High-dose carboplatin-irinotecan-temozolomide: treatment option for neuroblastoma resistant to topotecan.
BACKGROUND
We report a retrospective study of a novel regimen for neuroblastoma (NB) resistant to standard induction or salvage chemotherapy which now routinely includes topotecan.


METHODS
Forty-five patients received carboplatin (500 mg/m(2)/day, 2×)-irinotecan (50 mg/m(2)/day, 5×)-temozolomide (250 mg/m(2)/day, 5×) (HD-CIT). Only one course was planned. Patients with thrombocytopenia indicative of poor bone marrow (BM) reserve resulting from extensive prior therapy received peripheral blood stem cells (PBSCs) post-HD-CIT.


RESULTS
Modest acute toxicity allowed outpatient treatment. Low-grade diarrhea was common; there was no mucositis, nephrotoxicity, or cardiotoxicity. Myelosuppression was prolonged but uncomplicated. The absolute neutrophil count reached 500/µl on days 20-30 (median, 25) in 25 patients with satisfactory BM reserve, and on days 9-14 (median, 11) post-PBSC infusion. Anti-NB activity was common against refractory (non-progressing) disease or new relapse occurring off therapy (68% objective response rate), but not against disease progressing on therapy. Seven of 26 patients treated for refractory NB are progression-free and in complete remission following subsequent therapy, including anti-G(D2) immunotherapy, at ≥ 29+ months post-HD-CIT.


CONCLUSIONS
HD-CIT is appealing as salvage or consolidative therapy because of anti-NB activity and modest non-hematologic toxicity. PBSC support is unnecessary when BM reserve is intact. The wide antineoplastic activity of its three components and their potential for activity against disease in the central nervous system support applicability to other cancers.
Department of Pediatrics, Memorial Sloan-Kettering Cancer Center, New York, New York 10065, USA. kushnerb@mskcc.org
Brian H
BH
Kushner
Kim
K
Kramer
Shakeel
S
Modak
Nai-Kong V
NK
Cheung
D000293:Adolescent; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives; D016190:Carboplatin / Q000008:administration & dosage; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D003606:Dacarbazine / Q000008:administration & dosage / Q000031:analogs & derivatives; D004305:Dose-Response Relationship, Drug; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D000077146:Irinotecan; D008297:Male; D009447:Neuroblastoma / Q000188:drug therapy* / Q000473:pathology; D012074:Remission Induction; D012189:Retrospective Studies; D016879:Salvage Therapy; D015996:Survival Rate; D000077204:Temozolomide; D019772:Topotecan / Q000008:administration & dosage; D016896:Treatment Outcome
D000077146:Irinotecan; D003606:Dacarbazine; D019772:Topotecan; D016190:Carboplatin; D002166:Camptothecin; D000077204:Temozolomide