Clinical response to busramustine (KM-2210) in chronic lymphocytic leukemia: a pilot evaluation of estrogen receptor in relation to its therapeutic effect

Jpn J Clin Oncol. 1988 Dec;18(4):327-33.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Blood Coagulation / drug effects
  • Chlorambucil / adverse effects
  • Chlorambucil / analogs & derivatives*
  • Chlorambucil / therapeutic use
  • Estradiol / adverse effects
  • Estradiol / analogs & derivatives*
  • Estradiol / therapeutic use
  • Female
  • Humans
  • Leukemia, Lymphocytic, Chronic, B-Cell / drug therapy*
  • Leukemia, Lymphocytic, Chronic, B-Cell / metabolism
  • Male
  • Middle Aged
  • Receptors, Estrogen / drug effects*

Substances

  • Receptors, Estrogen
  • Chlorambucil
  • Estradiol
  • bestrabucil