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Fractionated Cyclophosphamide and Etoposide for Children With Advanced or Refractory Solid Tumors: A Phase II Window Study

From the Department of Pediatrics, Division of Hematology/Oncology, and Department of Pharmacology, University of Texas Southwestern Medical Center at Dallas, Dallas, TX.

Address reprint requests to Barton A. Kamen, MD, PhD, Departments of Pediatrics and Pharmacology, Cancer Institute of New Jersey, 195 Little Albany St, PO Box 2681, New Brunswick, NJ 08903-2681; email kamenba{at}umdnj.edu

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.

B.A.K. is an American Cancer Society Clinical Research Professor.

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