Reck Martin, Macha Hans-Nikol, Del Barco Sonia, Cornes Paul, Vaissière Nathalie, Morand Maryse, Riggi Marcello, Abratt Raymond
Krankenhaus Grosshansdorf, Thoracic Oncology, D-22927 Grosshansdorf, Germany.
Lung Cancer. 2009 Jun;64(3):319-25. doi: 10.1016/j.lungcan.2008.10.014. Epub 2008 Dec 17.
This phase II study assessed the efficacy and safety of oral vinorelbine given weekly in combination with carboplatin (CBDCA) AUC 5 once every 3 weeks for four cycles in chemonaive patients with advanced non-small cell lung carcinoma (NSCLC), followed by consolidation therapy with single-agent oral vinorelbine in non-progressive patients.
Chemonaive advanced NSCLC patients received four cycles of combination therapy with CBDCA AUC 5 day 1 and oral vinorelbine, 60 mg/m2 on days 1, 8 and 15 (cycle 1), dose increased to 80 mg/m2 (cycles 2-4) in absence of grades 3-4 neutropenia (NCI-CTCv2). Consolidation therapy with oral vinorelbine was continued (cycle 5) at same dosage; if dose was decreased during combination therapy, it was given at 60 mg/m2, then increased at 80 mg/m2 (cycle 6) in absence of grades 3-4 neutropenia until PD, toxicity or patient's refusal.
A total of 57 patients were registered and 56 patients were treated (ITT population), median age was 61 years (37-71). Objective response evaluated by RECIST was 17.9% (95% confidence interval, CI [8.9-30.4]) and disease control (CR, PR, NC) 73.2% (95% CI [59.7-84.2]), median progression-free survival 4.3 months (95% CI [3.1-5.1]) with median overall survival 9.7 months (95% CI [7.7-11.9]) and 1-year survival 37.1% (95% CI [24.4, 49.9]). Grades 3-4 neutropenia occurred in 67.9% of patients during combination and 20% during consolidation; febrile neutropenia occurred in 4 patients (7.1%) during combination therapy. Non-hematological toxicities occurred primarily during combination (grade 3 nausea and grade 3 vomiting in 7.1% of patients).
The combination of oral vinorelbine given weekly in 3-week cycles in combination with carboplatin followed by consolidation therapy with oral vinorelbine as a single-agent was able to achieve efficacy results in line with other doublets including carboplatin in terms of response as well as survival. This regimen reported a good profile of tolerability in the treatment of advanced NSCLC, allowing that this combination can be easily proposed for the palliative care of NSCLC patients where the advantages of carboplatin over cisplatin are still appreciated.
本II期研究评估了在初治的晚期非小细胞肺癌（NSCLC）患者中，每周口服长春瑞滨联合每3周一次的卡铂（CBDCA），AUC为5，共四个周期的疗效和安全性，随后对病情无进展的患者采用单药口服长春瑞滨进行巩固治疗。
初治的晚期NSCLC患者接受四个周期的联合治疗，第1天给予CBDCA，AUC为5，同时在第1、8和15天口服长春瑞滨，60mg/m²（第1周期），若未出现3-4级中性粒细胞减少（NCI-CTCv2），则在第2-4周期将剂量增至80mg/m²。病情无进展的患者继续采用相同剂量的口服长春瑞滨进行巩固治疗（第5周期）；若在联合治疗期间剂量降低，则给予60mg/m²，然后在未出现3-4级中性粒细胞减少的情况下增至80mg/m²（第6周期），直至疾病进展、出现毒性反应或患者拒绝治疗。
共登记57例患者，56例患者接受治疗（意向性分析人群），中位年龄为61岁（37-71岁）。根据RECIST评估的客观缓解率为17.9%（95%置信区间，CI [8.9-30.4]），疾病控制率（完全缓解、部分缓解、疾病稳定）为73.2%（95%CI [59.7-84.2]），中位无进展生存期为4.3个月（95%CI [3.1-5.1]），中位总生存期为9.7个月（95%CI [7.7-1,1.9]），1年生存率为37.1%（95%CI [24.4, 49.9]）。67.9%的患者在联合治疗期间出现3-4级中性粒细胞减少，20%的患者在巩固治疗期间出现；4例患者（7.1%）在联合治疗期间出现发热性中性粒细胞减少。非血液学毒性主要发生在联合治疗期间（7.1%的患者出现3级恶心和3级呕吐）。
每3周为一周期，每周口服长春瑞滨联合卡铂，随后采用单药口服长春瑞滨进行巩固治疗，在缓解率和生存率方面能够取得与包括卡铂在内的其他双联方案相当的疗效。该方案在晚期NSCLC治疗中显示出良好的耐受性，使得在仍重视卡铂相对于顺铂优势的NSCLC患者姑息治疗中，可轻松推荐使用该联合方案。
