
通讯作者：
Kindler, HL
中科院分区：
文献类型：
--
作者：
Oettle, H;Richards, D;Kindler, HL
背景：这项随机Ⅲ期研究比较了培美曲塞联合吉西他滨（PG）与标准吉西他滨（G）在晚期胰腺癌患者中的总生存期（OS）。
患者与方法：患有不可切除的局部晚期或转移性胰腺癌且既往未接受过全身治疗（包括作为放射增敏剂的5 - 氟尿嘧啶）的患者被随机分组，在每个21天周期的第1天和第8天接受1250 mg/m²吉西他滨，并且在第8天吉西他滨之后接受500 mg/m²培美曲塞（PG组），或者在每个28天周期的第1、8和15天接受1000 mg/m²吉西他滨（G组）。
结果：565例基线特征均衡良好的患者被随机分配（283例至PG组，282例至G组）。与G组（6.3个月）相比，PG组的OS（6.2个月）未得到改善（P = 0.8477）。无进展生存期（3.9个月对3.3个月；P = 0.1109）和治疗失败时间（3个月对2.2个月；P = 0.2680）结果相似。PG组的肿瘤缓解率（14.8%对7.1%；P = 0.004）显著更好。3级或4级中性粒细胞减少症（45.1%对12.8%）、血小板减少症（17.9%对6.2%）、贫血（13.9%对2.9%）、发热性中性粒细胞减少症（9.9%对0.4%；所有P < 0.001）以及疲劳（15%对6.6%；P = 0.002）在PG组明显更常见。PG组发生了4例治疗相关死亡，G组无相关死亡。
结论：培美曲塞联合吉西他滨治疗未改善总生存期。单药吉西他滨仍然是晚期胰腺癌的标准治疗方法。
Background: This randomized phase III study compared the overall survival (OS) of pemetrexed plus gemcitabine (PG) versus standard gemcitabine (G) in patients with advanced pancreatic cancer.Patients and methods: Patients with unresectable locally advanced or metastatic pancreatic cancer and no prior systemic therapy (including 5-fluorouracil as a radiosensitizer) were randomized to receive either 1250 mg/m(2) gemcitabine on days 1 and 8 plus pemetrexed 500 mg/m(2) after gemcitabine on day 8 (PG arm) of each 21-day cycle, or gemcitabine 1000 mg/m(2) on days 1, 8 and 15 of each 28-day cycle (G arm).Results: Five hundred and sixty-five patients with well-balanced baseline characteristics were randomly assigned (283 PG, 282 G). OS was not improved on the PG arm (6.2 months) compared with the G arm (6.3 months) (P = 0.8477). Progression-free survival (3.9 versus 3.3 months; P = 0.1109) and time to treatment failure (3 versus 2.2 months; P = 0.2680) results were similar. Tumor response rate (14.8% versus 7.1%; P = 0.004) was significantly better on the PG arm. Grade 3 or 4 neutropenia (45.1% versus 12.8%), thrombocytopenia (17.9% versus 6.2%), anemia (13.9% versus 2.9%), febrile neutropenia (9.9% versus 0.4%; all P < 0.001) and fatigue (15% versus 6.6%; P = 0.002) were significantly more common on the PG arm. Four treatment-related deaths occurred on the PG arm and none in the G arm.Conclusions: Pemetrexed plus gemcitabine therapy did not improve OS. Single-agent gemcitabine remains the standard of care for advanced pancreatic cancer.