Evofosfamide sensitizes esophageal carcinomas to radiation without increasing normal tissue toxicity.

ABSTRACT:

Background and purpose

Esophageal cancer incidence is increasing and is rarely curable. Hypoxic tumor areas cause resistance to conventional therapies, making them susceptible for treatment with hypoxia-activated prodrugs (HAPs). We investigated in vivo whether the HAP evofosfamide (TH-302) could increase the therapeutic ratio by sensitizing esophageal carcinomas to radiotherapy without increasing normal tissue toxicity.

Materials and methods

To assess therapeutic efficacy, growth of xenografted esophageal squamous cell (OE21) or adeno (OE19) carcinomas was monitored after treatment with TH-302 (50 mg/kg, QD5) and irradiation (sham or 10 Gy). Short- and long-term toxicity was assessed in a gut mucosa and lung fibrosis irradiation model, sensitive to acute and late radiation

SUBMITTER: Spiegelberg L 

PROVIDER: S-EPMC6913516 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature