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High dose cyclophosphamide with carboplatin: a tolerable regimen suitable for dose intensification in children with
S G Kreissman1, W Rackoff, M Lee
1Department of Pediatrics (Section of Hematology-Oncology), James Whitcomb Riley Hospital for Children, Indiana University School of Medicine, Indianapolis 46202, USA.
Purpose:
To determine the hematopoietic and nonhematopoietic toxicity of a novel dose-intensive chemotherapy regimen for the treatment of children with relapsed solid tumors.
Patients And Methods:
The time to hematopoietic recovery and toxicity experienced during 46 courses of high-dose cyclophosphamide (4.0 g/m2), MESNA, and carboplatin (400 mg/m2) with granulocyte colony stimulating factor (G-CSF) support in 14 children with recurrent solid tumors was reviewed.
Results:
All patients developed grade 4 neutropenia and thrombocytopenia. Recovery to an absolute neutrophil count (ANC) of 500/microliter and platelet count of 50,000/microliter occurred at a median of 15 days and 23 days respectively. Median time to ANC > 1,000/microliter and platelets > 100,000/microliter was 27 days. Hospitalization for fever and neutropenia occurred during 35 of 46 courses, with documented bacteremia in six courses. There was no grade II or greater nonhematopoietic organ toxicity. Responses (CR + PR) were observed in 6 of 11 evaluable patients.
Conclusions:
These data suggest that this regimen is tolerable in heavily pretreated children with solid tumors with myelosuppression as the primary toxicity. Due to the lack of significant nonhematopoietic toxicity, this is a good candidate regimen for dose escalation using peripheral blood progenitor cell infusions and deserves further evaluation for efficacy in children with both recurrent and newly diagnosed high-risk solid tumors.