J Clin Oncol. 2001 Jan 15;19(2):509-18. doi: 10.1200/JCO.2001.19.2.509.
Meta-analyses of the published literature suggest a survival benefit to adjuvant chemotherapy for high-grade astrocytoma, which individual small trials have been unable to demonstrate reliably. The Medical Research Council Brain Tumour Working Party initiated the largest randomized trial of adjuvant chemotherapy for glioma in an attempt to provide a definitive answer.
After surgery, patients aged < or = 70 years, with World Health Organization grade 3 or 4 astrocytoma, were randomized to radiotherapy alone (RT) or RT plus procarbazine, lomustine, and vincristine (PCV) chemotherapy (RT-PCV) given at 6-week intervals to a maximum of 12 courses (procarbazine 100 mg/m2 days 1 to 10, lomustine 100 mg/m2 day 1, and vincristine 1.5 mg/m2 (max 2 mg) day 1). A neuropathology panel independently reviewed all cases. To reliably detect a 10% increase in 2-year survival (from 15% to 25%), 600 patients were required.
Between September 1988 and May 1997, 15 United Kingdom centers randomized 674 patients (RT = 339 patients; RT-PCV = 335 patients). With a median follow-up for survivors of 3 years, 617 patients have died, (RT = 310 patients; RT-PCV = 307 patients). Median survival was 9.5 months for RT and 10 months for RT-PCV (hazard ratio = 0.95; 95% confidence interval, 0.81 to 1.11; log-rank P = .50). Tests for interaction revealed no significant differences in treatment effect according to tumor grade, age, performance status, or extent of neurosurgery.
This trial shows no benefit to PCV chemotherapy, and current data exclude an increase in median survival of more than 10 weeks and in a 1- or 2-year survival rate of more than 7% to 8%. This suggests that no-chemotherapy control arms remain ethical in randomized trials in high-grade astrocytoma.
对已发表文献的荟萃分析表明，辅助化疗对高级别星形细胞瘤有生存获益，而个别小型试验未能可靠地证明这一点。医学研究理事会脑肿瘤工作组开展了最大规模的胶质瘤辅助化疗随机试验，试图给出一个明确的答案。
术后，年龄≤70岁、患有世界卫生组织3级或4级星形细胞瘤的患者被随机分为单纯放疗（RT）组或放疗加丙卡巴肼、洛莫司汀和长春新碱（PCV）化疗组（RT-PCV），每6周进行一次化疗，最多12个疗程（丙卡巴肼100mg/m²，第1至10天；洛莫司汀100mg/m²，第1天；长春新碱1.5mg/m²（最大2mg），第1天）。一个神经病理学小组独立审查了所有病例。为了可靠地检测2年生存率提高10%（从15%提高到25%），需要600名患者。
1988年9月至1997年5月期间，英国的15个中心将674名患者进行了随机分组（RT组339例患者；RT-PCV组335例患者）。幸存者的中位随访时间为3年，617名患者死亡（RT组310例患者；RT-PCV组307例患者）。RT组的中位生存期为9.5个月，RT-PCV组为10个月（风险比=0.95；95%置信区间，0.81至1.11；对数秩检验P=0.50）。交互作用检验显示，根据肿瘤分级、年龄、体能状态或神经外科手术范围，治疗效果无显著差异。
该试验表明PCV化疗无获益，目前的数据排除了中位生存期增加超过10周以及1年或2年生存率增加超过7%至8%的情况。这表明在高级别星形细胞瘤的随机试验中，无化疗对照组仍然符合伦理。
