Gridelli Cesare, Kaukel Eckhard, Gregorc Vanessa, Migliorino Maria Rita, Müller Thomas R, Manegold Christian, Favaretto Adolfo, Martoni Andrea, Caffo Orazio, Schmittel Alexander, Rossi Antonio, Russo Francesca, Peterson Patrick, Muñoz María, Reck Martin
Division of Medical Oncology, S.G. Moscati Hospital, Avellino, Italy.
J Thorac Oncol. 2007 Mar;2(3):221-9. doi: 10.1097/JTO.0b013e318031cd62.
This randomized phase II trial evaluated single-agent pemetrexed or sequential pemetrexed/gemcitabine in patients with non-small cell lung cancer (NSCLC) who were elderly (> or = 70 years) or younger than 70 years and ineligible for platinum-based chemotherapy.
Chemonaive patients with stage IIIB/IV NSCLC and an Eastern Cooperative Oncology Group performance status of 0 to 2 received either 500 mg/m2 of pemetrexed (day 1, every 3 weeks) for eight cycles, or the same dosage of pemetrexed for cycles 1 and 2 and then 1200 mg/m2 of gemcitabine (days 1 and 8, every 3 weeks) for cycles 3 and 4 (repeated once for a total of eight cycles). All patients were given vitamin B12 and folic acid supplementation.
From July 2003 to July 2004, 87 patients (44 pemetrexed; 43 pemetrexed/gemcitabine) received treatment. The median time to progression was 4.5 (95% confidence interval: 3.0-9.3) and 4.1 months (95% confidence interval: 1.7-5.8) for the pemetrexed and pemetrexed/gemcitabine arms, respectively, and the median progression-free survival time was 3.3 months for both arms. Tumor response rates for the pemetrexed and pemetrexed/gemcitabine arms were 4.5% and 11.6%, respectively. The median overall survival time was 4.7 months for the pemetrexed arm and 5.4 months for the pemetrexed/gemcitabine arm, with respective 1-year survival rates of 28.5% and 28.1%. Grade 3/4 hematologic toxicity consisted of neutropenia (4.5% pemetrexed; 2.3% pemetrexed/gemcitabine), febrile neutropenia (4.5% pemetrexed; 4.7% pemetrexed/gemcitabine), thrombocytopenia (4.5% pemetrexed; 7.0% pemetrexed/gemcitabine), and anemia (6.8% pemetrexed; 4.7% pemetrexed/gemcitabine). No grade 3/4 nonhematologic toxicities exceeded 4.7% in either arm.
Single-agent pemetrexed and sequential pemetrexed/gemcitabine have shown moderate activity and are well tolerated as first-line treatments for advanced NSCLC in elderly patients or patients unsuitable for platinum-based combination chemotherapy.
本随机II期试验评估了单药培美曲塞或序贯培美曲塞/吉西他滨用于老年（≥70岁）或小于70岁且不符合铂类化疗条件的非小细胞肺癌（NSCLC）患者的疗效。
初治的IIIB/IV期NSCLC患者，东部肿瘤协作组体能状态为0至2，接受500mg/m²培美曲塞（第1天，每3周一次）共8个周期，或第1和2周期使用相同剂量培美曲塞，然后第3和4周期使用1200mg/m²吉西他滨（第1和8天，每3周一次）（重复一次，共8个周期）。所有患者均补充维生素B12和叶酸。
2003年7月至2004年7月，87例患者（44例接受培美曲塞治疗；43例接受培美曲塞/吉西他滨治疗）接受了治疗。培美曲塞组和培美曲塞/吉西他滨组的中位疾病进展时间分别为4.5个月（95%置信区间：3.0 - 9.3）和4.1个月（95%置信区间：1.7 - 5.8），两组的中位无进展生存期均为3.3个月。培美曲塞组和培美曲塞/吉西他滨组的肿瘤缓解率分别为4.5%和11.6%。培美曲塞组的中位总生存期为4.7个月，培美曲塞/吉西他滨组为5.4个月，1年生存率分别为28.5%和28.1%。3/4级血液学毒性包括中性粒细胞减少（培美曲塞组4.5%；培美曲塞/吉西他滨组2.3%）、发热性中性粒细胞减少（培美曲塞组4.5%；培美曲塞/吉西他滨组4.7%）、血小板减少（培美曲塞组4.5%；培美曲塞/吉西他滨组7.0%）和贫血（培美曲塞组6.8%；培美曲塞/吉西他滨组4.7%）。两组中3/4级非血液学毒性均未超过4.7%。
单药培美曲塞和序贯培美曲塞/吉西他滨已显示出适度活性，作为老年患者或不适合铂类联合化疗患者晚期NSCLC的一线治疗耐受性良好。
