Prados M D, Wara W, Edwards M S, Ater J, Rabbit J, Lamborn K, Davis R, Levin V A
Department of Neurosurgery, University of California, San Francisco, USA.
Pediatr Neurosurg. 1996 Oct;25(4):174-81. doi: 10.1159/000121120.
To investigate toxicity, and progression-free survival (PFS) of children and adults with newly diagnosed medulloblastoma, pineoblastoma, and other primitive neuroectodermal tumors (PNET) with a combined modality regimen of radiation therapy and adjuvant nitrosourea-based chemotherapy.
Between 1984 and 1992, 34 evaluable patients with newly diagnosed tumors were treated with chemotherapy and radiotherapy according to a single-arm phase II study. One cycle of chemotherapy was given prior to and for 6 cycles following craniospinal radiotherapy (CSA). Procarbazine, 6-thioguanine, and dibromodulcitol were given before lomustine (CCNU) to enhance CCNU-induced tumor cell kill and to reduce alkyltransferase repair of ethylated DNA. Vincristine was given 1 and 3 weeks after CCNU to kill cells that began to cycle after the challenge of the first four drugs. Chemotherapy was given in the outpatient setting. CSA radiation was planned to deliver a dose of 54 Gy to the primary tumor site and 24 Gy to the rest of the neuroaxis. Additional radiation was given to bulky disease outside the primary site if present. Hydroxyurea was used during radiotherapy as a radiosensitizer.
Patients treated included 27 with medulloblastoma, 5 with pineoblastoma, and 2 with supratentorial PNET. All but 3 medulloblastoma cases were considered high risk either because of bulky residual disease remaining after surgery and/or metastatic disease detected during staging. For the 34 patients, 24 have progressed, 20 have died. Overall estimated PFS was 55% at 3 years and 35% at 5 years. The 5-year survival estimate is 56%. One patient had inadequate staging to determine M stage. Of the remaining 33 patients, there were 19 patients who had metastatic disease at diagnosis (M1 or higher stage) who had a 3- and 5-year PFS of 42 and 21% respectively and 5-year survival of 42%. There were 14 patients who had negative staging (M0 stage) who had a 3- and 5-year PFS of 69 and 52% respectively and 5-year survival of 71%. Of the 27 patients with medulloblastoma, 15 had M1 or higher stage. These 15 patients had a 5-year PFS and overall survival of only 20 and 40% respectively. Medulloblastoma patients with M0 staging had a 5-year PFS and overall survival of 52 and 73% respectively. Overall toxicity was primarily due to mild hematological toxicity and related to the use of the chemotherapy.
The results using this therapy in high-risk groups of patients does not offer any improvement over results reported in other recent studies. The reason for these results may be due to the lowered craniospinal radiation dose.
采用放疗联合亚硝基脲类辅助化疗的综合治疗方案，研究新诊断的髓母细胞瘤、松果体母细胞瘤和其他原始神经外胚层肿瘤（PNET）患儿及成人的毒性反应和无进展生存期（PFS）。
1984年至1992年间，根据一项单臂II期研究，对34例新诊断肿瘤的可评估患者进行了化疗和放疗。在全脑全脊髓放疗（CSA）之前及之后进行6个周期的化疗。在洛莫司汀（CCNU）之前给予丙卡巴肼、6-硫鸟嘌呤和二溴卫矛醇，以增强CCNU诱导的肿瘤细胞杀伤作用，并减少乙基化DNA的烷基转移酶修复。在CCNU给药后1周和3周给予长春新碱，以杀死在前四种药物作用后开始进入细胞周期的细胞。化疗在门诊进行。CSA放疗计划给予原发肿瘤部位54 Gy的剂量，神经轴其余部位24 Gy的剂量。如果存在原发部位以外的大块病灶，则给予额外放疗。放疗期间使用羟基脲作为放射增敏剂。
治疗的患者包括27例髓母细胞瘤、5例松果体母细胞瘤和2例幕上PNET。除3例髓母细胞瘤病例外，所有病例均被认为是高危病例，原因是手术后残留大块病灶和/或分期时检测到转移病灶。34例患者中，24例病情进展，20例死亡。3年时总体估计无进展生存率为55%，5年时为35%。5年生存率估计为56%。1例患者分期不足，无法确定M分期。其余33例患者中，19例在诊断时患有转移疾病（M1或更高分期），其3年和5年无进展生存率分别为42%和21%，5年生存率为42%。14例分期为阴性（M0期）的患者，其3年和5年无进展生存率分别为69%和52%，5年生存率为71%。27例髓母细胞瘤患者中，15例为M1或更高分期。这15例患者的5年无进展生存率和总生存率分别仅为20%和40%。M0分期的髓母细胞瘤患者5年无进展生存率和总生存率分别为52%和73%。总体毒性主要是由于轻度血液学毒性，与化疗的使用有关。
在高危患者组中使用这种治疗方法的结果与其他近期研究报告的结果相比没有任何改善。这些结果的原因可能是全脑全脊髓放疗剂量降低。
