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

Authors: Kushner, B. H.; Kramer, K.; Modak, S.; Yataghene, K.; Cheung, N. K. V.
Article Title: High-dose cyclophosphamide-irinotecan-vincristine for primary refractory neuroblastoma
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/m2)- 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. © 2010 Elsevier Ltd. All rights reserved.
Keywords: child; clinical article; human tissue; preschool child; school child; treatment response; primary tumor; histopathology; cisplatin; doxorubicin; cancer combination chemotherapy; cancer growth; diarrhea; dose response; cancer radiotherapy; temozolomide; topotecan; drug megadose; cancer immunotherapy; progression free survival; infection; multiple cycle treatment; bone marrow suppression; mucosa inflammation; cyclophosphamide; vincristine; irinotecan; neuroblastoma; (3 iodobenzyl)guanidine i 131; novel regimen
Journal Title: European Journal of Cancer
Volume: 47
Issue: 1
ISSN: 0959-8049
Publisher: Elsevier Inc.  
Date Published: 2011-01-01
Start Page: 84
End Page: 89
Language: English
DOI: 10.1016/j.ejca.2010.09.014
PROVIDER: scopus
PUBMED: 20934323
Notes: --- - "Export Date: 4 March 2011" - "CODEN: EJCAE" - "Source: Scopus"
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MSK Authors
  1. Brian Kushner
    190 Kushner
  2. Nai-Kong Cheung
    439 Cheung
  3. Kim Kramer
    168 Kramer
  4. Shakeel Modak
    159 Modak