Abratt R P, Bezwoda W R, Falkson G, Goedhals L, Hacking D, Rugg T A
Department of Oncology, University of Cape Town, South Africa.
J Clin Oncol. 1994 Aug;12(8):1535-40. doi: 10.1200/JCO.1994.12.8.1535.
The aim of this study was to evaluate the efficacy and toxicity of gemcitabine at higher doses than had been used previously in patients with non-small-cell lung cancer (NSCLC).
Eighty-four patients (65 men, 19 women; age range, 35 to 75 years; mean age, 59 years) with locally advanced or metastatic pathologically documented NSCLC were enrolled. Patients had bidimensionally measurable disease, as defined by computed tomographic (CT) scan or chest x-ray. A total of 28.6% had previously been surgically treated, while 9.5% had received radiotherapy. Fifty-three patients commenced at a dose of 1,000 mg/m2, and 31 at a dose of 1,250 mg/m2. Patients were to receive two dose escalations of 25%, provided that overall toxicity was no worse than World Health Organization (WHO) grade 1 or WHO grade 0 for platelets. Responding patients were reviewed and validated by a blinded oncology review board (ORB) of experts not involved with the study. Of the original 84 patients enrolled, 76 were assessable.
The overall response rate was 20% (95% confidence interval [CI], 11.6% to 30.8%). There were two complete responses (3%) and 13 partial responses (17%). Hematologic toxicity was negligible. WHO grade 3 WBC toxicity occurred in 0.9% of doses and WHO grade 4 in 0.1%. WHO grade 3 and 4 thrombocytopenia occurred in 0.1% and 0.1% of all doses, respectively. Nonhematologic toxicity was minor and easily controlled. Common side effects included peripheral edema, asthenia, and transient malaise.
The single-agent efficacy of gemcitabine is equivalent to other agents commonly used to treat NSCLC. Gemcitabine has an unusually mild side effect profile for such an active agent. The nausea and vomiting experienced with gemcitabine are mild and generally well controlled with standard antiemetics; 5-HT3 receptor antagonists are typically not required. The use of gemcitabine does not cause significant alopecia, and hematologic toxicity is modest and unlikely to require hospitalization. Gemcitabine may have a role as monotherapy in patients with inoperable NSCLC.
本研究旨在评估吉西他滨在高于既往用于非小细胞肺癌（NSCLC）患者剂量时的疗效和毒性。
纳入84例经病理证实为局部晚期或转移性NSCLC的患者（65例男性，19例女性；年龄范围35至75岁；平均年龄59岁）。患者具有通过计算机断层扫描（CT）或胸部X线定义的可二维测量的疾病。共有28.6%的患者既往接受过手术治疗，9.5%的患者接受过放疗。53例患者起始剂量为1000mg/m²，31例患者起始剂量为1250mg/m²。只要总体毒性不超过世界卫生组织（WHO）1级或血小板WHO 0级，患者将接受两次25%的剂量递增。缓解患者由未参与该研究的盲态肿瘤学专家评审委员会（ORB）进行复查和确认。在最初纳入的84例患者中，76例可评估。
总体缓解率为20%（95%置信区间[CI]，11.6%至30.8%）。有2例完全缓解（3%）和13例部分缓解（17%）。血液学毒性可忽略不计。WHO 3级白细胞毒性在0.9%的剂量中出现，WHO 4级在0.1%的剂量中出现。WHO 3级和4级血小板减少分别在所有剂量的0.1%和0.1%中出现。非血液学毒性轻微且易于控制。常见副作用包括外周水肿、乏力和短暂不适。
吉西他滨的单药疗效与常用于治疗NSCLC的其他药物相当。对于这样一种活性药物，吉西他滨具有异常轻微的副作用谱。吉西他滨引起的恶心和呕吐较轻，通常用标准止吐药就能很好地控制；通常不需要5 - HT3受体拮抗剂。使用吉西他滨不会导致明显脱发，血液学毒性较小，不太可能需要住院治疗。吉西他滨在无法手术的NSCLC患者中可能具有单药治疗的作用。
