Brain cancer patients with less than a year to live can take hope in a drug considered to be a major break through in the treatment of malignant brain tumors.

Now in its second phase of clinical trial at MUSC and a number of academic medical centers, the unusual therapy essentially forces cancer cells to swallow a poison that is disguised as food. As a result, the poison kills the cancer cells, leaving healthy brain tissue untouched.

Brain tumors are the third leading cause of death from cancer in people ages 15 through 34. Surgeons can usually remove the bulk of the tumor, but they cannot get at finger-like projections of the tumor going deep into brain tissue. “The overall prognosis has been quite grim, with median survival for patients with recurrent tumors being a little less than 12 months,” according to Sunil J. Patel, M.D., an MUSC neurosurgeon.

“The standard of treatment for these tumors is usually surgery and radiation, with some patients responding to chemotherapy. However, invariably all patients have recurrent tumor growth after several months and do not survive.”

The National Institutes of Health (NIH) have conducted tests on a novel experimental therapy. The results were dramatic, with a 50 percent reduction in tumor size in nine of 15 patients and two patients having a complete response to treatment. As a result of these preliminary (Phase I) tests, NIH sponsored a multi center study (Phase II) of the treatment in eight centers, with the MUSC’s Brain Tumor Clinic enrolling the greatest number of patients to date. Twenty-one patients have been treated in the eight institutions (nine of these at MUSC). Of the 21, seven of the patients have had their tumors either disappear or stop growing. Two of these were at MUSC.

The drug (CRM107) is a combination of a highly toxic substance derived from diphtheria toxin and human transferrin, a human protein. “We are able to introduce the compound using a catheter into two small openings in the skull,” explained Patel. The compound is directed into the tumor where the highly active tumor attempts to incorporate the human transferrin as food. But in addition to the human transferrin, the toxin is also incorporated, killing the tumor cells. Since the toxin is only taken up by metabolically active cells, the normal brain cells, which are not metabolically active, are not affected by the toxin.

The drug continues to be under investigation and will require a phase three trial in which doses of the drug will be modified, and tumors will be treated at an earlier stage.

Multi disciplinary study group members

The study is being conducted in the MUSC Brain Tumor Clinic at the university's Hollings Cancer Center. Arthur Frankel, M.D., of the Division of Hematology/Oncology is co-principal investigator, along with Patel, for the study. Frankel is an expert in the design of immunotoxins and has been using this class of drugs for other cancers. Other members of the multi disciplinary group involved in this study are Joseph M. Jenrette III, M.D., Department of Radiation Oncology; Timothy Smith, M.D., Department of Pathology and Laboratory Medicine; Becky Dring, nurse coordinator; and Bonnie Muntz-Pope, research nurse.