mercaptopurine and ubenimex

We analyzed complete remission (CR), disease-free survival (DFS), and event-free survival (EFS) rates in two groups of patients treated with either N4-behenoyl-1-beta-D-arabinosylcytosine (BHAC) or cytarabine, and analyzed DFS with or without ubenimex, a biologic response modifier.. Newly diagnosed patients with acute myeloid leukemia (AML) were randomized to receive either BHAC or cytarabine as remission-induction combination chemotherapy and two courses of consolidation therapy. After maintenance/intensification therapy, patients in CR were randomized to receive either ubenimex and no drug.. Of 341 patients registered, 326 were assessable. The age of assessable patients ranged from 15 to 82 years (median, 48). The overall CR rate was 77%: 72% in the BHAC group and 81% in the cytarabine group, and there was a significant difference between the two groups (P = .035, chi 2 test). The predicted 55-month EFS rate of all patients was 30%: 23% in the BHAC group and 35% in the cytarabine group, with a significant difference between groups (P = .0253). The predicted 55-month DFS rate of all CR patients was 38% and that of CR patients less than 50 years of age was 47%. There was no significant difference in DFS between the ubenimex group and the group that did not receive ubenimex.. Analyses of our clinical trial showed that the use of BHAC in remission-induction therapy and in consolidation therapy resulted in poorer CR and EFS rates in adult AML patients compared with the use of cytarabine at the doses and schedules tested. Immunotherapy with ubenimex after the end of all chemotherapy did not improve DFS.

Topics: Acute Disease; Adolescent; Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Chi-Square Distribution; Cytarabine; Daunorubicin; Disease-Free Survival; Female; Follow-Up Studies; Humans; Leucine; Leukemia, Myeloid; Logistic Models; Male; Mercaptopurine; Middle Aged; Multivariate Analysis; Prednisolone; Prospective Studies; Remission Induction; Survival Rate; Treatment Outcome

We have recently performed a prognostic investigation of a randomized controlled trial with bestatin for acute non-lymphocytic leukemia in adults. Out of 115 patients registered in this study, 101 patients (48 in a bestatin group and 53 in a control group) were evaluated as eligible. The 50% remission duration was 20.4 months for the bestatin group compared with 11.3 months for the control group. Long-term remission rate at 4 years was 36.5% for the bestatin group compared with 24.1% for the control group, and their respective 50% survival time were 33.0 and 18.1 months, while the long-term survival rate at 4 years was 46.0% for the bestatin group compared with 25.5% for the control group. The bestatin group had a longer remission duration and survival time than the control group. The remission duration and survival time in patients under 49 years of age were not different between the groups. However, in patients over 50 years of age, the bestatin group had a significantly longer remission duration and survival time than the control group. Side effects of bestatin were mild and transient. These data suggest the usefulness of bestatin for the treatment of adult acute nonlymphocytic leukemia.

Topics: Aclarubicin; Acute Disease; Adjuvants, Immunologic; Adolescent; Adult; Antibiotics, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Cytarabine; Daunorubicin; Follow-Up Studies; Humans; Leucine; Leukemia; Mercaptopurine; Middle Aged; Naphthacenes; Prednisolone; Prognosis; Random Allocation

Ubenimex (Bestatin, Ubx) has been shown to have anti-tumor activity and immuno-modulating activities. Ubx has been used in immuno-therapy in combination with remission maintenance chemotherapy after induction of complete remission for adult acute non-lymphocytic leukemia (ANLL, AML). Daunomycin (DNR), arabinosylcytosine (Ara-C) and 6-mercaptopurine (6-MP) are used for the standard chemotherapy for ANLL. It is, however, believed that emergence of resistant cells to chemotherapy cause minimal residual leukemia resulting in poor prognosis. Ubx has been administered in combination with these chemotherapeutic agents. We examined the combinatorial effect of Ubx with DNR, Ara-C, 6-MP and etoposide on K562 leukemic cell line and the chemotherapeutic agent resistant cells derived from K562 cell line. Ubx showed growth inhibitory effects on these cell lines. A synergistic effect was observed on growth inhibition and with colony formation of parent k562 cell line when DNR and Ubx were used in combination. A combination of Ubx with Ara-C or etoposide showed additional effects on parent cells and other resistant cell lines. The combined growth inhibitory effect of 6-MP and Ubx was stronger than the effect of 6-MP alone. These results show that Ubx has a direct growth inhibitory effect on leukemic cells and additional or synergistic effects are obtained on K562 leukemic cell line and on chemotherapeutic agent resistant cells derived from the K562 cell line when Ubx is used combination with the above chemotherapeutic agents.

Topics: Antibiotics, Antineoplastic; Antineoplastic Agents; Cell Division; Cytarabine; Daunorubicin; Depression, Chemical; Drug Combinations; Drug Resistance, Neoplasm; Drug Synergism; Humans; Leucine; Leukemia, Myeloid, Acute; Mercaptopurine; Tumor Cells, Cultured