术后卡铂、依托泊苷和大剂量甲氨蝶呤在儿童中枢神经系统胚胎性肿瘤中的活性：一项针对新诊断儿童的II期研究结果

Activity of postoperative carboplatin, etoposide, and high-dose methotrexate in pediatric CNS embryonal tumors: results of a phase II study in newly diagnosed children.

作者信息

Kellie Stewart J, Wong Christopher K F, Pozza Luciano Dalla, Waters Keith D, Lockwood Liane, Mauger David C, White Les

机构信息

Oncology Unit, The Children's Hospital at Westmead and The University of Sydney, NSW, Australia.

出版信息

Med Pediatr Oncol. 2002 Sep;39(3):168-74. doi: 10.1002/mpo.10137.

DOI:10.1002/mpo.10137

PMID:12210445

Abstract

BACKGROUND

Chemotherapy is used as an alternative to irradiation or to minimize the irradiation exposure among infants with medulloblastoma or other CNS embryonal tumors. Adjuvant chemotherapy is commonly used in older children with high-risk medulloblastoma to improve survival or to allow a reduction in the craniospinal irradiation dose in standard-risk patients. However, optimal multimodality therapy, including the precise role of chemotherapy, has not been defined for these groups of patients. The objective of the present study is to assess the efficacy and toxicity of four postoperative courses of carboplatin, etoposide, and high-dose methotrexate in newly diagnosed children with medulloblastoma or other CNS embryonal tumors.

PROCEDURE

Twenty-eight children, aged from 0.3 to 15.9 years (median, 6.2 years) with post-operative measurable residual CNS embryonal tumors were enrolled, comprising medulloblastoma (n = 19), supratentorial PNET (n = 7), and pineoblastoma (n = 2). Post-operative chemotherapy comprised carboplatin 350 mg/m(2) and etoposide 100 mg/m(2) on Days 1 & 2, and methotrexate 8 g/m(2) on Day 3, repeated at 21-28-day intervals for a total of four courses. Therapy following completion of the initial Phase II study was influenced by patient age and investigator preference.

RESULTS

The combined complete response rate (CR, 7/19) and partial response rate (PR, 7/19) was 74% in patients with medulloblastoma, 89% for patients with PNET/pineoblastoma (CR, 2/9 and PR, 6/9), and for all patients it was 79%. Patients aged < 3 years at diagnosis had a combined PR and CR rate of 71% compared to 81% in patients aged > 3 years. Treatment was well tolerated although myelosuppression and thrombocytopenia were common.

CONCLUSIONS

The combination of carboplatin, etoposide, and high-dose methotrexate is highly active in pediatric patients with CNS embryonal tumors.

摘要

背景

化疗被用作放疗的替代方法，或用于尽量减少髓母细胞瘤或其他中枢神经系统胚胎性肿瘤患儿的放疗暴露。辅助化疗常用于高危髓母细胞瘤的大龄儿童，以提高生存率，或使标准风险患者的全脑脊髓照射剂量得以降低。然而，尚未明确针对这些患者群体的最佳多模式治疗方案，包括化疗的确切作用。本研究的目的是评估卡铂、依托泊苷和大剂量甲氨蝶呤四个术后疗程对新诊断的髓母细胞瘤或其他中枢神经系统胚胎性肿瘤患儿的疗效和毒性。

程序

纳入28例年龄在0.3至15.9岁（中位年龄6.2岁）、术后有可测量的残留中枢神经系统胚胎性肿瘤的患儿，包括髓母细胞瘤（n = 19）、幕上原始神经外胚层肿瘤（n = 7）和松果体母细胞瘤（n = 2）。术后化疗包括第1天和第2天给予卡铂350 mg/m²和依托泊苷100 mg/m²，第3天给予甲氨蝶呤8 g/m²，每21 - 28天重复一次，共四个疗程。初始II期研究完成后的治疗受患者年龄和研究者偏好的影响。

结果

髓母细胞瘤患者的完全缓解率（CR，7/19）和部分缓解率（PR，7/19）之和为74%，原始神经外胚层肿瘤/松果体母细胞瘤患者为89%（CR，2/9和PR，6/9），所有患者为79%。诊断时年龄<3岁的患者PR和CR率之和为71%，而年龄>3岁的患者为81%。尽管骨髓抑制和血小板减少很常见，但治疗耐受性良好。