Palifosfamide (ZIO-201) is in a late Phase II trial in patients with advanced sarcoma, its lead indication. A Phase I/II sarcoma combination trial is now underway.



Sarcomas are cancers of the bone, cartilage, fat, muscle, blood vessels, or other connective or supportive tissues. Soft tissue sarcomas, the expected lead indication of palifosfamide, are relatively rare. On the other hand, in children, soft tissue sarcomas account for approximately 10% of all childhood cancers. The prognosis for patients with adult soft tissue sarcomas depends on several factors including the patient's age, size of the primary tumor, histological grade, and stage of the tumor. Factors associated with a poorer prognosis include age greater than 60 years, tumors larger than five centimeters and high-grade histology. While small, low-grade tumors are usually curable by surgery alone, higher-grade or larger sarcomas are associated with higher local treatment failure rates and increased metastatic (spreading to other areas of the body) potential. Ifosfamide-based chemotherapy is a frequent standard of care for the treatment of metastatic tumors.



Palifosfamide is a proprietary stabilized metabolite of ifosfamide. Ifosfamide has been shown to be effective in high doses in treating testicular cancer, sarcoma and lymphoma. Ifosfamide-based treatment generally represents the standard of care for sarcoma; however, it is not approved by the FDA in this indication. Ifosfamide metabolites include acrolein and chloroacetaldehyde, both highly toxic.

Preclinical studies have shown that palifosfamide has activity in leukemia and solid tumor cancers. These studies also indicate that palifosfamide has a better safety profile than ifosfamide, likely because the toxic metabolites of ifosfamide, acrolein and chloroacetaldehyde are not present in palifosfamide. We believe the administration of palifosfamide may avoid many of the toxicities of ifosfamide without compromising the activity of the drug.