Clinical response to busramustine (KM-2210) in chronic lymphocytic leukemia: a pilot evaluation of estrogen receptor in relation to its therapeutic effect.
Busramustine (KM-2210), the benzoate of a 17 beta-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.
Nishikawa
M
M
Second Department of Internal Medicine, Mie University School of Medicine.
Uemura
Y
Y
Komada
F
F
Ohno
T
T
Katayama
N
N
Shirakawa
S
S
D000328:Adult; D000368:Aged; D001777:Blood Coagulation / Q000187:drug effects; D002699:Chlorambucil / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D004958:Estradiol / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D005260:Female; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000188:drug therapy* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D011960:Receptors, Estrogen / Q000187:drug effects*
D011960:Receptors, Estrogen; D002699:Chlorambucil; D004958:Estradiol; C036613:bestrabucil