isotretinoin and Leukemia--Myeloid

13-cis retinoic acid + (OH)2 vitamin D3 + low-dose 6-thioguanine and cytarabine were tested in 26 patients with acute myeloid leukemia (AML) and in 4 patients with myelodysplastic syndrome (MDS) (median age 72.5), ineligible for standard chemotherapy. The response rate was 50%, with 27% complete remission. The median survival of the whole group and responders was 7.5 (1-47+) and 16.5 months (3.5-47+), respectively.

Topics: Acute Disease; Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Calcitriol; Cytarabine; Disease Progression; Female; Humans; Isotretinoin; Leukemia, Myeloid; Male; Middle Aged; Myelodysplastic Syndromes; Thioguanine

Treatment of chronic phase chronic myelogenous leukemia with hydroxyurea or busulfan rarely induces cytogenetic (true) remissions. Intensive chemotherapy induces brief true remissions in approximately 50% of patients. We added 13-cis-retinoic acid to daunorubicin, cytosine arabinoside, and thioguanine to determine if it could increase the incidence and duration of remission induced by cytotoxic chemotherapy. Of the 17 evaluable patients, one patient (6%) achieved complete remission, and seven patients (41%) achieved partial remissions. The median duration of remission was 1.6 months. We conclude that 13-cis-retinoic acid does not increase the incidence and duration of remission in chronic phase chronic myelogenous leukemia.

Topics: Adolescent; Adult; Antineoplastic Combined Chemotherapy Protocols; Bone Marrow; Chromosomes, Human, 21-22 and Y; Cytarabine; Daunorubicin; Humans; Isotretinoin; Leukemia, Myeloid; Leukopenia; Liver; Middle Aged; Stomatitis; Thioguanine; Thrombocytopenia; Time Factors; Tretinoin

Eighteen patients with myelodysplastic syndrome received 13-cis-retinoic acid (1.0-mg/kg/day starting dose with 0.5-mg/kg increment escalations) in a phase I-II trial. Two partial responses involving the erythroid series were observed in four patients with primary refractory anemia with ring sideroblasts. One of two patients with chronic myelomonocytic leukemia also achieved a partial response. No other responses were found in the remaining patients, which included eight with refractory anemia with excess blasts. In six patients drug toxicity necessitated termination of the trial. Four patients had unexpected drug-induced thrombocytopenia; three of these had low platelet counts before treatment. Two of the six patients had other toxic effects. Further studies are warranted to evaluate the effectiveness of 13-cis-retinoic acid in patients with refractory anemia with ring sideroblasts and chronic myelomonocytic leukemia. At moderate doses significant toxic effects, including thrombocytopenia, are not uncommon.

Topics: Anemia, Refractory; Blood Cell Count; Drug Evaluation; Erythropoiesis; Hematopoietic Stem Cells; Hemoglobins; Humans; Isotretinoin; Leukemia, Myeloid; Myelodysplastic Syndromes; Thrombocytopenia; Tretinoin

Topics: Animals; Calcitriol; Cell Differentiation; Cell Line; Colony-Forming Units Assay; Endotoxins; Humans; Isotretinoin; Kinetics; Leukemia, Experimental; Leukemia, Myeloid; Macrophages; Mice; Neutrophils; Tretinoin

13-cis-Retinoic acid (13-cRA) induces maturation and differentiation of neoplastic myeloid cell lines in vitro. We conducted a phase I clinical trial of 13-cRA in patients with myelodysplastic syndromes (MDS), using a single daily oral dose schedule. Seventeen patients with MDS and one each with acute nonlymphoblastic leukemia and chronic myelogenous leukemia in blast crisis were treated with 13-cRA at doses ranging from 20 to 125 mg/m2/day. Hepatotoxicity was dose-limiting and was manifested by hyperbilirubinemia and increased SGOT levels. This effect was seen only at the highest dose level of 125 mg/m2/day and was completely reversible upon cessation of the drug. Other toxic effects were mild, and included cheilosis, hyperkeratosis, stomatitis, and elevation of serum triglyceride levels. Fifteen patients with MDS were evaluable for therapeutic response. Five patients showed improvement in hematologic parameters. These responses included normalization of bone marrow blast count and increases in leukocyte count, platelet count, and/or hemoglobin concentration. Responses were generally not seen until at least 3 weeks of therapy were completed. We conclude that further study of 13-cRA in myelodysplastic syndromes is warranted and recommend that future studies utilize a starting dose of 100 mg/m2.

Topics: Administration, Oral; Adult; Aged; Blood Cell Count; Dose-Response Relationship, Drug; Drug Evaluation; Female; Humans; Isotretinoin; Leukemia, Myeloid; Liver; Male; Middle Aged; Myeloproliferative Disorders; Preleukemia; Tretinoin