Carboxypeptidase-G2 (CPDG2) and leucovorin (LV) rescue with and without addition of thymidine (Thd) for high-dose methotrexate (HDMTX) induced renal dysfunction

2076 Background: We previously demonstrated that CPDG2, which rapidly hydrolyzes MTX to inactive metabolites, when combined with LV and Thd, effectively rescues patients (pts) with HDMTX-induced nephrotoxicity. This study assessed the role of Thd administration in these pts. Methods: Pts (n=100) with HDMTX-induced renal dysfunction and significantly delayed MTX clearance received 1–3 doses of CPDG2, 50 U/kg IV, and standard LV rescue. In the initial cohort pts (n=35) also received 8 g/m2/d of Thd by continuous IV infusion. Subsequently, Thd was restricted to pts with prolonged (> 96 hours) exposure to MTX or with severe MTX toxicity at study entry (n=9). Plasma MTX concentrations (available in 75 pts), MTX associated toxicities, and outcome were compared in pts who did (Thd+) vs. did not (Thd-) receive Thd. Results: CPDG2 was administered at a median of 96 and 66 hours after start of the MTX infusion in Thd+ (n=44) or Thd- (n=54) pts, respectively. Median plasma MTX concentrations measured by HPLC pre CPD...