Feliu J, Martin G, Lizón J, Chacón J I, Dorta J, de Castro J, Rodríguez A, Sánchez Heras B, Torrego J C, Espinosa E, González Barón M
Servicio de Oncología Médica, Hospitals La Paz, Madrid, Spain.
Ann Oncol. 2001 Oct;12(10):1369-74. doi: 10.1023/a:1012552525667.
New effective therapies are needed to improve the outcome of patients with advanced non-small-cell lung cancer (NSCLC). The aim of this study was to assess the response rate and survival obtained with a sequential regimen of chemotherapy.
Patients with newly diagnosed stage IIIb-IV NSCLC were included. They all had measurable disease and a good performance status (0-2 in the Eastern Cooperative Oncology Group scale). Chemotherapy consisted of weekly paclitaxel 150 mg/m2 x 6, followed two weeks later by cisplatin 100 mg/m2 on day 1, gemcitabine 1,000 mg/m2 on days 1 and 14, and vinorelbine 25 mg/m2 on days 1 and 14 (CGV). CGV was administered every 28 days for a maximum of six courses.
Fifty-two patients were included, 19 (37%) with stage IIIb and 33 (63%) with stage IV disease. After therapy with weekly paclitaxel. 29 partial responses were obtained (56%, 95% confidence interval (95% CI): 38%-67%), whereas 15 patients had stable disease (29%) and eight had a progression (15%). After CGV, there were four complete remissions (8%) and 24 partial responses (46%), for an overall response rate of 54% (95% CI: 37%-65%). Eight patients had stable disease (15%) and 16 had a progression (31%). No patient progressing after paclitaxel responded to CGV, whereas 5 out of 15 patients with stable disease reached a partial response with CGV (33%). On the contrary, 5 out of 29 patients with a partial response to paclitaxel progressed after CGV (17%). Median survival has not been reached after a median follow-up of 14 months. Median time to progression was nine months. Fifty-six percent of patients remain alive at one year. Two hundred eighty-nine courses of paclitaxel and 170 of CGV were given, with a median of 5.5 and 3.4 per patient, respectively (ranges 2-6 and 0-6. respectively). WHO grade 3-4 toxicities for paclitaxel were: neutropenia in two patients (4/) and peripheral neuropathy in five (10%). Two patients had allergic reactions requiring paclitaxel withdrawal, whereas four (8%) had hyperglycemia >250 mg/ml. Grade 3-4 toxicities for CGV were: neutropenia in ten patients (20%), peripheral neuropathy in six (12%), anemia in four (8%), nausea/vomiting in five (10%). thrombocytopenia in two (4%), and fatigue in four (8%).
Our results suggest that sequential chemotherapy with weekly paclitaxel followed by CGV is highly active in patients with advanced NSCLC and has an acceptable toxicity. This schedule deserves further evaluation in a phase III study.
需要新的有效疗法来改善晚期非小细胞肺癌（NSCLC）患者的预后。本研究的目的是评估序贯化疗方案的缓解率和生存率。
纳入新诊断的Ⅲb-Ⅳ期NSCLC患者。他们均有可测量病灶且体能状态良好（东部肿瘤协作组量表评分为0-2）。化疗方案为每周一次紫杉醇150mg/m²，共6周，两周后第1天给予顺铂100mg/m²，第1天和第14天给予吉西他滨1000mg/m²，第1天和第14天给予长春瑞滨25mg/m²（CGV方案）。CGV方案每28天进行一次，最多6个疗程。
共纳入52例患者，其中19例（37%）为Ⅲb期，33例（63%）为Ⅳ期。每周使用紫杉醇治疗后，获得29例部分缓解（56%，95%置信区间（95%CI）：38%-67%），15例患者病情稳定（29%），8例病情进展（15%）。CGV方案治疗后，有4例完全缓解（8%）和24例部分缓解（46%），总缓解率为54%（95%CI：37%-65%）。8例患者病情稳定（15%），16例病情进展（31%）。紫杉醇治疗后病情进展的患者对CGV方案均无反应，而15例病情稳定的患者中有5例（33%）经CGV方案治疗后达到部分缓解。相反，29例对紫杉醇治疗有部分缓解的患者中有5例（17%）在CGV方案治疗后病情进展。中位随访14个月后，中位生存期尚未达到。中位疾病进展时间为9个月。56%的患者1年时仍存活。共给予289个疗程的紫杉醇和170个疗程的CGV方案，每位患者的中位数分别为5.5个和3.4个疗程（范围分别为2-6个和0-6个疗程）。紫杉醇的WHO 3-4级毒性反应为：2例患者（4%）出现中性粒细胞减少，5例患者（10%）出现周围神经病变。2例患者出现过敏反应，需要停用紫杉醇，4例患者（8%）血糖>250mg/ml。CGV方案的3-4级毒性反应为：10例患者（20%）出现中性粒细胞减少，6例患者（12%）出现周围神经病变，4例患者（8%）出现贫血，5例患者（10%）出现恶心/呕吐，2例患者（4%）出现血小板减少，4例患者（8%）出现疲劳。
我们的结果表明，先每周使用紫杉醇序贯CGV方案的化疗对晚期NSCLC患者具有高活性且毒性可接受。该方案值得在Ⅲ期研究中进一步评估。
