Abstract
INO-1001 is a PARP-1 inhibitor that interrupts the repair process of N-methylpurines generated by temozolomide. We evaluated the pharmacokinetics of INO-1001 and determined its safety when used with temozolomide at 200 mg/m(2)/day x 5 days every 4 weeks. We enrolled 12 adult patients, in cohorts of 3-6 patients, into the study. INO-1001 at doses of 100, 200 and 400 mg was given intravenous for 1 hr q 12 hr for 10 doses. INO-1001 had a moderate clearance, volume of distribution and a relatively short terminal half-life. Myelosuppression and elevation of liver transaminases were dose-limiting toxicities (DLTs) of INO-1001 at 400 mg.
Publication types
-
Clinical Trial, Phase I
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Administration, Oral
-
Aged
-
Antineoplastic Combined Chemotherapy Protocols / adverse effects
-
Antineoplastic Combined Chemotherapy Protocols / pharmacokinetics
-
Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
-
Bone Marrow Diseases / chemically induced
-
Chemical and Drug Induced Liver Injury / diagnosis
-
Chemical and Drug Induced Liver Injury / etiology
-
DNA Mismatch Repair
-
Dacarbazine / administration & dosage
-
Dacarbazine / adverse effects
-
Dacarbazine / analogs & derivatives
-
Dacarbazine / pharmacokinetics
-
Dacarbazine / pharmacology
-
Drug Administration Schedule
-
Female
-
Humans
-
Indoles / administration & dosage
-
Indoles / adverse effects
-
Indoles / pharmacokinetics
-
Indoles / pharmacology
-
Infusions, Intravenous
-
Male
-
Melanoma / drug therapy*
-
Melanoma / secondary*
-
Middle Aged
-
Neoplasm Proteins / antagonists & inhibitors*
-
Neoplasm Proteins / physiology
-
Poly (ADP-Ribose) Polymerase-1
-
Poly(ADP-ribose) Polymerase Inhibitors*
-
Poly(ADP-ribose) Polymerases / physiology
-
Temozolomide
Substances
-
INO 1001
-
Indoles
-
Neoplasm Proteins
-
Poly(ADP-ribose) Polymerase Inhibitors
-
Dacarbazine
-
PARP1 protein, human
-
Poly (ADP-Ribose) Polymerase-1
-
Poly(ADP-ribose) Polymerases
-
Temozolomide