2555 Background: Dexrazoxane prevented tissue necrosis in 98% of patients (pts) with biopsy proven anthracycline extravasation (AEV) in two international multicenter studies, TT01 and TT02 (Mouridsen HT et al Ann Onc Advance Access Dec 21, 2006). However, the pharmacokinetics (PK) of IV dexrazoxane in the three-day schedule is not established. Study TT04 was initiated to investigate PK. Patients and methods: TT04 is a prospective, open-label, single-arm, multicenter studies in pts with AEV. Consecutive pts with AEV are treated with a three-day schedule of IV dexrazoxane (1,000, 1,000, and 500 mg/m2) starting within 6 hr of AEV. Primary objective: Establish PK of IV dexrazoxane in the three-day schedule. Secondary objectives: obtaining additional efficacy and safety data. Plasma samples at 0, 1, 2, 4 and 24 hr day 1–3 are analyzed by HPLC-MS. PK parameters were calculated by a non compartmental method. TT01 and TT02 were open-label, single-arm, multicenter studies enrolling pts with biopsy proven AEV from 24 EU centers. Primary objective was to avoid tissue necrosis leading to surgery. Secondary objectives were to minimize delay of planned chemotherapy, reduce hospitalization, and avoid long term sequelae. Results: Six pts have entered the PK study. The average elimination was T½ ± SD of 127 ± 23, 144 ± 21, and 107 ± 29 min, day 1, 2 and 3, respectively. Pre-dose concentrations day 2 and 3 are = LOQ. Average AUC 0-t ± SD are 193 ± 93 (t= 24 hr), 196 ± 101 (t= 24 hr), and 46 ± 24 μg hr/ml (t= 4 hr), on day 1, 2 and 3, respectively. Cumulative data from the 3 studies: Surgery was avoided in 59/60 pts (98.3%). No delay in planned chemotherapy in 71%. 41% were hospitalized (median 3 days) due to the EV or its treatment. Mild pain (19%) and mild sensory disturbances (17%) were the most frequent sequelae: Reversible CTC grade 3–4 leucopenia/neutropenia in 45%, thrombocytopenia in 21% of the pts. Conclusion: There was no accumulation of dexrazoxane during the three-day schedule. Dexrazoxane was well tolerated and highly effective against anthracycline extravasation. Updated results will be presented. No significant financial relationships to disclose.
Read full abstract