Fractionated cyclophosphamide and etoposide for children with advanced or refractory solid tumors: A phase II window study

Elpis Mantadakis, Larry Herrera, Patrick J. Leavey, Robert O. Bash, Naomi J. Winick, Barton A. Kamen

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

Purpose: Cyclophosphamide (CPA) has a broad spectrum of activity against solid tumors. Hepatic self-induction of the active metabolite 4- hydroxycyclophosphamide occurs after repeated administration. We evaluated the clinical efficacy of a window regimen that administers fractionated CPA in conjunction with etoposide (VP16) in children with advanced or refractory solid tumors. Patients and Methods: Seventeen children with advanced (n = 12) or refractory (n = 5) solid tumors were entered onto this phase II window study. The treatment regimen consisted of intravenous (IV) CPA 500 mg/m2/d and IV VP16 100 mg/m2/d. Both drugs were administered daily by short infusions for 5 consecutive days. Results: A total of 34 courses were administered, with a median of two courses per patient. The median interval between chemotherapy courses was 21 days (range, 17 to 35 days). Thirty-three courses were assessable for toxicity, and all patients were assessable for response. No life-threatening toxicities were observed. The incidence of grade 3 or 4 neutropenia was 94% and of fever and neutropenia 38%. Fever and neutropenia occurred after 12 of 26 courses without recombinant human granulocyte colony-stimulating factor (rhG-CSF) and after one of eight courses with rhG-CSF (P = .09). Grade 3 or 4 thrombocytopenia occurred after 10 courses (29%). There were no positive blood cultures. One heavily pretreated patient developed a localized perirectal abscess that required drainage. There were 10 patients (59%) with partial responses, four (23.5%) with stable disease, and three with progressive disease. Conclusion: Fractionated IV CPA and VP16 over 5 days can be safely administered in children with advanced or refractory solid tumors and has notable antineoplastic activity. (C) 2000 by American Society of Clinical Oncology.

Original languageEnglish (US)
Pages (from-to)2576-2581
Number of pages6
JournalJournal of Clinical Oncology
Volume18
Issue number13
StatePublished - Jul 2000

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Etoposide
Cyclophosphamide
Neutropenia
4-hydroxycyclophosphamide
Granulocyte Colony-Stimulating Factor
Neoplasms
Fever
Antineoplastic Agents
Abscess
Drainage
Drug Therapy
Liver
Incidence
Pharmaceutical Preparations

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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Fractionated cyclophosphamide and etoposide for children with advanced or refractory solid tumors : A phase II window study. / Mantadakis, Elpis; Herrera, Larry; Leavey, Patrick J.; Bash, Robert O.; Winick, Naomi J.; Kamen, Barton A.

In: Journal of Clinical Oncology, Vol. 18, No. 13, 07.2000, p. 2576-2581.

Research output: Contribution to journalArticle

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N2 - Purpose: Cyclophosphamide (CPA) has a broad spectrum of activity against solid tumors. Hepatic self-induction of the active metabolite 4- hydroxycyclophosphamide occurs after repeated administration. We evaluated the clinical efficacy of a window regimen that administers fractionated CPA in conjunction with etoposide (VP16) in children with advanced or refractory solid tumors. Patients and Methods: Seventeen children with advanced (n = 12) or refractory (n = 5) solid tumors were entered onto this phase II window study. The treatment regimen consisted of intravenous (IV) CPA 500 mg/m2/d and IV VP16 100 mg/m2/d. Both drugs were administered daily by short infusions for 5 consecutive days. Results: A total of 34 courses were administered, with a median of two courses per patient. The median interval between chemotherapy courses was 21 days (range, 17 to 35 days). Thirty-three courses were assessable for toxicity, and all patients were assessable for response. No life-threatening toxicities were observed. The incidence of grade 3 or 4 neutropenia was 94% and of fever and neutropenia 38%. Fever and neutropenia occurred after 12 of 26 courses without recombinant human granulocyte colony-stimulating factor (rhG-CSF) and after one of eight courses with rhG-CSF (P = .09). Grade 3 or 4 thrombocytopenia occurred after 10 courses (29%). There were no positive blood cultures. One heavily pretreated patient developed a localized perirectal abscess that required drainage. There were 10 patients (59%) with partial responses, four (23.5%) with stable disease, and three with progressive disease. Conclusion: Fractionated IV CPA and VP16 over 5 days can be safely administered in children with advanced or refractory solid tumors and has notable antineoplastic activity. (C) 2000 by American Society of Clinical Oncology.

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