Blood Journal
Leading the way in experimental and clinical research in hematology

A Controlled Trial of Urethane Treatment in Multiple Myeloma

  1. JAMES F. HOLLAND, M.D.,
  2. HENRY HOSLEY, M.D.,
  3. CAROL SCHARLAU,
  4. PAUL P. CARBONE, M.D.,
  5. EMIL FREI III, M.D.,
  6. CLYDE O. BRINDLEY, M.D.,
  7. THOMAS C. HALL, M.D., Medical Service,
  8. BRUCE I. SHNIDER, M.D.,
  9. G. LENNARD GOLD, M.D.,
  10. LOUIS LASAGNA, M.D.,
  11. ALBERT H. OWENS JR., M.D., and
  12. SHERWOOD P. MILLER, M.D.
  1. Dept. of Medicine, A Roswell Park Memorial institute, N. Y. State Department of Health, Buffalo, N. Y. (CA-02821).
  2. Same affiliation as Dr. Holland. Present address: Albany Medical College of Union University, Albany, N. Y.
  3. Same affiliation as Dr. Holland.
  4. Medicine Branch, National Cancer Institute, National institutes of Health, Bethesda, Md.
  5. Same affiliation as Dr. Carbone. Present address: Tile University of Texas, M.D. Anderson Hospital and Tumor Institute, houston, Tex.
  6. Same affiliation as Dr. Carbone. Present address: V. A. Center, Mountain Home, Tenn.
  7. Lemuel Shattuck Hospital, Dept. of Public Health, Commonwealth of Massachusetts; Dept. of Medicine, Harvard Medical School, Boston, Mass. (CA-071 90). Present address: Children's Cancer Research Foundation, Boston, Mass.
  8. Georgetown University Medical Division, D. C. General Hospital; Dept. of Medicine, Georgetown University School of Medicine; Mt. Alto V. A. Hospital, Washington, D. C. (CA-02824).
  9. Same affiliation as Dr. Shnider.
  10. Dept. of Medicine, The Johns Hopkins University, School of Medicine, Baltimore, Md. (CA-02822).
  11. Same affiliation as Dr. Lasagna.
  12. Dept. of Medicine, Maimonides Hospital of Brooklyn, Brooklyn, N. Y. (CA-05588).

Abstract

Patients with multiple myeloma were stratified according to prior treatment and randomly assigned to coded urethane or placebo syrup administration. Urethane administration was of shorter duration than placebo treatment, but was associated, in patients who received 100 Gm. or more, with leukopenia in the last half of treatment courses. All recognizable beneficial effects were extracted from individual case histories and were found to be nearly equally distributed between the two treatments. Interpretation of the causes of clinical benefit was difficult but there was close temporal relationship to radiation, antibiotics for infection, or corticosteroid administration. Some clinical features and laboratory data of 36 patients with placebo-treated multiple myeloma are provided.

Urethane-treated patients died somewhat earlier on the average than those treated with placebo. This was ascribable in large part to accelerated mortality in urethane-treated patients who were azotemic.

When hemoglobin concentration, marrow plasma cell content, performance status and azotemia were used to construct a relative ranking prognostic index, among the two-thirds of patients with the worst indexes significantly shorter survival was associated with urethane treatment (p < .05). In the best prognostic class, no difference was observed in the survival of urethane- or placebo-treated patients.

Since urethane administration was in no way superior to placebo administration, and was characterized by shortened survival, its use in the doses and schedule employed in this study would appear ill advised.

  • Submitted March 18, 1965.
  • Accepted June 18, 1965.