Phase I controlled trials of WR-2721 and cyclophosphamide

Conference · Sat Sep 01 00:00:00 EDT 1984 · Int. J. Radiat. Oncol., Biol. Phys.; (United States)

OSTI ID:6166463

Glick, J H; Glover, D; Weiler, C; Norfleet, L; Yuhas, J; Kligerman, M M

WR-2721 is an organic thiophosphate compound which in the animal model selectively protects against the hematologic toxicity of cyclophosphamide by factors of 1.5 to 2.0. Controlled Phase I trials of WR-2721 and cyclophosphamide were initiated to determine if WR-2721 protected against cyclophosphamide's hematolgic toxicity. Fifteen patients received WR-2721 prior to cyclophosphamide and were subsequently retreated 4 weeks later with the same cyclophosphamide dose alone. With WR-2721 pretreatment, 11/15 (73%) patients had improved WBC counts. In the second trial, 25 patients received the reverse sequence: an initial dose of cyclophosphamide alone, followed 4 weeks later by WR-2721 prior to the same dose of cyclophosphamide. With WR-2721 pretreatment, 12/25 (48%) patients had improved nadir WBC counts. No patient developed microscopic or gross hematuria or inappropriate antidiuretic hormone secretion. These data suggest that WR-2721 provides significant protection against cyclophosphamide-induced granulocytopenia, but the dose modification factors and degree of clinical benefit remain to be established. The current recommended WR-2721 dose for Phase II trials is 740 mg/m/sup 2/ administered over 15 minutes.

• Research Organization: Univ. of Pennsylvania, Philadelphia
• OSTI ID: 6166463
• Report Number(s): CONF-8311204-
• Journal Information: Int. J. Radiat. Oncol., Biol. Phys.; (United States), Vol. 10:9; Conference: Conference on chemical modifiers of cancer treatment, Banff, Alberta, Canada, 27 Nov 1983
• Country of Publication: United States
• Language: English

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