Therapeutic Effect of Leo 1031, an Alkylating Corticosteroid Ester, in Lymphoproliferative Disorders

Abstract

Leo 1031, a chlorambucil ester of pred nisolone, has been administered orally to 15 patients with chronic lymphocytic leukaemia (CLL) continuously for 1–29 months (mean 12.5). Seven patients were previously untreated and eight had been treated with prednisolone, radiotherapy and/or alkylating agents. The initial daily dose was generally 8–16 mg and the maintenance dose was 6–8 mg. Allopurinol was given concurrently. In 14 of 15 patients a reduction of the leucocyte count was observed and a reduction, in most instances, of lymphadenopathy or splenomegaly, or both. In seven patients the Hb concentration was improved. Significant toxic effects on bone marrow function have been observed in one patient. Two patients developed urticaria. Our study suggests that the drug is effective in the treatment of CLL.

Clinical Trial of Prednimustine, Leo‐1031 (NSC‐134087), in Patients with Non‐Hodgkin Lymphomata and Chronic Lymphocytic Leukaemia Previously Treated with Steroids and Alkylating Agents

“…So far the most promising results have been obtained in lymphoid neoplasias: a 75 % response rate both in patients with CLL (3,5,8 and present study) and in NHL of lymphocytic type (Table IV). This response frequency is remarkably high in view of the fact that many patients had received extensive prior treatment, including alkylating agents.…”

“…In preliminary investigations in humans the drug has so far revealed an antineoplastic effect in a high percentage of patients with chronic lymphocytic leukaemia (CLL) (3,5,8), non-Hodgkin lymphomata (NHL) mainly of the lymphocytic type ( 5 , 6 . 8.…”

Structure–antileukemic activity relationship study of B- and D-ring modified and nonmodified steroidal esters of 4-methyl-3-N,N-bis(2-chloroethyl)amino benzoic acid: a comparative study

“…The discovery of steroid hormone receptors and hormone responsiveness in a series of human tumors [7][8][9][10] offers the opportunity for targeting using drug-hormone conjugates [11][12][13][14][15]. The initial approach used for the design of complex molecules, comprising a nitrogen mustard and a steroidal skeleton, was based on the concept that the steroidal part would act as a 'biological platform' enabling the alkylating moiety to approach its site of action by altering its physicochemical properties (e.g.…”

Mammary Tumour Inhibition and Subacute Toxicity in Rats of Prednimustine and of Its Molecular Components Chlorambucil and Prednisolone

“…1). The clinical trials with this ester indicate that prednimustine is a safe and effective drug for long-term oral treatment of lymphocytic lymphoma and chronic lymphocytic leukemia (Aungst et al 1975;Brandt et al 1975;Moller et al 1975;Kaufman 1976). The effect of chlorambucil and et al prednisolone on metastatic carcinoma of the breast (Freckman et al 1964) suggests that prednimustine may be of value in the treatment of this malignancy.…”