km-2210 and Leukemia--Myeloid

Twenty-one patients were entered for a clinical study of KM 2210, the benzoate of an estradiol-chlorambucil conjugate, in the treatment of hematopoietic malignancies. These included 4 cases of chronic lymphocytic leukemia (CLL), 5 cases of chronic myelogenous leukemia (CML), 5 cases of malignant lymphoma (ML) and 7 cases of multiple myeloma (MM). Twelve cases had prior chemotherapy. KM 2210 was given orally at a dose of 50-300 mg daily. Of 19 evaluable cases, two cases with CLL achieved complete response and 6 cases including 2 with CLL, 2 with CML and 3 with ML achieved partial response. There were no responders among the cases of MM. The partial and complete response rate was 47%. Toxicity included mild breast or nipple pain (28.6%), genital bleeding (9.5%), appetite loss (9.5%) and gynecomastia (4.8%). These side effects may have been due to increased levels of estrogen. Hematopoietic toxicity was mild and well tolerated. No cardiac, hepatic or renal toxicity was observed in this study. These results suggest that KM 2210 might be an effective candidate for the treatment of hematopoietic malignancies, especially CLL.

Topics: Aged; Chlorambucil; Clinical Trials as Topic; Drug Administration Schedule; Estradiol; Female; Humans; Leukemia, Lymphoid; Leukemia, Myeloid; Lymphoma; Male; Middle Aged; Multiple Myeloma

Thirty-three patients with various hematological malignancies were treated with Bestrabucil, the benzoate of an estradiol-chlorambucil conjugate, at doses of 50-300 mg daily p.o., consecutively. Nineteen patients had previously received chemotherapy. Of 29 evaluable patients, there were one CR and three PRs among 6 patients with chronic lymphocytic leukemia, two CRs and one PR among 4 patients with malignant lymphoma, two PRs among 3 patients with adult T-cell leukemia, one PR among 4 patients with macroglobulinemia, one PR for one patient with essential thrombocythemia, and one PR for a patient with chronic myelocytic leukemia. Main side effects included G1 symptoms (14%), estradiol-related symptoms (24%) and myelosuppression (32%).

Topics: Adult; Aged; Chlorambucil; Drug Administration Schedule; Drug Evaluation; Estradiol; Female; Humans; Leukemia, Lymphoid; Leukemia, Myeloid; Leukopenia; Lymphoma; Male; Middle Aged; Thrombocytopenia