Brandes A A, Rigon A, Zampieri P, Scelzi E, Amistà P, Berti F, Rotilio A, Gardiman M, Fiorentino M V
Department of Medical Oncology, University of Padova, Italy.
J Neurooncol. 1996 Dec;30(3):247-55. doi: 10.1007/BF00177276.
The poor results from treatment of high grade glioma prompted us to explore new protocols involving concurrent radio-chemotherapy. Our primary objective was to evaluate the feasibility of very early postoperative chemotherapy with BCNU, concurrent radio-chemotherapy with carboplatin and teniposide, and post-radiotherapy BCNU. Our secondary objectives were to evaluate time to progression, and overall survival.
We treated 24 newly diagnosed patients (pts) with BCNU 150 mg/m2 seven days after surgery. Thirty days later, we started radiotherapy, 1.8 to 2 Gy/day for 5 days a week on limited fields up to 60 Gy, and concurrent chemotherapy with carboplatin 250 mg/m2 on days 1, 22, and 43, and teniposide 50 mg/m2 on days 1, 2, 3, 22, 23, 24, 43, 44 and 45. Two cycles of 150 mg/m2 BCNU were then given at 30 and 70 days, respectively, after the end of the radio-chemotherapy course. Therapy was then suspended, but if disease progression was evident, treatment was resumed with drugs that had not been previously employed. Surgical reintervention was not routinely considered.
Following radio-chemotherapy treatment in the 24 pts evaluable for response, we observed partial remissions in 8 cases (33%) and stable disease in 12 (50%). Actuarial estimates of progression free survival (PFS) were 33 weeks, with 56 wks for anaplastic astrocytoma and 31 weeks for glioblastoma. Median survival time (MST) of all pts was 58 weeks; 51 weeks for glioblastoma and was not reached for anaplastic astrocytoma. This regimen was feasible. Of 144 planned cycles, 139 were delivered, and among these only in 13 and 9 cycles the doses were reduced by 75 and 50%, respectively. We did not observe any gastrointestinal toxicity. Grade 2 hematological toxicity occurred in 25% of pts. grade 3 in 4% and neurological toxicity in 3% of the pts during BCNU delivery, probably due to a sharp increase in intracranial pressure.
Early chemotherapy, concurrent chemo-radiotherapy and brief post-radio-therapy chemotherapy are feasible and well tolerated. The objective response and disease stabilization rates appear similar to previous experiences.
高级别胶质瘤的治疗效果不佳促使我们探索新的联合放化疗方案。我们的主要目标是评估术后极早期使用卡莫司汀（BCNU）化疗、卡铂和替尼泊苷同步放化疗以及放疗后使用BCNU的可行性。次要目标是评估疾病进展时间和总生存期。
我们对24例新诊断患者在术后7天给予150mg/m²的BCNU治疗。30天后，开始放疗，每周5天，每天1.8至2Gy，在有限野照射直至60Gy，并在第1、22和43天同步给予250mg/m²的卡铂化疗，在第1、2、3、22、23、24、43、44和45天给予50mg/m²的替尼泊苷化疗。在放化疗疗程结束后，分别于第30天和第70天给予两个周期的150mg/m²的BCNU。然后暂停治疗，但如果疾病进展明显，则使用之前未用过的药物恢复治疗。一般不考虑手术再次干预。
在可评估反应的24例患者接受放化疗后，我们观察到8例（33%）部分缓解，12例（50%）疾病稳定。无进展生存期（PFS）的精算估计为33周，间变性星形细胞瘤为56周，胶质母细胞瘤为31周。所有患者的中位生存期（MST）为58周；胶质母细胞瘤为51周，间变性星形细胞瘤未达到。该方案是可行的。在计划的144个周期中，实施了139个周期，其中仅在13个和9个周期中剂量分别减少了75%和50%。我们未观察到任何胃肠道毒性。25%的患者出现2级血液学毒性。在给予BCNU期间，4%的患者出现3级毒性，3%的患者出现神经毒性，可能是由于颅内压急剧升高所致。
早期化疗、同步放化疗和简短的放疗后化疗是可行的，且耐受性良好。客观缓解率和疾病稳定率似乎与以往经验相似。
