Clinical trial of the effect of S-2-(3-aminopropylamino)-ethylphosphorothioic acid (WR-2721) (NSC 296961) on the toxicity of cyclophosphamide.
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.
D000328:Adult; D000368:Aged; D004999:Amifostine / Q000009:adverse effects / Q000494:pharmacology*; D001853:Bone Marrow / Q000187:drug effects; D002986:Clinical Trials as Topic; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000009:adverse effects*; D004347:Drug Interactions; D004359:Drug Therapy, Combination; D006801:Humans; D007022:Hypotension / Q000139:chemically induced*; D007970:Leukopenia / Q000139:chemically induced*; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy*; D009946:Organothiophosphorus Compounds / Q000494:pharmacology*
D009946:Organothiophosphorus Compounds; D003520:Cyclophosphamide; D004999:Amifostine