Hypoxanthine:guanine phosphoribosyltransferase activity in primary human osteosarcomas. A rationale for therapy with methotrexate-thymidine rescue?
Hypoxanthine:guanine phosphoribosyltransferase (HPRT) activity was measured in 14 human osteosarcomas to test whether a subset of these tumors was deficient in the purine salvage pathway enzyme and thus provide a rationale for therapy with methotrexate-thymidine rescue. All tumors contained HPRT activity within the range previously reported for xenografts of human osteosarcoma. Three patients received methotrexate (3.375 g/m2/24 hours) as a 72-hour continuous infusion with thymidine rescue (2.0 g/m2/24 hours) beginning 24 hours after the start of the methotrexate infusion. The methotrexate-thymidine infusion was well tolerated by all patients with no significant toxicity; however, there were no responses. We conclude that osteosarcomas are not deficient in HPRT activity. Therefore, the previously reported rationale for therapy of osteosarcoma with methotrexate-thymidine based on lack of activity of this enzyme is not valid. This combination, although well tolerated, is inconvenient and requires prolonged hospitalization. Therefore, without a valid rationale it cannot be recommended for therapy of patients with osteosarcoma.
D000971:Antineoplastic Combined Chemotherapy Protocols / Q000378:metabolism* / Q000627:therapeutic use; D001859:Bone Neoplasms / Q000556:secondary; D002648:Child; D005260:Female; D006801:Humans; D019271:Hypoxanthine; D007041:Hypoxanthine Phosphoribosyltransferase; D007042:Hypoxanthines / Q000378:metabolism*; D008175:Lung Neoplasms / Q000556:secondary; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage; D012516:Osteosarcoma / Q000188:drug therapy / Q000201:enzymology* / Q000556:secondary; D010430:Pentosyltransferases / Q000378:metabolism*; D013936:Thymidine / Q000008:administration & dosage
D007042:Hypoxanthines; D019271:Hypoxanthine; D010430:Pentosyltransferases; D007041:Hypoxanthine Phosphoribosyltransferase; D013936:Thymidine; D008727:Methotrexate