Peter Cole Receives Clinical Investigator Award

Peter Cole, MD, assistant professor of pediatrics at UMDNJ-Robert Wood Johnson Medical School, is a recipient of the prestigious 2003 Damon Runyon-Lilly Clinical Investigator Award. The five-year, $995,000 grant will fund Cole’s translational research at The Cancer Institute of New Jersey (CINJ) to increase the cure rate and decrease the toxicity of chemotherapy in children with acute lymphoblastic leukemia (ALL).

ALL is the most common pediatric cancer. The majority of children with ALL can now be cured with chemotherapy, thanks to decades of clinical research. Unfortunately, however, many chemotherapy drugs have negative side effects on children, including neurotoxicity–brain damage that may be permanent.

Methotrexate, a powerful chemotherapy drug that has been widely used to treat ALL, is believed to increase levels of homocysteine in the brain, causing long-term learning disabilities, seizures, and fatigue in pediatric patients. Cole hopes to reduce these side effects using the cough suppressant dextromethorphan (the "DM" found in some over-the-counter cough medications), because he and his colleagues have found that it can block some of the toxic effects of increased homocysteine levels in the brain. In the laboratory, they are studying how chemotherapy causes neurotoxicity and how to predict who will develop it. Clinically, they are testing dextromethorphan in patients to see if it can help prevent or minimize side effects.

In addition, Cole hopes to reduce the toxicity of antileukemia therapy by using aminopterin in the place of methotrexate. Aminopterin, the precursor of methotrexate, came into use 50 years ago, and was the first such chemotherapeutic agent to help children with leukemia go into remission. The drug is not widely used today, but Cole and his mentor, Barton Kamen, MD, PhD, professor of pediatrics and pharmacology at RWJMS and director of pediatric oncology at CINJ, believe it may be more easily tolerated in some patients than methotrexate. “Much lower doses of aminopterin are needed to produce the same effects as methotrexate,” says Cole. “There are also significant disparities between the two in how they are metabolized within cancer cells.”

"We are the first to use aminopterin in place of methotrexate as part of a multi-agent therapy for children with leukemia,” Cole continues. “Our hope is that with lower doses, therapy will be more easily tolerated and produce fewer side effects in children.”

Cole was one of only five recipients to receive this award, which was given by the Damon Runyon Cancer Research Foundation to support young physician-scientists conducting patient-oriented cancer research.