A study of sequential high dose cyclophosphamide and high dose carboplatin with peripheral stem-cell rescue in resistant or recurrent pediatric brain tumors

• Published in: Journal of neuro-oncology 2005, Vol.71 (2), p.181-187
• Main Authors: FOREMAN, N. K, SCHISSEL, D, LE, Tuan, STRAIN, J, FLEITZ, J, QUINONES, R, GILLER, R
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Antineoplastic Agents - administration & dosage; Antineoplastic Agents - therapeutic use; Antineoplastic Agents, Alkylating - administration & dosage; Antineoplastic Agents, Alkylating - therapeutic use; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Biological and medical sciences; Brain Neoplasms - therapy; Carboplatin - administration & dosage; Carboplatin - therapeutic use; Child; Child, Preschool; Cyclophosphamide - administration & dosage; Cyclophosphamide - therapeutic use; Development. Senescence. Regeneration. Transplantation; Dose-Response Relationship, Drug; Drug Resistance, Neoplasm; Female; Fundamental and applied biological sciences. Psychology; Hematopoietic Stem Cell Transplantation; Hormones. Endocrine system; Humans; Male; Medical sciences; Neoplasm Recurrence, Local - therapy; Neurology; Pharmacology. Drug treatments; Salvage Therapy; Vertebrates: nervous system and sense organs
• ISSN: 0167-594X; 1573-7373
• DOI: 10.1007/s11060-004-1366-2

To determine the maximum tolerated dose (MTD) of carboplatin with autologous hematopoietic stem-cell rescue, in children with poor-prognosis brain tumors. A previously determined dose of cyclophosphamide with stem-cell rescue was used as a first course. In a second course, carboplatin was given for 3 days with stem-cell rescue to 20 children. The starting dose of carboplatin was 400 mg/m2/day with increments of 75 mg/m2/day in subsequent cohorts. Toxicity and tumor response were recorded. There were two grade IV toxicities at the dose level of 775 mg/m2/day. There were no toxic deaths. Thus, the MTD of carboplatin was 700 mg/m2/day for 3 days. There were six complete responses (33%, 95% confidence interval [CI], 13-59%), two partial responses (11%; 95% CI, 1-35%), four with stable diseases (22%; 95% CI, 6-48%) and six progressed (33%; 95% CI, 13-59%) out of 18 assessable. Seven of the eight responses were in primitive neuroectodermal tumors (PNETs) or Germinomas. One child with a metastatic anaplastic astrocytoma had a CR. The median duration of tumor response was 10 months (range: 1.5-87 months) with two children disease free at 66 and 87 months. Actuarial survival is 21%. Median follow-up of survivors is 35 months (range: 15-87 months). The MTD of carboplatin with stem-cell rescue is 700 mg/m2/day for 3 days. Sequential stem-cell supported cyclophosphamide and carboplatin was tolerable in children with brain tumors and produced responses in PNETs and Germinomas.