Evofosfamide

Evofosfamide, also known as T-007 or ASTA Z 7654, is a prodrug of cyclophosphamide, an alkylating agent used in chemotherapy. It is a derivative of cyclophosphamide that is designed to be activated by enzymes present in tumor cells. This targeted activation aims to reduce systemic toxicity compared to traditional cyclophosphamide.

The mechanism of action for evofosfamide involves its enzymatic conversion within cancer cells to active metabolites, primarily aldophosphamide and 4-hydroxycyclophosphamide. These metabolites then break down further to produce cytotoxic species, such as phosphoramide mustard. Phosphoramide mustard is responsible for alkylating DNA, leading to cross-linking of DNA strands, DNA damage, and ultimately, apoptosis (programmed cell death) in rapidly dividing cancer cells.

Evofosfamide has been investigated for its potential in treating various cancers, including soft tissue sarcomas and other solid tumors. Clinical trials have explored its efficacy and safety, often in combination with other chemotherapeutic agents. The development of evofosfamide represents an effort to improve the therapeutic index of cyclophosphamide-based chemotherapy by enhancing drug delivery and activation at the tumor site, thereby potentially minimizing side effects on healthy tissues. Further research and clinical evaluation continue to define its role in oncology.