Garry Buettner, PhD

Free Radical and Radiation Biology
Department of Radiation Oncology
The University of Iowa, Iowa City, IA

 image of Dr. Gary Buettner

Abstract: Ascorbate functions as a versatile reducing agent. At pharmacological doses (P-AscH-, [plasma] ≈20 mM), achievable through intravenous delivery, oxidation of AscH- can produce a high flux of H2O2 in tumors. Normal cells/tissues seem not to be affected by an increased flux of H2O2, while exposure to an increased flux of H2O2 is detrimental to many cancer cells. I will address three basic issues for the use of P-AscH- in the treatment of cancer: (1) the oxidation of ascorbate to produce a flux of H2O2; (2) catalase as the first-line defense of cells against an increased flux of H2O2; and (3) potential downstream modulators of the cellular response to this oxidative challenge. Our laboratory is quantitatively addressing these three aspects of the potential use of P-AscH- to treat cancer. I will show how data from experiments that address these issues are used to guide clinical trials.

The encouraging data from our basic science efforts have underpinned six clinical trials on the use of P-AscH- as an adjuvant to the standard of care at The University of Iowa; 1 completed (Phase 1, pancreatic cancer with gemcitabine); 1 terminated (Phase 2, pancreatic cancer with gemcitabine); 2 active, but recruiting is finished (Phase 1, pancreatic cancer with gemcitabine and radiation; Phase 1, glioblastoma multiforme, temozolomide and radiation); 2 active and recruiting (Phase 2, Non-Small-Cell Lung Cancer Paclitaxel, Carboplatin); Phase 2, glioblastoma multiforme, temozolomide and radiation). An overview of current results will be presented.

Conclusions: From our basic science results, P-AscH- may be and effective adjuvant for some standard of care therapies; P-AscH- is safe as an adjuvant with the chemotherapeutic agents we have tested as well as with radiation; adverse events are minimal and mild; there are suggestions of efficacy.