Prodrug TH-302 Plus Radiation Targets Tumor Hypoxia in Patient-Derived Pancreatic Xenografts

Share this content:
(ChemotherapyAdvisor) – The combination of ionizing radiation therapy and the hypoxia-activated drug TH-302 may provide an effective treatment strategy for patients with pancreatic cancer, according to results of a study presented June 19 at the American Association for Cancer Research's Pancreatic Cancer: Progress and Challenges conference, Lake Tahoe, NV.

“The tumor selective hypoxia-activated cytotoxic prodrug TH-302 specifically and selectively targets extreme hypoxia found in solid tumors and is therefore believed to not only increase the treatment response of the primary tumor but also prevent tumor recurrence and metastasis,” noted Ines Lohse, PhD, of Ontario Cancer Institute at the Princess Margaret Hospital, Toronto, Canada. “The clinically validated warhead functions as an alkylator that kills dividing as well as non-dividing tumor cells while designed to be inactive and non-toxic in normal tissues.

The investigators used 7 patient-derived xenograft models to examine the efficacy of TH-302 in pancreatic tumors. Mice received chronic treatment with TH-302 alone, ionizing radiation alone, or both treatments combined: TH-302 treated mice received 3 doses of 50mg/kg TH-302 and mice treated with ionizing radiation received 2Gy on 3 consecutive days.

“TH-302 specifically targeted the hypoxic zone in the xenograft models,” Dr. Lohse reported. “Additionally, TH-302 treatment induced DNA damage in tumor tissue adjacent to the hypoxic zone, which is consistent with the previously demonstrated bystander effect of TH-302.”

In the primary patient-derived xenograft models, treatment with TH-302 in combination with ionizing radiation reduced tumor growth in high and medium hypoxic xenograft models; however, little impact on tumor growth in low or non-hypoxic models was observed.

Response depended on the extent of tumor hypoxia and the tumor growth rate. While showing high treatment efficacy even as a single agent in fast-growing hypoxic models, TH-302 treatment had little effect on tumor growth in a hypoxic model that displayed slow growth rates.

“Our results strongly support the ongoing clinical trials of TH-302,” said Dr. Lohse. “In these trials, TH-302 is being tested in combination with chemotherapy, and one combination has, in fact, been recently reported to prolong progression-free survival in patients with advanced pancreatic cancer. We hope that our data might lead to TH-302 being tested in combination with ionizing radiation as an alternative treatment option for pancreatic cancer.”

Related Resources

You must be a registered member of Cancer Therapy Advisor to post a comment.

Sign Up for Free e-newsletters



Regimen and Drug Listings

GET FULL LISTINGS OF TREATMENT Regimens and Drug INFORMATION

Bone Cancer Regimens Drugs
Brain Cancer Regimens Drugs
Breast Cancer Regimens Drugs
Endocrine Cancer Regimens Drugs
Gastrointestinal Cancer Regimens Drugs
Gynecologic Cancer Regimens Drugs
Head and Neck Cancer Regimens Drugs
Hematologic Cancer Regimens Drugs
Lung Cancer Regimens Drugs
Other Cancers Regimens
Prostate Cancer Regimens Drugs
Rare Cancers Regimens
Renal Cell Carcinoma Regimens Drugs
Skin Cancer Regimens Drugs
Urologic Cancers Regimens Drugs