Singhal Nimit, Mislang Anna, Karapetis Christos S, Stephens Sonya, Borg Martin, Woodman Richard J, Pittman Kenneth
aDepartment of Medical Oncology, University of Adelaide bDepartment of Radiation Oncology, Royal Adelaide Hospital, North Terrace Adelaide cDepartment of Medical Oncology, The Queen Elizabeth Hospital, Woodville South dFlinders Centre for Innovation in Cancer, Flinders University eFlinders Centre for Epidemiology and Biostatistics, School of Medicine, Flinders University, Bedford Park, South Australia, Australia.
Anticancer Drugs. 2015 Nov;26(10):1083-8. doi: 10.1097/CAD.0000000000000291.
Chemoradiotherapy regimens for stage III non-small-cell lung cancer (NSCLC) require ongoing evaluation. This South Australian multicentre prospective phase II study evaluated the safety, activity and outcomes of combination oral vinorelbine and cisplatin administered concurrently with radiotherapy for stage III NSCLC. Consecutive eligible patients received two cycles of oral vinorelbine 50 mg/m day 1 (D1), day 8 (D8) and intravenous cisplatin 50 mg/m D1 and D8 in a 21-day cycle. Chemotherapy was administered concurrently with radiotherapy at 60 Gy in 30 fractions, 2 Gy/fraction to the isocentre, all fields treated daily, 5 days a week over 6 weeks using 10 MV photons and three-dimensional conformal radiotherapy. The primary endpoint was to evaluate the progression-free survival (PFS). The secondary end points were safety, response rates and overall survival (OS). Forty-three eligible patients with stage III NSCLC - comprising 21 squamous cell carcinoma, 18 adenocarcinoma and four large cell carcinoma - were studied. Four patients did not complete the treatment. By intention-to-treat analysis, 25% showed a partial response and 65% had stable disease. None achieved a complete response. Of the 39 patients who completed protocol-specified treatment, 11 (28%) showed a partial response and 28 (72%) had stable disease. The median PFS was 25.2 months and the median OS was 48.3 months. Toxicities were manageable and generally mild, with the majority being either grade 1 (n=38) or grade 2 (n=21). Toxicities were mainly of oesophagitis, pneumonitis, fatigue, nausea and dysphagia. Two cycles of chemotherapy with oral vinorelbine and cisplatin administered concurrently with radical radiation had an acceptable toxicity profile and was active in inoperable stage III NSCLC. PFS and OS outcomes were encouraging. This regimen warrants further investigation.
III期非小细胞肺癌（NSCLC）的放化疗方案需要持续评估。这项南澳大利亚多中心前瞻性II期研究评估了口服长春瑞滨与顺铂联合放疗用于III期NSCLC的安全性、活性和疗效。符合条件的连续患者接受两个周期的口服长春瑞滨，剂量为50mg/m²，第1天（D1）、第8天（D8）给药，静脉注射顺铂50mg/m²，于D1和D8给药，每21天为一个周期。化疗与放疗同时进行，总剂量60Gy，分30次，每次2Gy至等中心，所有野每日照射，每周5天，共6周，使用10MV光子和三维适形放疗。主要终点是评估无进展生存期（PFS）。次要终点是安全性、缓解率和总生存期（OS）。对43例符合条件的III期NSCLC患者进行了研究，其中包括21例鳞状细胞癌、18例腺癌和4例大细胞癌。4例患者未完成治疗。意向性分析显示，25%的患者部分缓解，65%的患者病情稳定。无患者完全缓解。在完成方案规定治疗的39例患者中，11例（28%）部分缓解，28例（72%）病情稳定。中位PFS为25.2个月，中位OS为48.3个月。毒性反应可控，一般较轻，大多数为1级（n = 38）或2级（n = 21）。毒性反应主要为食管炎、肺炎、疲劳、恶心和吞咽困难。口服长春瑞滨和顺铂联合根治性放疗的两个周期化疗具有可接受的毒性特征，对无法手术的III期NSCLC有活性。PFS和OS结果令人鼓舞。该方案值得进一步研究。
