High-dose cyclophosphamide-irinotecan-vincristine for primary refractory neuroblastoma

Eur J Cancer. 2011 Jan;47(1):84-9. doi: 10.1016/j.ejca.2010.09.014. Epub 2010 Oct 8.

Abstract

Background: We used a novel regimen for neuroblastoma (NB) that had responded inadequately to standard chemotherapy which now includes topotecan in induction or second-line therapy.

Patients and methods: We retrospectively studied 38 patients who received one or two courses of high-dose cyclophosphamide (140 mg/kg)-irinotecan (CPT-11) (250 mg/m(2))-vincristine (HD-CCV) as treatment for NB that had responded incompletely to induction but had never progressed. Treatment was outpatient and was preceded and followed by extent-of-disease and toxicity evaluations because the patients were being considered for enrolment on formal protocols. Progression-free survival (PFS) was calculated from day 1 of HD-CCV.

Results: Common toxicities were grade 4 myelosuppression and grade 2 diarrhoea. Responses--5 complete (CR), 3 partial (PR), 4 mixed (MR)--occurred in 12/28 (43%) patients treated ≤9 months, and in 1/10 (10%) patients treated >10 months, from diagnosis. HD-CCV was the initial salvage regimen after topotecan-containing induction in 5 patients, achieving 1 CR, 1 MR and 3 stable disease (NR). HD-CCV produced responses (2 PR, 3 MR) in all 5 patients previously treated with CPT-11/ temozolomide. In contrast, all 6 patients treated post-HD-CCV with CPT-11/temozolomide had NR to the latter. Post-HD-CCV treatments included immunotherapy, targeted radiotherapy and/or chemotherapy. PFS was 64% (±8%) at 24 months, with 20 patients progression-free at 2+-to-36+ (median 16+) months and 10 in first CR at 9+-to-36+ (median 16+) months.

Conclusions: HD-CCV offers a treatment option against topotecan-resistant NB. Results support the concept that combining CPT-11 with very high doses of alkylators can yield greater antitumour effect.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Camptothecin / administration & dosage
  • Camptothecin / analogs & derivatives
  • Child
  • Child, Preschool
  • Cyclophosphamide / administration & dosage
  • Disease-Free Survival
  • Drug Resistance, Neoplasm
  • Female
  • Humans
  • Infant
  • Irinotecan
  • Male
  • Neuroblastoma / drug therapy*
  • Retrospective Studies
  • Vincristine / administration & dosage

Substances

  • Vincristine
  • Irinotecan
  • Cyclophosphamide
  • Camptothecin