Anderson H, Lund B, Bach F, Thatcher N, Walling J, Hansen H H
Manchester Lung Tumour Study Group, Wythenshawe Hospital, United Kingdom.
J Clin Oncol. 1994 Sep;12(9):1821-6. doi: 10.1200/JCO.1994.12.9.1821.
To evaluate the efficacy and safety of gemcitabine, a pyrimidine antimetabolite with activity against solid tumours.
Eighty-two patients with unresectable stage IIIa to IV non-small-cell lung cancer (NSCLC) were entered. The first 54 patients received gemcitabine 800 mg/m2, and subsequent patients 1,000 mg/m2, as a 30-minute intravenous infusion on days 0, 7, and 14. Courses of therapy were repeated every 28 days. Twenty percent dosage escalation was permitted after course no.1 if World Health Organization (WHO) toxicity was < or = 1.
Sixteen (20%; 95% confidence interval [CI], 12% to 31%) of 79 patients assessable for response had independently validated partial responses, with a median duration of 7 months. The overall median survival duration was 7 months. Gemcitabine improved disease-related symptoms (70% patients) and increased WHO performance status (44%). Toxicity was generally mild and reversible. Patients experienced little WHO grade 3 and 4 toxicity, with anemia in four (5%), thrombocytopenia in one (1%), leukopenia in six (7%), and neutropenia in 18 (22%). Infection occurred in nine patients (12%) during the study (four were neutropenic), but there were no episodes of WHO grade 3 or 4 infection. WHO grade 3 and 4 biochemical toxicity occurred with transient elevations of transaminases in 10 patients (12%). Two patients had transient WHO grade 3 elevation of serum creatinine levels, and two developed acute renal failure 4 and 6 weeks after the last dose of gemcitabine. There was no WHO grade 4 symptomatic toxicity. WHO grade 3 vomiting occurred in 31 patients (38%) and grade 3 alopecia in one (1%). Flu-like symptoms were associated with gemcitabine administration in 36 patients (44%). Twenty-six patients (32%) experienced fever (1% WHO grade 3), 33 (40%) ankle edema not associated with cardiac failure, 31 (38%) lethargy, and 11 (13%) dyspnea.
Gemcitabine is an active new agent in the treatment of NSCLC. This schedule was associated with little alopecia or myelosuppression. Gemcitabine warrants further investigation in other malignancies and in combination with other agents.
评估吉西他滨（一种对实体瘤有活性的嘧啶抗代谢物）的疗效和安全性。
纳入82例无法切除的Ⅲa期至Ⅳ期非小细胞肺癌（NSCLC）患者。前54例患者接受800mg/m²吉西他滨，后续患者接受1000mg/m²，于第0、7和14天静脉输注30分钟。每28天重复治疗疗程。如果世界卫生组织（WHO）毒性≤1级，允许在第1疗程后剂量增加20%。
79例可评估反应的患者中有16例（20%；95%置信区间[CI]，12%至31%）获得独立确认的部分缓解，中位缓解持续时间为7个月。总体中位生存时间为7个月。吉西他滨改善了与疾病相关的症状（70%的患者）并提高了WHO体能状态（44%）。毒性一般较轻且可逆。患者很少出现WHO 3级和4级毒性，4例（5%）出现贫血，1例（1%）出现血小板减少，6例（7%）出现白细胞减少，18例（22%）出现中性粒细胞减少。研究期间9例患者（12%）发生感染（4例为中性粒细胞减少），但无WHO 3级或4级感染事件。10例患者（12%）出现转氨酶短暂升高，发生WHO 3级和4级生化毒性。2例患者血清肌酐水平短暂出现WHO 3级升高，2例在最后一剂吉西他滨后4周和6周发生急性肾衰竭。无WHO 4级症状性毒性。31例患者（38%）出现WHO 3级呕吐，1例（1%）出现3级脱发。36例患者（44%）出现与吉西他滨给药相关的流感样症状。26例患者（32%）发热（1%为WHO 3级），33例（40%）出现与心力衰竭无关的踝部水肿，31例（38%）出现嗜睡，11例（13%）出现呼吸困难。
吉西他滨是治疗NSCLC的一种活性新药。该方案导致的脱发或骨髓抑制较少。吉西他滨值得在其他恶性肿瘤中以及与其他药物联合进一步研究。
