Preliminary studies with a new hypoxia-selective cytotoxin, KS119W, in vitro and in vivo.

Agents with selective toxicity to hypoxic cells have shown promise as adjuncts to radiotherapy. Our previous studies showed that the bioreductive alkylating agent KS119 had an extremely large differential toxicity to severely hypoxic and aerobic cells in cell culture, and was effective in killing the hypoxic cells of EMT6 mouse mammary tumors in vivo. However, the limited solubility of that compound precluded its development as an anticancer drug.

Preclinical evaluation of Laromustine for use in combination with radiation therapy in the treatment of solid tumors.

Purpose: These studies explored questions related to the potential use of Laromustine in the treatment of solid tumors and in combination with radiotherapy.

Materials And Methods: The studies used mouse EMT6 cells (both parental and transfected with genes for O(6)-alkylguanine-DNA transferase [AGT]), repair-deficient human Fanconi Anemia C and Chinese hamster VC8 (BRCA2(-/-)) cells and corresponding control cells, and EMT6 tumors in mice assayed using cell survival and tumor growth assays.

Results: Hypoxia during Laromustine treatment did not protect EMT6 cells or human fibroblasts from this agent.