High-dose cytosine arabinoside in the treatment of acute myelogenous leukemia: contributions to outcome of clinical and laboratory attributes.
High-dose cytosine arabinoside (HDAra-C) has been used for remission induction, and in conventional doses for maintenance in a trial of single-agent therapy in 43 previously untreated patients with acute myelogenous leukemia (AML). Rationale for the trial was provided by the observed decrease in leukemic blast cell self-renewal in culture following exposure to Ara-C. Compared with a previous trial of 57 patients treated with multidrug therapy, single-drug Ara-C was associated with a significantly improved complete remission rate (P = .010), although the survival time was not increased. All patients with low self-renewal responded to HDAra-C in contrast to the previous trial where some patients with this phenotype failed remission induction. The clinical observations are consistent with the view that the antileukemic effect of Ara-C has some specificity for cellular events required for self-renewal of blast cells. Exposure in vivo to Ara-C was associated with an increase in blast stem cell renewal at relapse, indicating that maintenance with other drugs should be tested. The study demonstrates the importance of biological attributes in design and analysis of clinical trials.
D000293:Adolescent; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D016026:Bone Marrow Transplantation; D002648:Child; D002986:Clinical Trials as Topic; D003561:Cytarabine / Q000008:administration & dosage / Q000627:therapeutic use*; D004317:Doxorubicin / Q000008:administration & dosage; D004338:Drug Combinations / Q000008:administration & dosage; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D008875:Middle Aged; D014411:Neoplastic Stem Cells / Q000145:classification; D010641:Phenotype; D012074:Remission Induction; D013223:Statistics as Topic; D013420:Sulfamethoxazole / Q000008:administration & dosage; D013866:Thioguanine / Q000008:administration & dosage; D014295:Trimethoprim / Q000008:administration & dosage; D015662:Trimethoprim, Sulfamethoxazole Drug Combination; D014410:Tumor Stem Cell Assay
D004338:Drug Combinations; D003561:Cytarabine; D004317:Doxorubicin; D015662:Trimethoprim, Sulfamethoxazole Drug Combination; D014295:Trimethoprim; D013866:Thioguanine; D013420:Sulfamethoxazole