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- W1993903180 abstract "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 hematologic toxicity. Fifteen patients received WR-2721 (450–1100 mg/m2) prior to cyclophosphamide (1200–1800 mg/m2) and were subsequently retreated 4 weeks later with the same cyclophosphamide dose alone. With WR-2721 pretreatment, (73%) patients had improved WBC counts. The mean WBC increased from 1800/mm3 on cyclophosphamide alone to 2700/mm3 with WR-2721 + cyclophosphamide (p = 0.008). In 11 patients who had nadir differential counts performed, 7 64% demonstrated improved nadir granulocyte counts with WR-2721. The mean granulocyte count increased from 765/mm3 on cyclophosphamide to 1274/mm3 with WR-2721 + cyclophosphamide (p = 0.05). In the second trial, 25 patients received the reverse sequence: an initial dose of cyclophosphamide (1200–1800 mg/m2) alone, followed 4 weeks later by WR-2721 (450–1100 mg/m2) prior to the same dose of cyclophosphamide. With WR-2721 pretreatment, (48%) patients had improved nadir WBC counts. The mean WBC increased from 1550/mm3 on cyclophosphamide alone to 1850/mm3 with WR-2721 + cyclophosphamide (p = 0.02), while the nadir granulocyte count increased from 449/mm3 to 844/mm3 (p = 0.001). No patient developed microscopic or gross hematuria or inappropriate antidiuretic hormone secretion. One patient developed mild thrombocytopenia. 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/m2 administered over 15 minutes." @default.
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- W1993903180 date "1984-09-01" @default.
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- W1993903180 title "Phase I Controlled trials of WR-2721 and cyclophosphamide" @default.
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- W1993903180 doi "https://doi.org/10.1016/0360-3016(84)90548-0" @default.
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