Correlation of response to 1-beta-D-arabinofuranosyl cytosine and metabolism of drug by tumor.
Phosphorylation versus deamination of ara-C by tumor homogenates was measured in 10 patients prior to treatment with ara-C infusion. The ratio ranged from 0.24 to 1.2 in 5 malignant melanomas, 2.6 to 3.2 in 3 histiocytic lymphomas and 0.9 in a hemangiopericytoma. Treatment of the 9 patients with 2 courses of 5-day continuous ara-C infusion failed to produce objective evidence of tumor regression. The tenth patient had lymphosarcoma leukemia. The baseline ratio of ara-C phosphorylation over deamination activity of the tumor cells was 1.23. Treatment with 2 courses of continuous ara-C infusions produced a brief state of complete remission. The ratio of araC phosphorylation over deamination activity in the tumor cells after relapse was only 0.1 and retreatment with ara-C infusions failed to produce antitumor response. This study indicates that factors other than a high ratio of phosphorylation over deamination activity by the tumor seem to play an important role in the susceptibility of tumors to ara-C treatment.
D003561:Cytarabine / Q000008:administration & dosage / Q000378:metabolism / Q000627:therapeutic use*; D003597:Cytosine Nucleotides / Q000096:biosynthesis; D003641:Deamination; D005260:Female; D006393:Hemangiopericytoma / Q000188:drug therapy; D006801:Humans; D007938:Leukemia / Q000188:drug therapy; D007951:Leukemia, Myeloid / Q000188:drug therapy; D008545:Melanoma / Q000188:drug therapy; D008875:Middle Aged; D009369:Neoplasms / Q000378:metabolism*; D009360:Neoplastic Cells, Circulating / Q000378:metabolism*; D010085:Oxidative Phosphorylation; D013160:Splenic Neoplasms / Q000188:drug therapy
D003597:Cytosine Nucleotides; D003561:Cytarabine