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Ziopharm data shows ZIO-201 less likely than other metabolites to cause kidney damage
By Lisa Kerner
Erie, Pa., Feb. 21 - Ziopharm Oncology, Inc. said preclinical data shows that ZIO-201, the active metabolite of ifosfamide, may be less likely to kill normal kidney cells than the other metabolites of both cyclophosphamide and ifosfamide.
Ziopharm believes it may be possible to substitute ZIO-201 for cyclophosphamide and ifosfamide in blood cell and bone marrow transplant conditioning regimens, according to a company news release.
Although cyclophosphamide and ifosfamide are widely used anticancer drugs, their use is associated with kidney, bladder and central nervous system toxicities. These effects are caused by metabolites of cyclophosphamide and ifosfamide, notably chloroacetaldehyde and acrolein, the release stated.
The study of chloroacetaldehyde, acrolein and ZIO-201 on rabbit kidney proximal tubule cells grown in a test tube showed that chloroacetaldehyde and acrolein killed the proximal tubule cells, but ZIO-201 did not.
These data suggest ZIO-201 is less likely to cause irreversible kidney damage than cyclophosphamide and ifosfamide, according to the release. Additionally, the data suggest that it should be possible to give ZIO-201 without giving the bladder-protective agent mesna or intravenous hydration (often needed when high-dose cyclophosphamide and ifosfamide are used).
Mary Taub, Ph.D, of the State University of New York at Buffalo and colleagues presented the preclinical data at the 2006 Bone Marrow Transplant Meetings in Honolulu.
A current phase 1 study of ZIO-201 is ongoing and the maximum tolerated dose has not yet been reached. The company said it expects to begin patient enrollment soon for a phase 1/2 study of ZIO-201 in advanced sarcoma.
New York-based Ziopharm is a biopharmaceutical company engaged in the development and commercialization of in-licensed cancer drugs to address unmet medical needs.
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