Shepherd F A, Cormier Y, Burkes R, Evans W K, Goss G, Klimo P, Feld R, Taylor M
Department of Medicine, The Toronto Hospital, Ontario, Canada.
Semin Oncol. 1997 Jun;24(3 Suppl 8):S8-27-S8-30.
Single-agent gemcitabine, when given in doses of > or = 1,250 mg/m2 weekly x 3 with a 1-week break, induces responses in approximately 20% of untreated patients with non-small cell lung cancer. This phase II study was undertaken to determine the efficacy of weekly administration of gemcitabine 1,500 mg/m2 combined with cisplatin 30 mg/m2 x 3 with a rest period of 1 week. Patients younger than 75 years were eligible if they had stage III/IV non-small cell lung cancer, a life expectancy > or = 12 weeks, hemoglobin > or = 10 g/dL, absolute granulocyte count > or = 10(9)/L, platelets > or = 100 x 10(9)/L, hepatic enzymes no more than three times the upper limit of normal, and serum creatinine < or = 130 micromol/L. There were 22 men and 18 women, with a median age of 60 years; 35 had a performance status of 0 or 1. Pathology included adenocarcinoma in 22 patients, squamous cell carcinoma in nine, large cell carcinoma in seven, and mixed non-small cell lung cancer in two. Six patients had stage III and 34 had stage IV tumors. Of the 39 patients eligible for response evaluation, partial remission was seen in 10, for an overall response rate of 26% (95% confidence interval, 12% to 41%). The median duration of response was 19 weeks (range, 7 to 32+ weeks). Grade 3/4 anemia was seen in 11 patients, and 21 patients required red blood cell transfusions. Grade 3/4 neutropenia occurred in 22 patients and grade 3/4 thrombocytopenia in 21 patients. One patient experienced febrile neutropenia Hematologic toxicity, particularly thrombocytopenia, was cumulative over time. Nonhematologic toxicity was modest, but one patient stopped therapy because of a grade 2 skin rash and one stopped because of a grade 4 pulmonary toxicity, both of which were thought to be related to gemcitabine. The modest activity of weekly gemcitabine and weekly cisplatin seen in this trial does not suggest in vivo synergy for these two agents as administered using this schedule and these doses.
单药吉西他滨，当以≥1250mg/m²的剂量每周给药1次，共3周，休息1周时，可使约20%未经治疗的非小细胞肺癌患者产生反应。本II期研究旨在确定每周给予1500mg/m²吉西他滨联合30mg/m²顺铂，共3周，休息1周的疗效。年龄小于75岁、患有III/IV期非小细胞肺癌、预期寿命≥12周、血红蛋白≥10g/dL、绝对粒细胞计数≥1×10⁹/L、血小板≥100×10⁹/L、肝酶不超过正常上限3倍且血清肌酐≤130μmol/L的患者符合入选标准。入组患者中男性22例，女性18例，中位年龄60岁；35例患者的体能状态为0或1。病理类型包括腺癌22例、鳞癌9例、大细胞癌7例、混合性非小细胞肺癌2例。6例患者为III期肿瘤，34例为IV期肿瘤。在39例符合疗效评估标准的患者中，10例出现部分缓解，总缓解率为26%（95%置信区间为12%至41%）。缓解持续时间的中位数为19周（范围为7至32+周）。11例患者出现3/4级贫血，21例患者需要输注红细胞。22例患者出现3/4级中性粒细胞减少，21例患者出现3/4级血小板减少。1例患者发生发热性中性粒细胞减少。血液学毒性，尤其是血小板减少，随时间累积。非血液学毒性较轻，但1例患者因2级皮疹停止治疗，1例因4级肺部毒性停止治疗，二者均被认为与吉西他滨有关。本试验中观察到的每周使用吉西他滨和顺铂的疗效一般，并不表明按照此方案和剂量给药时这两种药物在体内具有协同作用。
