Baldini E, Silvano G, Tibaldi C, Campoccia S, Cionini L, Conte P
Dipartimento di Oncologia, Unita Operativa di Oncologia Medica, Pisa, Italy.
Semin Oncol. 2000 Feb;27(1 Suppl 1):28-32.
Meta-analysis has demonstrated survival benefit for patients with stage IIIB non-small cell lung cancer treated with sequential chemoradiotherapy versus radiotherapy alone. The introduction of chemotherapy as part of a multimodality approach has improved the outcome in this poor prognostic subset of cancer patients. In the present phase II study we evaluated the safety and activity of a new cisplatin-based three-drug regimen consisting of vinorelbine/ifosfamide/cisplatin (VIP) followed by curative thoracic irradiation in 28 patients with stage IIIB non-small cell lung cancer. Patients received vinorelbine 25 mg/m2 on days 1 and 8, ifosfamide 3 g/m2 on day 1 (with mesna), and cisplatin 80 mg/m2 on day 1 every 3 weeks. After three courses of induction chemotherapy, patients with objective response or stable disease were eligible for thoracic radiotherapy. Twenty-six of the 28 patients received at least three courses of chemotherapy and were evaluable for response. The response rate to induction VIP was 58% (15 of 26 patients; one complete response and 14 partial responses). Seven patients had disease stabilization and four progressed during chemotherapy. Radiation treatment started from 4 to 6 weeks after the end of chemotherapy with standard fractionation (200 cGy/day, 5 fractions/wk/6 wk). Eighteen of 22 patients started thoracic irradiation; 14 completed the treatment plan, reaching the total dose of 60 Gy. The most relevant acute and late toxicities of radiotherapy were grade 3 dysphagia and pneumonitis in two patients and grade 3 lung fibrosis in six patients. By comparing the tumor volumes before and after radiation treatment we observed six clinical remissions, three stable diseases, and five local progressions. The first site of recurrence was local in 10 of 18 patients (56%), distant in seven patients (38.8%), and both local and distant in one patient. Median progression-free survival and overall survival for the patients treated with radiotherapy (18 patients) were 14 months (range, 4 to 36 months) and 26 months (range, 7 to 54+ months), respectively; the 1- and 2-year survival rates were 61% and 52%. Curative thoracic radiotherapy was well tolerated after VIP induction chemotherapy; it reduced residual tumor volume in six patients.
荟萃分析表明，与单纯放疗相比，序贯放化疗可使IIIB期非小细胞肺癌患者受益于生存。作为多模式治疗方法的一部分引入化疗，改善了这类预后较差的癌症患者的治疗结果。在本II期研究中，我们评估了一种新的基于顺铂的三药方案（长春瑞滨/异环磷酰胺/顺铂，即VIP方案）的安全性和活性，该方案随后对28例IIIB期非小细胞肺癌患者进行根治性胸部放疗。患者在第1天和第8天接受长春瑞滨25mg/m²，在第1天接受异环磷酰胺3g/m²（同时使用美司钠），每3周在第1天接受顺铂80mg/m²。在三个疗程的诱导化疗后，客观缓解或疾病稳定的患者有资格接受胸部放疗。28例患者中有26例接受了至少三个疗程的化疗，并可评估疗效。诱导化疗VIP方案的缓解率为58%（26例患者中的15例；1例完全缓解，14例部分缓解）。7例患者疾病稳定，4例在化疗期间病情进展。放疗在化疗结束后4至6周开始，采用标准分割（200cGy/天，每周5次，共6周）。22例患者中有18例开始胸部放疗；14例完成了治疗计划，总剂量达到60Gy。放疗最相关的急性和晚期毒性反应为2例患者出现3级吞咽困难和肺炎，6例患者出现3级肺纤维化。通过比较放疗前后的肿瘤体积，我们观察到6例临床缓解、3例疾病稳定和5例局部进展。18例患者中有10例（56%）复发的首发部位为局部，7例（38.8%）为远处，1例为局部和远处均有复发。接受放疗的患者（18例）的无进展生存期和总生存期的中位数分别为14个月（范围4至36个月）和26个月（范围7至54+个月）；1年和2年生存率分别为61%和52%。在VIP诱导化疗后，根治性胸部放疗耐受性良好；它使6例患者的残留肿瘤体积减小。
