High-dose therapy/stem cell support: comparison of mice and humans

International Journal of Cancer. Journal International Du Cancer
B A TeicherE Frei

Abstract

A murine high-dose therapy/stem cell support model is described using female BALB/c mice bearing the EMT-6 mammary carcinoma. Peripheral blood cells were prepared in syngeneic donor animals mobilized by treatment with cyclophosphamide and rhG-CSF. The most effective support regimen includes administration of fluid by gavage, rhG-CSF twice per day for 12 days and peripheral blood cells administered i.v. on the day after cytotoxic therapy. Dose escalations of 2.2- to 13-fold over the usual conventional dose were possible in mice treated with single doses of cyclophosphamide, carmustine, melphalan, thiotepa, carboplatin or total body radiation, which compare favorably with dose escalations achievable in humans. Depletion and recovery rates of white blood cells and granulocytes in the mice were similar to those seen in humans. Rapid weight loss is a major factor in limiting further dose escalation. Single high-dose therapy with cyclophosphamide, melphalan, thiotepa and carboplatin, but not 5-fluorouracil, produced longer tumor growth delays than standard regimens of the same drugs. For melphalan and thiotepa, there was a direct correlation between drug dose, tumor growth delay and tumor surviving fraction. With cyclophosphamide, th...Continue Reading

References

Jan 1, 1989·Cancer Chemotherapy and Pharmacology·B A TeicherT S Herman
Jan 15, 1994·International Journal of Radiation Oncology, Biology, Physics·S J KnoxR T Hoppe
Jan 1, 1993·Breast Cancer Research and Treatment·S F Williams
Jan 1, 1993·Cancer Investigation·C S Johnson

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Citations

Feb 13, 2003·Pediatric Clinics of North America·Ulrike Reiss, Ellen Bolotin
Sep 17, 1996·International Journal of Cancer. Journal International Du Cancer·B A TeicherD Northey
Oct 17, 2006·Molecular Cancer Therapeutics·Beverly A Teicher

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