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/m(2)/ day, x 4 days; thiotepa 300 mg/m(2)/ day, x 3 days; and carboplatin similar to 500 mg/ m(2)/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.