Gridelli Cesare, De Maio Ermelinda, Barbera Santi, Sannicolo Mirella, Piazza Elena, Piantedosi FrancoVito, Brancaccio Luigi, Morabito Alessandro, Maione Paolo, Renda Francesco, Signoriello Giuseppe, Perrone Francesco
Medical Oncology, S. Giuseppe Moscati Hospital, Avellino, Italy.
Lung Cancer. 2008 Jul;61(1):67-72. doi: 10.1016/j.lungcan.2007.12.002.
Gemcitabine has been widely studied in elderly patients affected by advanced non-small cell lung cancer (NSCLC). A prolonged constant infusion (10 mg/m2/min) has been proposed as a way to improve its efficacy. Aim of this study is to describe activity and toxicity of single-agent gemcitabine given as prolonged infusion in the treatment of elderly patients with advanced NSCLC.
Patients aged 70 years or older, with stage IV or IIIB (effusion/supraclavicular nodes) NSCLC, good performance status (0 or 1 according to ECOG classification) who had never received chemotherapy were eligible. Gemcitabine was administered at the dose of 1200 mg/m2 by prolonged infusion (10 mg/m2/min) on days 1 and 8 of each cycle. Courses were repeated every 21 days, for a maximum of 6 cycles, unless disease progression or severe toxicity. A single stage phase 2 design was applied, with 51 patients required to estimate a 25% +/- 10% response rate. Ten responses were required to define the treatment as active.
Fifty-one patients were enrolled, with a median age of 76 years (range 70-83). Two complete responses and seven partial responses were observed, for an overall response rate of 17.6% (95% exact C.I.: 8.4-30.9%). The median time to disease progression was 16.1 weeks (95% C.I.: 11.1-20.6) and the median overall survival was 41.3 weeks (95% C.I.: 27.6-50.6). There were 2 toxic deaths, due to bleeding and liver toxicity, and one patient had an ischemic stroke. Other non-haematological toxicities were: fatigue (44% of patients), grade 2-3 pulmonary toxicity (8%), grade 2-3 hepatic toxicity (16%). Nausea and stomatitis were mild and no cases of cardiac toxicity were observed. Haematological toxicity was mild, with no case of febrile neutropenia.
Gemcitabine at prolonged constant infusion produced a response rate lower than that required by study design and should no longer be of interest for the treatment of elderly patients with advanced NSCLC.
吉西他滨已在老年晚期非小细胞肺癌（NSCLC）患者中得到广泛研究。有人提出延长持续输注（10mg/m²/分钟）是提高其疗效的一种方法。本研究的目的是描述在老年晚期NSCLC患者治疗中，采用延长输注方式给予单药吉西他滨的活性和毒性。
年龄70岁及以上、患有IV期或IIIB期（有胸腔积液/锁骨上淋巴结转移）NSCLC、体能状态良好（根据东部肿瘤协作组[ECOG]分类为0或1）且从未接受过化疗的患者符合入选标准。在每个周期的第1天和第8天，通过延长输注（10mg/m²/分钟）给予吉西他滨，剂量为1200mg/m²。每21天重复一个疗程，最多6个疗程，除非疾病进展或出现严重毒性。采用单阶段2期设计，需要51例患者来估计25%±10%的缓解率。需要10例缓解才能确定该治疗方案具有活性。
共纳入51例患者，中位年龄76岁（范围70 - 83岁）。观察到2例完全缓解和7例部分缓解，总缓解率为17.6%（95%确切置信区间：8.4 - 30.9%）。疾病进展的中位时间为16.1周（95%置信区间：11.1 - 20.6），中位总生存期为41.3周（95%置信区间：27.6 - 50.6）。有2例因出血和肝毒性导致的毒性死亡，1例患者发生缺血性中风。其他非血液学毒性包括：疲劳（44%的患者）、2 - 3级肺部毒性（8%）、2 - 3级肝毒性（16%）。恶心和口腔炎较轻，未观察到心脏毒性病例。血液学毒性较轻，无发热性中性粒细胞减少病例。
延长持续输注的吉西他滨产生的缓解率低于研究设计要求，不应再作为老年晚期NSCLC患者治疗的选择。
