Rajkumar S V, Buckner J C, Schomberg P J, Pitot H C, Ingle J N, Cascino T L
Division of Medical Oncology, Mayo Clinic and Foundation, Rochester, Minnesota 55905, USA.
Neurosurgery. 1999 Jan;44(1):67-73. doi: 10.1097/00006123-199901000-00036.
A Phase I study was conducted to determine the safety, toxicity, and maximum tolerated dose of preirradiation chemotherapy using carmustine (BCNU) and cisplatin in the treatment of high-grade gliomas.
Patients with newly diagnosed high-grade gliomas received BCNU and cisplatin after surgery, both before and during definitive radiation therapy. Preirradiation chemotherapy consisted of an administration of 40 mg/m2 BCNU on Days 1 through 3 and 30 mg/m2 cisplatin on Days 1 through 3 and 29 through 31 and repeated at 8 weeks to coincide with the start of radiation therapy. Postradiation chemotherapy consisted of an administration of 200 mg/m2 BCNU once every 8 weeks for four cycles. Radiation therapy consisted of 160-cGy fractions administered twice daily for 15 days, yielding a total dose of 4800 cGy. Dose escalation of BCNU was planned. If hematological toxicity was mild, the dose of cisplatin was to be held constant and BCNU dose escalated to 50 mg/m2 on Days 1 through 3.
Eighteen patients were studied. The hematological toxicity was dose-limiting. Grade 3 or 4 leukopenia occurred in each of 10 patients (56%), and Grade 3 or 4 thrombocytopenia occurred in each of 9 patients (50%). Other toxicities included anorexia (94%), nausea (83%), emesis (33%), alopecia (94%), mild ototoxicity (50%), and, in one patient, death as a result of BCNU pulmonary toxicity. The median survival time was 14 months. Objective responses occurred in 45% of the patients evaluable for response. The maximum tolerated dose of this combination was 50 mg/m2 BCNU on Days 1 through 3 and 30 mg/m2 cisplatin on Days 1 through 3 and 29 through 31 before radiation and repeated in 8 weeks to coincide with the start of radiation.
This schedule of the preirradiation administration of BCNU and cisplatin with accelerated hyper-fractionated radiation therapy for the treatment of high-grade gliomas provides a less toxic alternative to that of previous studies of preirradiation chemotherapy with these agents and merits further investigation.
开展一项I期研究，以确定使用卡莫司汀（BCNU）和顺铂进行放疗前化疗治疗高级别胶质瘤的安全性、毒性及最大耐受剂量。
新诊断的高级别胶质瘤患者在手术后、确定性放疗前及放疗期间接受BCNU和顺铂治疗。放疗前化疗包括在第1至3天给予40mg/m²的BCNU，在第1至3天和第29至31天给予30mg/m²的顺铂，并在8周后重复，与放疗开始时间一致。放疗后化疗包括每8周给予一次200mg/m²的BCNU，共四个周期。放疗包括每天两次给予160cGy的分次剂量，持续15天，总剂量为4800cGy。计划对BCNU进行剂量递增。如果血液学毒性较轻，则顺铂剂量保持不变，BCNU剂量在第1至3天递增至50mg/m²。
研究了18名患者。血液学毒性为剂量限制性毒性。10名患者（56%）均出现3级或4级白细胞减少，9名患者（50%）均出现3级或4级血小板减少。其他毒性包括厌食（94%）、恶心（83%）、呕吐（33%）、脱发（94%）、轻度耳毒性（50%），且有1名患者因BCNU肺部毒性死亡。中位生存时间为14个月。45%可评估反应的患者出现客观反应。该联合方案的最大耐受剂量为放疗前第1至3天给予50mg/m²的BCNU，第1至3天和第29至31天给予30mg/m²的顺铂，并在8周后重复，与放疗开始时间一致。
这种BCNU和顺铂放疗前给药联合加速超分割放疗治疗高级别胶质瘤的方案，相比于以往这些药物放疗前化疗的研究，毒性更低，值得进一步研究。
