Mirimanoff R O, Moro D, Bolla M, Michel G, Brambilla C, Mermillod B, Miralbell R, Alberto P
Department of Radiation Oncology, University of Lausanne (CHUV), Switzerland.
Int J Radiat Oncol Biol Phys. 1998 Oct 1;42(3):487-94. doi: 10.1016/s0360-3016(98)00246-6.
PURPOSE/OBJECTIVE: To report on two consecutive Phase II cooperative trials in which we evaluated the combination of alternating hyperfractionated accelerated radiotherapy and cisplatin-based chemotherapy in inoperable Stage III non-small cell lung cancer (NSCLC).
PATIENTS & METHODS: Between February 1986 and September 1989, 65 patients were entered in the first trial (GOTHA I), and between December 1989 and October 1992 67 were enrolled in the second trial (GOTHA II). In both protocols, radiotherapy (RT) was administered twice daily, at 6 h intervals, 5 days a week, to a total dose of 63 Gy in 42 fractions of 1.5 Gy. RT was given during weeks 2, 3, 6, and 7, over an elapsed time of 6 weeks. In GOTHA I, three cycles of cisplatin, 60 mg/m2 day 1, mitomycin, 8 mg/m2 day 1, and vindesin 3 mg/m2 day 1 and the first day of the following week, were given during weeks 1, 5, and 9; in GOTHA II, cisplatin 70 mg/m2 day 1 and vinblastin 5 mg/m2 day 1 and the first day of the following week were given during weeks 1, 5, 9, 13, 17, and 21.
With a minimum follow-up of 3 years, the 1-, 2-, 5-, and 8-year overall survival probability was 56% (95% CI 47-64%), 27% (20-35%), 12% (7-18%) and 9% (3-16%), respectively, with a median survival of 13.6 months (11.4-16.8). Median follow-up for survivors was 6 years (3.3-9.9). There were no survival differences between Stages IIIA and IIIB (p = 0.84), performance status 0, 1, 2 (p = 0.87), sex (p = 0.45) or between the two treatment protocols. At this time, 14 patients are alive, and 118 have died: 102 from NSCLC, 4 from acute toxicity, 2 from secondary surgery, 4 from other medical causes, and 6 from unknown causes. Correlation between response and long-term survival was poor, since of the 24 patients who survived 3 years or more, only 6 (25%) were classified as having a complete response; the remainder having either a partial response (11, 46%), no change (6, 25 %), or "progressive disease" (1, 4 %). First site of relapse was local in 31% of these cases, distant in 43%, local and distant in 15 %, and unknown in 11%. Main grade 3-4 acute toxicities were nausea-vomiting (17%), mucositis (15%), leukopenia (41%), and thrombocytopenia (11%). Eight patients presented with grade 3-4 symptomatic lung radiation pneumopathy.
Based on this experience with 132 patients, this combination of alternated RT and chemotherapy (CT) for inoperable Stage III NSCLC is feasible with acceptable toxicity, and long-term results suggest a gain in survival when compared to those obtained with conventional RT alone. However, the still high local and distant failure rates indicate that both local and systemic therapies need to be improved.
目的/目标：报告两项连续的II期合作试验，在试验中我们评估了交替超分割加速放疗和顺铂为基础的化疗联合应用于不可切除的III期非小细胞肺癌（NSCLC）的疗效。
在1986年2月至1989年9月期间，65例患者进入第一项试验（GOTHA I），在1989年12月至1992年10月期间，67例患者进入第二项试验（GOTHA II）。在两项方案中，放疗（RT）每天进行两次，间隔6小时，每周5天，总剂量63 Gy，分42次，每次1.5 Gy。放疗在第2、3、6和7周进行，历时6周。在GOTHA I中，在第1、5和9周给予三个周期的顺铂，60 mg/m²第1天，丝裂霉素，8 mg/m²第1天，长春地辛3 mg/m²第1天以及下周的第一天；在GOTHA II中，在第1、5、9、13、17和21周给予顺铂70 mg/m²第1天，长春花碱5 mg/m²第1天以及下周的第一天。
最小随访3年，1年、2年、5年和8年的总生存概率分别为56%（95% CI 47 - 64%），27%（20 - 35%），12%（7 - 18%）和9%（3 - 16%），中位生存期为13.6个月（11.4 - 16.8）。幸存者的中位随访时间为6年（3.3 - 9.9）。IIIA期和IIIB期之间、体能状态0、1、2级之间（p = 0.87）、性别（p = 0.45）或两种治疗方案之间的生存无差异。此时，14例患者存活，118例死亡：102例死于NSCLC，4例死于急性毒性，2例死于二次手术，4例死于其他医疗原因，6例死因不明。缓解与长期生存之间的相关性较差，因为在24例存活3年或更长时间的患者中，只有6例（25%）被分类为完全缓解；其余患者有部分缓解（11例，46%）、病情无变化（6例，25%）或“疾病进展”（1例，4%）。这些病例中31%的首次复发部位为局部，43%为远处，15%为局部和远处，11%不明。主要的3 - 4级急性毒性反应为恶心呕吐（17%）、黏膜炎（15%）、白细胞减少（41%）和血小板减少（11%）。8例患者出现3 - 4级有症状的放射性肺炎。
基于对132例患者的经验，这种交替放疗和化疗（CT）联合应用于不可切除的III期NSCLC是可行的，毒性可接受，长期结果表明与单独使用传统放疗相比生存期有所延长。然而，局部和远处失败率仍然较高，表明局部和全身治疗都需要改进。
