Grant for Human Trials of Cancer Treatment

V Foundation grant will yield testing of Valter Longo’s chemotherapy shield by asking cancer patients to fast for two days before treatment.
By Athan Bezaitis
Investigators Amy Lee, Valter Longo, David Quinn and Tanya Dorff

USC researchers Valter Longo and David Quinn have received a three-year, $600,000 grant from the V Foundation for Cancer Research, co-founded by the late basketball coach Jim Valvano, to conduct human trials on a promising new treatment for cancer.

Based on Longo’s breakthrough research published last March in PNAS Early Edition, which found that fasting for two days protected healthy cells against chemotherapy in both mice and human cells in test tubes, the highly anticipated experimental method will be tested on cancer patients beginning in early November.

Longo, associate professor at the USC Davis School of Gerontology and USC College, discovered that mice given a high dose of chemotherapy after 48 hours without food continued to thrive, while the same dose killed half the mice fed normal diets and caused lasting weight and energy loss in the remaining survivors.

In human cells, test tube experiments revealed a greater resistance to chemotherapy for healthy cells after a short period of fasting while cancerous cells were reduced.

“We will test this approach with different carcinomas and chemotherapy drugs in mice and also propose parallel clinical human studies to see for the first time whether short-term fasting can protect patients against the side effects of chemotherapy,” Longo said.

For many years, defending against the debilitating effects of chemo has been a top goal of cancer research with treatment focused primarily upon cancerous cells. Longo’s method proposes a joint attack that targets both cancerous cells and protects healthy cells.

“Protecting all healthy cells at once is the primary focus in the anti-aging field,” Longo said.

If it is effective, the chemotherapy shield would allow oncologists to potentially control cancers, making chemotherapy less toxic to the rest of the body.

“Proposed studies have the potential to provide data that could have a broad impact on cancer treatment worldwide and across tumor types in the near future,” Longo said. “The resulting data will also serve as an impetus for the development of drugs that mimic the effects of fasting.”

Starved cells go into survival mode, Longo said, characterized by extreme resistance to stresses. In essence, these healthy cells are waiting out the lean period, much like hibernating animals. But tumors respond differently to starvation; they do not stop growing, nor do they hibernate because their genetic pathways are stuck in an “on” mode.

Longo realized that the starvation response might differentiate normal and cancer cells by their increased stress resistance and that healthy cells might withstand much more chemotherapy than cancer cells.

“This could have applicability in maybe a majority of patients,” said Quinn, practicing oncologist and medical director of USC Norris Hospital and Clinics.

Cancers of the bladder and lung will be tested first.

The initial stage of the trial will determine safety and feasibility of fasting. Researchers will first examine whether a 24-hour fast is safe. If so, they will test a 48-hour fast, and on up to 72 hours if it is deemed feasible.

“The second stage of the trial will randomly assign patients to eat normally before chemo or to fast for the amount of time we select based on the experience in the first stage,” said Tanya Dorff, assistant professor of clinical medicine at USC Norris Cancer Center and co-principal investigator of the study.

Given three years of funding for trials, comprehensive results should become available much earlier.

“We will certainly see results within two years, allowing time to accrue cohorts in both stages of the trial, and may have an earlier glimpse if enrollment is rapid,” Dorff said.

The plan is not to give higher than standard doses of chemotherapy to cancer patients, rather patients will get the same treatment as if they did not participate in the clinical trial, Dorff said.

“The goal is to see a reduction in the frequent toxicities that we currently see with this standard regimen instead of 71 percent having grade three or four neutropenia (low white blood cells) we are hoping to see only 36 percent experience it. Instead of 57 percent grade three or four thrombocytopenia (low blood platelets), we are hoping to see 29 percent, etc. All standard chemo side effects will be assessed in fasting patients and controls to look for a difference.”

The potential to make an immediate difference is what attracted the attention of the V Foundation for Cancer Research, which began as the dream of Jim Valvano, the former North Carolina State basketball coach and award-winning broadcaster, who died of cancer in 1993.

Over the past 14 years, the organization has raised more than $70 million and awarded cancer research grants in 37 states and the District of Columbia.

“The scientific advisory board of The V Foundation selects the most promising researchers to make advances in cancer research,” said Nick Valvano, CEO of The V Foundation.

Grants such as the one won by Longo and Quinn in translational clinical research facilitate the evolution of projects from the laboratory to the clinic.

“Dr. Longo shows interesting potential with his research on the effects of fasting to protect healthy cells from toxicity,” Valvano said. “This novel approach may ease the effects of chemotherapy and make patients more comfortable through the treatment process.”

Amy Lee, professor of biochemistry and molecular biology at the Keck School of Medicine of USC, is also a co-principal investigator.

Carl Marziali contributed to this article.