Antón A, Díaz-Fernández N, González Larriba J L, Vadell C, Masutti B, Montalar J, Barneto I, Artal A, Rosell R
Hospital Miguel Servet de Zaragoza, Servicio de Oncología Médica, Zaragoza, Spain.
Lung Cancer. 1998 Nov;22(2):139-48. doi: 10.1016/s0169-5002(98)00069-5.
There is need for more active and better tolerated combinations in non-small cell lung cancer (NSCLC). The Spanish Lung Cancer Group (SLCG) therefore conducted this phase II study to define the efficacy and toxicity profile of the combination of higher doses than usual of gemcitabine along with cisplatin in patients with advanced NSCLC.
Forty patients with pathologically documented advanced NSCLC were included in this trial (34 men, six women; aged 34-74 years; mean 64 years). Twenty-two patients had unresectable stage IIIB disease and 18 had stage IV disease. Karnofsky performance status was > or =70%. In five patients, surgery had previously been performed and four patients had received radiotherapy. Gemcitabine at a dose of 1200 mg/m2 was administered weekly (days 1, 8 and 15) and cisplatin 100 mg/m2 on day 15 of each 28-day cycle.
Responses were scored according to standard World Health Organization criteria. Of 40 assessable patients, 19 had a partial response for an overall response rate of 47.5% (95% confidence interval (CI) 32-64%). To date, median survival for the whole group is 10.4 months (95% CI 6.2-11.7 months), with a 1-year survival rate of 35%. Toxicity was mainly haematological. Seven patients (18%) had grade 4 neutropenia (one episode of febrile neutropenia). Thrombocytopenia (12.8% grade 3 and 2.6% grade 4) was not associated with clinical bleeding. One patient had a grade 4 transient rise in transaminase. There was no grade 3 or 4 renal toxicity. There was no grade 4 symptomatic toxicity. The most common grade 3 toxicities were nausea and vomiting (28.2%) and alopecia (10.3%) both related to cisplatin.
Gemcitabine can be safely administered at a dose of 1200 mg/m2 in combination with cisplatin. Thrombocytopenia seems to be less than in schedules with cisplatin given on day 1. The results of this studyshow promising activity (47.5% response rate) with modest toxicity. As this combination of gemcitabine and cisplatin deserves further evaluation in prospective randomized trials, the SLCG is comparing gemcitabine-cisplatin with etoposide-cisplatin in a phase III randomized study.
非小细胞肺癌（NSCLC）需要更积极且耐受性更好的联合治疗方案。因此，西班牙肺癌研究组（SLCG）开展了这项II期研究，以确定在晚期NSCLC患者中，高于常规剂量的吉西他滨联合顺铂的疗效和毒性特征。
本试验纳入了40例经病理证实的晚期NSCLC患者（34例男性，6例女性；年龄34 - 74岁；平均64岁）。22例患者为不可切除的IIIB期疾病，18例为IV期疾病。卡氏评分≥70%。5例患者此前接受过手术，4例患者接受过放疗。吉西他滨剂量为1200 mg/m²，每周给药（第1、8和15天），顺铂100 mg/m²在每28天周期的第15天给药。
根据世界卫生组织标准对疗效进行评分。在40例可评估患者中，19例有部分缓解，总缓解率为47.5%（95%置信区间[CI] 32 - 64%）。迄今为止，全组患者的中位生存期为10.4个月（95% CI 6.2 - 11.7个月），1年生存率为35%。毒性主要为血液学毒性。7例患者（18%）出现4级中性粒细胞减少（1例发热性中性粒细胞减少）。血小板减少（3级为12.8%，4级为2.6%）与临床出血无关。1例患者转氨酶出现4级短暂升高。无3级或4级肾毒性。无4级有症状毒性。最常见的3级毒性为恶心和呕吐（28.2%）以及脱发（10.3%），均与顺铂有关。
吉西他滨剂量为1200 mg/m²与顺铂联合使用可安全给药。血小板减少似乎比第1天给予顺铂的方案少。本研究结果显示出有前景的活性（缓解率47.5%）且毒性适中。由于吉西他滨与顺铂的这种联合方案值得在前瞻性随机试验中进一步评估，SLCG正在一项III期随机研究中比较吉西他滨 - 顺铂与依托泊苷 - 顺铂。
