Topotecan, thiotepa, and carboplatin for neuroblastoma: failure to prevent relapse in the central nervous system.
We report on a three-drug myeloablative regimen designed to consolidate remission and to prevent central nervous system (CNS) relapse of high-risk neuroblastoma (NB). Sixty-six NB patients received topotecan 2 mg/m2/day, x 4 days; thiotepa 300 mg/m2/day, x 3 days; and carboplatin approximately 500 mg/m2/day, x 3 days. Post-SCT treatments included radiotherapy, immunotherapy, 13-cis-retinoic acid, +/-oral etoposide. Significant nonhematologic toxicities were mucositis and skin-related in all patients, convulsions in three patients, and cardiac failure and venocclusive disease of liver in one patient each. Grade 2 hepatotoxicity led to truncating cytoreduction in two patients; both later relapsed in brain. Among 46 patients transplanted in first complete/very good partial remission (CR/VGPR), event-free survival is 54% (s.e.+/-8%) at 36 months post-SCT; notable events were three non-NB-related deaths (adenovirus on day +9, bowel necrosis at 5 months, multiorgan failure at seven months) and four relapses in brain. Of 12 patients transplanted with evidence of NB, two became long-term event-free survivors and two relapsed in the brain. Of eight patients transplanted in second or greater CR/VGPR, one became a long-term event-free survivor and seven relapsed though not in the CNS. This regimen has manageable toxicity but does not prevent CNS relapse.
Kushner
B H
BH
Department of Pediatrics, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA. kushnerb@mskcc.org
Kramer
K
K
Modak
S
S
Kernan
N A
NA
Reich
L M
LM
Danis
K
K
Cheung
N-K V
NK
D000293:Adolescent; D000970:Antineoplastic Agents / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D016190:Carboplatin / Q000008:administration & dosage / Q000009:adverse effects; D016543:Central Nervous System Neoplasms / Q000401:mortality / Q000628:therapy*; D002648:Child; D002675:Child, Preschool; D003131:Combined Modality Therapy / Q000379:methods / Q000401:mortality; D005260:Female; D006801:Humans; D008297:Male; D009364:Neoplasm Recurrence, Local / Q000401:mortality / Q000517:prevention & control*; D009447:Neuroblastoma / Q000401:mortality / Q000628:therapy*; D013852:Thiotepa / Q000008:administration & dosage / Q000009:adverse effects; D019772:Topotecan / Q000008:administration & dosage / Q000009:adverse effects; D017211:Treatment Failure
D000970:Antineoplastic Agents; D019772:Topotecan; D013852:Thiotepa; D016190:Carboplatin