Clinical Response to Busramustine (KM-2210) in Chronic Lymphocytic Leukemia: A Pilot Evaluation of Estrogen Receptor in Relation to Its Therapeutic Effect

• Published in: Japanese journal of clinical oncology 1988-12, Vol.18 (4), p.327-333
• Main Authors: Nishikawa, Masakatsu, Uemura, Yasuhiro, Komada, Fumihiko, Ohno, Toshiyuki, Katayama, Naoyuki, Shirakawa, Shigeru
• Format: Article
• Language: English
• Subjects: Adult; Aged; Blood Coagulation - drug effects; Busramustine; Chemotherapy; Chlorambucil - adverse effects; Chlorambucil - analogs & derivatives; Chlorambucil - therapeutic use; Chronic lymphocytic leukemia; Estradiol - adverse effects; Estradiol - analogs & derivatives; Estradiol - therapeutic use; Estrogen receptor; Female; Humans; Leukemia, Lymphocytic, Chronic, B-Cell - drug therapy; Leukemia, Lymphocytic, Chronic, B-Cell - metabolism; Male; Middle Aged; Receptors, Estrogen - drug effects
• ISSN: 0368-2811; 1465-3621; 1465-3621
• DOI: 10.1093/oxfordjournals.jjco.a039256

Busramustine (KM-2210), the benzoate of a 17β-estradiol-chlorambucil conjugate,$$$ was administered to 11 patients with chronic lymphocytic leukemia (CLL) which included eight cases of B-cell CLL and three cases of T-cell CLL. Four patients had received prior chemotherapy. Busramustine was given orally at an initial daily dose of 50–100 mg continuously, and the dose was modified according to hematological improvement. Two cases of B-cell CLL achieved clinical complete responses, six cases including two of T-cell CLL and four of B-cell CLL achieved partial responses and one case of B-cell CLL achieved improvement. The partial and complete response rate was 72.7%. Four patients showed estrogen receptor activity of CLL cells ranging from 3.5 to 57.5 fmol/mg cytosol protein, but there seemed to be no correlation between the estrogen receptor activity of the CLL cells and the therapeutic effects of busramustine. Toxic effects included diarrhea (2/11) and estrogen-related symptoms including breast pain (4/11), genital bleeding (2/5), gynecomastia (2/6) and loss of libido (2/6). The findings of this preliminary study suggest that busramustine is effective in the treatment of CLL, irrespective of the presence of the estrogen receptor.