Phase 1 trial of intraperitoneal AD-32 in gynecologic malignancies.
AD-32 (N-trifluoroacetyladriamycin-14-valerate), an analogue of doxorubicin, 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/m2, the limiting toxicity was grade 4 neutropenia (64% of patients), while severe abdominal pain was relatively uncommon (12%). Intraperitoneal AD-32 administration was associated with a 200-fold pharmacokinetic advantage for cavity exposure, compared to the systemic compartment. At the 600 mg/m2 dose level, 4 of 9 patients (44%) with ascites experienced control of malignant fluid reaccumulation. Based on the results of this phase 1 trial, further exploration of a possible role for the ip administration of AD-32 in individuals with gynecological malignancies appears indicated, particularly in patients with either small volume residual disease after initial systemic chemotherapy or in those with intractable ascites.
Markman
M
M
The Cleveland Clinic Foundation, Ohio 44195, USA.
Homesley
H
H
Norberts
D A
DA
Schink
J
J
Abbas
F
F
Miller
A
A
Soper
J
J
Teng
N
N
Hammond
N
N
Muggia
F
F
Israel
M
M
Sweatman
T
T
D000368:Aged; D000369:Aged, 80 and over; D001772:Blood Cell Count / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D005260:Female; D005833:Genital Neoplasms, Female / Q000188:drug therapy* / Q000378:metabolism*; D006801:Humans; D007274:Injections, Intraperitoneal; D008875:Middle Aged; D016896:Treatment Outcome
C016163:valrubicin; D004317:Doxorubicin