TH-302 in combination with doxorubicin for locally advanced or metastatic, unresectable soft tissue sarcoma – first line
TH-302 in combination with doxorubicin is intended for the treatment of unresectable locally advanced or metastatic soft tissue sarcoma. If licensed, TH-302 will offer an additional treatment option for this patient group. TH-302 is a cytotoxic, hypoxia-activated pro-drug(HAP)/DNA cross-linking agent consisting of a toxic portion and an attached trigger molecule. The toxic portion is kept inactive by the trigger molecule until the prodrug is in a hypoxic environment such as parts of tumours with poor blood supply. The low oxygen concentration stimulates activation of the drug and the killing of nearby cells. TH-302 is used in combination with doxorubicin, a cytotoxic drug with poor tissue penetration that targets the tumour regions located in close proximity to tumour blood vessels. This combination may enable the targeting of both the normoxic and hypoxic tumour regions.
Sarcomas are a rare diverse group of cancers, broadly divided into those arising in bone and those arising in soft tissue. Soft tissue sarcomas develop in the supporting and connective tissues anywhere in the body. Frequently they occur in the limbs (mostly the legs), which account for around half of diagnosed cases, but are also commonly seen in the trunk, abdomen and pelvis. Soft tissue sarcomas recur after initial treatment in around 50% of patients; in some these will be localised to the origin site however many will have metastasised. The latest data available indicates that 2,740 new cases of soft tissue sarcomas were diagnosed in the UK in 2010. It is estimated that the incidence of advanced disease is approximately 550 cases per year in England with approximately 79% of these patients eligible to receive first line chemotherapy.
Soft tissue sarcomas are usually treated with a combination of surgery, chemotherapy and radiotherapy. Pharmacological treatment options for advanced and/or metastatic disease include anthracyclines, alkylating agents or other neoplastic agents. TH-302 in combination with doxorubicin for unresectable locally advanced or metastatic soft tissue sarcoma is currently in phase III clinical trials comparing its effect on overall survival against doxorubicin alone. This trial is expected to complete in April 2015.