Stabilized IPM

History and Preclinical Development

Palifosfamide (ZIO-201) 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.

Lead indication

Advanced sarcoma will be pursued as the lead indication for palifosfamide. It may be a useful agent that can deliver therapeutic activity in patients with advanced sarcoma with fewer side effects than those associated with ifosfamide.

In the U.S., ifosfamide is regularly included in combination regimens (more than one treatment) for the treatment of sarcomas, testicular cancers, head and neck cancer and some types of lymphomas. We believe in the potential for palifosfamide to replace ifosfamide in any or all of these combinations.

Clinical development plan

A Phase II clinical trial in sarcoma is nearing completion, and a Phase I/II sarcoma combination trial is now underway. For more information regarding treatment centers, please visit our clinical trials page.

About sarcoma

Sarcomas are cancers of the bone, cartilage, fat, muscle, blood vessels, or others connective or supportive tissue. 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.