mercaptopurine and ranimustine

Seventeen patients with myeloproliferative disorders and one patient with chronic myelomonocytic leukemia (CMMoL) were treated with ranimustine++ (MCNU), and the efficacy was evaluated. MCNU was given intravenously by drip infusion at an usual dose of 100 approximately 150 mg with intervals arranged according to the counts of peripheral blood cells. A complete remission was achieved in all 10 patients with chronic myelogenous leukemia (CML) in chronic phase. In three of patients with polycythemia vera (PV) the excellent effects were obtained, and the other 2 cases showed moderate effect. An excellent effect was obtained in both 2 patients with essential thrombocythemia (ET). A patient with CMMoL revealed partial remission. The overall efficacy rate was 100%. The cases with CML needed more long term and much more dose of the drug in order to get remission compared with PV and ET. After remission in both PV and ET, well controlled states were maintained for a relatively long period with no additional administration. In CMMoL, MCNU combined with 6-mercaptopurine also showed remarkable anti-tumor effects. It suggests that MCNU may be one of the useful drugs for the treatment of CMMoL. The side effects observed with MCNU were a slight degree of nausea and vomiting (28%), however they showed no trouble on carrying out the therapy.

Topics: Adult; Aged; Antineoplastic Agents; Drug Administration Schedule; Female; Humans; Infusions, Intravenous; Leukemia, Myelomonocytic, Chronic; Male; Mercaptopurine; Middle Aged; Myeloproliferative Disorders; Nitrosourea Compounds; Remission Induction

Seventy-four patients in the chronic phase of Ph1-positive chronic myelogenous leukemia (CML) have been treated with busulfan or other alkylating agents in a conventional way. During its chronic phase, 24 of these 74 cases had received additional intermittent therapy every 4 to 6 months, consisting of vincristine 2 mg or vindesine 3 mg per week, prednisolone 20-30 mg per day and partly 6 mercaptopurine 50 to 100 mg, combined with allopurinol 200 to 300 mg per day for 2 to 3 weeks. The 50% survival of these patients using the Kaplan-Meier's method was 73.7 months and 5-year survival was 69.6%, against 40.5 months and 14.4%, respectively, in the remaining patients. Nine patients in the blastic or accelerated phase of Ph1-positive CML have been treated with new regimens including MCNU. All cases had been refractory for usual types of induction chemotherapy. The new regimen consisted of MCNU 50-100 mg, combined with vindesine or 6-MP plus allopurinol or prednisolone. Five out of 9 cases attained complete remission and 1 partial remission. The major adverse effect of this regimen was slight liver damage. MCNU could be regarded as an useful agent in the blastic phase as well as in the chronic phase of CML.

Topics: Adolescent; Adult; Aged; Allopurinol; Antineoplastic Combined Chemotherapy Protocols; Blast Crisis; Drug Evaluation; Female; Humans; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Leukemia, Myeloid, Accelerated Phase; Leukemia, Myeloid, Chronic-Phase; Male; Mercaptopurine; Middle Aged; Nitrosourea Compounds; Prednisolone; Remission Induction; Vincristine; Vindesine

Combination chemotherapy using the water-soluble nitrosourea MCNU with various anti-cancer agents was studied using L1210 leukemia and P388 leukemia. In titration experiments MCNU showed remarkable antitumor effects at doses from 5 mg/kg to 80 mg/kg, producing numbers of 60-day survivors with L1210 leukemia. In L1210 leukemia, respective combinations of MCNU with the antimetabolites, MTX, 6-MP, 6-TG, MCNU, 5-FU and Cyclo-C showed enhanced antitumor effects. MCNU combined with each of ADR, MMC and CPM also showed marked anti-tumor effects with 60-day survivors. In P388 leukemia MCNU combined with each of ADR, MMC, VDS and CPM produced strong anti-tumor effects with numbers of 60-day survivors. In the results of these combinations, especially the combinations of MCNU + 5-FU in L1210 leukemia and MCNU + CPM in both L1210 and P388 leukemia, a significant increase in mean survival time was achieved. These combinations also produced many 60-day survivors which were considered to be due to the synergistic antitumor effects of the combined drugs.

Topics: Animals; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Cytarabine; Doxorubicin; Female; Fluorouracil; Leukemia L1210; Leukemia P388; Leukemia, Experimental; Mercaptopurine; Methotrexate; Mice; Mice, Inbred DBA; Mitomycin; Mitomycins; Nitrosourea Compounds; Thioguanine