Takada M, Negoro S, Kudo S, Furuse K, Nishikawa H, Takada Y, Kamei T, Niitani H, Fukuoka M
Pulmonary Medicine, Rinku General Medical Center, Izumisano-city, Osaka, Japan.
Cancer Chemother Pharmacol. 1998;41(3):217-22. doi: 10.1007/s002800050731.
This phase II study was conducted to determine the response and toxicity of gemcitabine (2',2'-difluorodeoxycytidine) in chemotherapy-naive patients with non-small-cell lung cancer (NSCLC).
A group of 73 patients were entered into the study. The patients had received no previous chemotherapy and all had measurable disease. The initial starting dose of gemcitabine was 1000 mg/m2 per week x 3 followed by a week of rest, and was escalated for the next cycle to 1250 mg/m2, provided there were no signs of hematologic toxicity (WBC < 3000/microl and/or platelets < 70,000/microl) in the previous cycle.
Among 73 eligible patients, there were 19 partial responses (PRs), with an overall response rate of 26.0% (95% confidence interval 16.5-37.6%). The response rate for stage IIIa and IIIb disease was significantly higher than that for stage IV disease [41.4% (12/29) vs 15.9% (7/44); P = 0.028]. The median duration of response in patients showing a PR was 4.6 months (1.7 10.4 months). The median number of cycles given was two per patient (range one to seven). Grade 3 anemia, leukopenia and neutropenia occurred in 15 patients (20.5%), 7 patients (9.6%) and 20 patients (27.4%), respectively. Grade 3 thrombocytopenia occurred in one patient (1.4%) which was not associated with any bleeding. There was no evidence of cumulative toxicity in the later courses of gemcitabine treatment with regard to leukopenia and thrombocytopenia. Other toxicities, including hepatic toxicity, fatigue, nausea/vomiting and fever were mild (grade 2 or less) and transient. One patient was withdrawn from the trial because of a rash. Pulmonary toxicity was experienced in two patients and one patient died of respiratory insufficiency which was thought to be drug-related.
Gemcitabine as a single agent has proven to be an active drug for NSCLC with a favorable, generally mild side-effect profile. Further trials in combination with other agents for this disease are currently underway.
本II期研究旨在确定吉西他滨（2',2'-二氟脱氧胞苷）对未经化疗的非小细胞肺癌（NSCLC）患者的疗效和毒性。
73例患者进入本研究。这些患者之前未接受过化疗，且均有可测量的病灶。吉西他滨的初始起始剂量为每周1000mg/m²，共3周，随后休息1周；如果前一周期没有血液学毒性迹象（白细胞计数<3000/μl和/或血小板计数<70,000/μl），则下一周期剂量增至1250mg/m²。
73例符合条件的患者中，有19例部分缓解（PR），总缓解率为26.0%（95%置信区间16.5 - 37.6%）。IIIa期和IIIb期疾病的缓解率显著高于IV期疾病[41.4%（12/29）对15.9%（7/44）；P = 0.028]。显示PR的患者的中位缓解持续时间为4.6个月（1.7 - 10.4个月）。每位患者给予的中位周期数为2个（范围1至7个）。15例患者（20.5%）发生3级贫血，7例患者（9.6%）发生3级白细胞减少，20例患者（27.4%）发生3级中性粒细胞减少。1例患者（1.4%）发生3级血小板减少，但未出现任何出血情况。在吉西他滨治疗的后期疗程中，未发现白细胞减少和血小板减少的累积毒性证据。其他毒性，包括肝毒性、疲劳、恶心/呕吐和发热均较轻（2级或以下）且为一过性。1例患者因皮疹退出试验。2例患者出现肺部毒性，1例患者死于呼吸功能不全，认为与药物相关。
吉西他滨作为单一药物已被证明是一种对NSCLC有效的药物，副作用总体较轻。目前正在进行该药与其他药物联合治疗该疾病的进一步试验。
