Journal of Clinical Oncology, Vol 1, 198-203, Copyright © 1983 by American Society of Clinical Oncology
Clinical trial of the effect of S-2-(3-aminopropylamino)- ethylphosphorothioic acid (WR-2721) (NSC 296961) on the toxicity of cyclophosphamide
PV Woolley 3d, MJ Ayoob, FP Smith and A Dritschilo
S-2-(3-Aminopropylamino)-ethylphosphorothioic acid (WR-2721) is reported to
protect normal tissues from the effects of ionizing radiation and possibly
alkylating agents as well. The present trial assessed the ability of this
compound to modify the clinical toxicity of cyclophosphamide. Patients with
advanced cancer first received a dose of 1000 mg/m2 cyclophosphamide
intravenously and were observed for toxicity, principally myelosuppression.
After the nadir in white blood cell counts and/or platelets had been
documented and adequate recovery had occurred, a second course of
cyclophosphamide was given, this time preceded by WR-2721 30 min earlier.
In this fashion, each patient served as his own control. Doses of WR-2721
ranging from 250 to 1000 mg/m2 were tested. A total of 13 evaluable courses
of WR-2721 were given with cyclophosphamide. In no instance did the prior
administration of WR-2721 diminish the bone marrow toxicity of
cyclophosphamide alone. At the end of the trial two additional patients
received the WR-2721 in a split dose, one-half prior to the
cyclophosphamide and one-half 6 hr later; again there was no protection.
The side effects of WR-2721 included nausea, vomiting, hypotension,
sneezing, and swelling of the tongue. We conclude that WR- 2721 is a
potentially toxic compound that produces no amelioration of
cyclophosphamide toxicity in the doses used. Because of the severity of the
side effects of WR-2721, principally hypotension, the trial was terminated
after 1000 mg/m2 WR-2721 failed to protect against the toxicity of 1000
mg/m2 cyclophosphamide.
