PHASE-1 TRIAL OF INTRAPERITONEAL AD-32 IN GYNECOLOGIC MALIGNANCIES

AD-32 (N-trifluoroacetyladriamycin-14-valerate), an analogue of doxoru bicin, was examined for intraperitoneal (ip) administration in a phase 2 trial involving 25 patients with advanced gynecologic malignancies. At an AD-32 dose of 600 mg/m(2), the limiting toxicity was grade 4 ne utropenia (64% of patients), while severe abdominal pain was relativel y uncommon (12%). Intraperitoneal AD-32 administration was associated with a 200-fold pharmacokinetic advantage for cavity exposure, compare d to the systemic compartment. At the 600 mg/m(2) dose level, 4 of 9 p atients (44%) with ascites experienced control of malignant fluid reac cumulation. Based on the results of this phase 1 trial, further explor ation of a possible role for the ip administration of AD-32 in individ uals with gynecological malignancies appears indicated, particularly i n patients with either small volume residual disease after initial sys temic chemotherapy or in those with intractable ascites. (C) 1996 Acad emic Press, Inc.