A phase i study of DMS612, a novel bifunctional alkylating agent.

ABSTRACT:

Purpose

DMS612 is a dimethane sulfonate analog with bifunctional alkylating activity and preferential cytotoxicity to human renal cell carcinoma (RCC) in the NCI-60 cell panel. This first-in-human phase I study aimed to determine dose-limiting toxicity (DLT), maximum tolerated dose (MTD), pharmacokinetics (PK), and pharmacodynamics (PD) of DMS612 administered by 10-minute intravenous infusion on days 1, 8, and 15 of an every-28-day schedule.

Experimental design

Patients with advanced solid malignancies were eligible. Enrollment followed a 3+3 design. PKs of DMS612 and metabolites were assessed by mass spectroscopy and PD by γ-H2AX immunofluorescence.

Results

A total of 31 patients, including those with colorectal (11), RCC (4), cervical (2), and urothelial (1) cancers

SUBMITTER: Appleman LJ 

PROVIDER: S-EPMC4755291 | biostudies-literature | 2015 Feb

REPOSITORIES: biostudies-literature