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- W2048986656 abstract "Abstract WR-2721 is an organic thiophosphate which in the animal model provides selective protection of normal tissues against the toxicity of radiation and alkylating agent chemotherapy. Phase I trials of WR-2721 in man have been initiated to establish the dose modification factors for this agent when used in combination with escalating doses of alkylating agents beyond the level currently tolerated, and to determine whether protection of normal tissues and tumors occurs. Three Phase I trials are in progress. Initially, we used a fixed 450 mg/M2 dose of WR-2721 prior to escalating doses of either cyclophosphamide (CYC) or cis-platinum (PL) as single agents. More recently, the current maximum tolerated dose of WR-2721(740 mg/M2) was administered prior to PL and to nitrogen mustard (HN2). Ten patients received 19 courses of CYC after 450 mg/M2 of WR-2721. At the 1800 mg/M2 LV. dose level of CYC, moderate leukopenia was noted with a median WBC nadir of 1800/mm3 on day 10. Twenty-two courses of PL were administered to 13, patients after 450–740 mg/M2 of WR-2721. Hydration was used, but no mannitol diuresis was employed. Transient nephrotoxicity was noted in five courses at PL doses between 80–120 mg/M2. Mild to moderate leukopenia has been noted with HN2 at 10–16 mg/M2 following WR-2721 (450–750 mg/M2). Objective anti-tumor responses have been observed. These preliminary results suggest that WR-2721 may provide normal tissue protection when administered prior to cyclophosphamide or nitrogen mustard, although the level of protection is not yet of clinical benefit. However, using a 450–740 mg/M2 dose of WR-2721 did not provide protection against platinum-induced nephrotoxicity. WR-2721 does not appear to protect against the anti-tumor activity of alkylating agents (objective tumor responses were noted), nor does there appear to be increased acute toxicity when it is combined with alkylating agent chemotherapy." @default.
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- W2048986656 date "1982-03-01" @default.
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- W2048986656 title "Phase I clinical trials of WR-2721 with alkylating agent chemotherapy" @default.
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- W2048986656 doi "https://doi.org/10.1016/0360-3016(82)90687-3" @default.
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