Brain Tumor Therapy May Prolong Life By John Cramer Scientists at Johns Hopkins report that a brain tumor treatment which delivers an anti-cancer drug in a time-release fashion from surgically implanted biodegradable polymer discs has proved its value in prolonging the lives of some dying patients. Results of the study on 222 patients at 27 hospitals are reported in the April 22 issue of The Lancet. "The treatment should greatly change conventional therapy for brain tumors and possibly cancers in other organs," says study author Henry Brem, director of neurosurgical oncology at the Medical Institutions. "Although the trials were conducted with patients with advanced tumors with this study, we can say the new treatment may be a more logical part of initial therapy," Dr. Brem added. "This will be relevant for practical treatment immediately, not 20 years from now, and it's exciting because it opens the door for further uses." There are an estimated 20,000 brain cancer surgeries performed each year in the United States. Dr. Brem anticipates that the biodegradable polymer disc could be the treatment of choice for as many as 40 percent of those patients within three years after FDA marketing approval. The new polymer-drug combination system is currently under FDA review. Among the patients with brain tumors, study results showed median survival rates of 31 weeks for 110 patients receiving carmustine (BCNU) saturated polymers compared to 23 weeks for 112 patients getting placebo polymers, a 34 percent improvement in survival time. For patients with glioblastoma multiforme, the most common and severe tumor, results were even better, Dr. Brem said. Six-month survival was 50 percent higher in patients receiving the BCNU-polymers than in those treated with placebo polymers. Moreover, the BCNU-polymers produced no significant side effects, and the patients' quality of life was good, Dr. Brem said. The main targets of the polymer technique are malignant gliomas, the most common form of malignant brain tumor, which are highly lethal and conventionally treated with surgery followed by radiation therapy and/or chemotherapy. Other brain diseases, as well as cancers needing central nervous system treatment, may in the future be treated by these controlled-delivery polymers. The Lancet report confirms preliminary findings that Dr. Brem presented in 1994 describing earlier controlled trials of the polymer wafers. For 10 years, Dr. Brem has been investigating this new way of delivering drugs against brain tumors as an alternative to conventional chemotherapy, in which the whole body or a region is exposed to large amounts of drugs, causing severe side effects. Moreover, only trace amounts reach the brain in conventional treatment because of the blood-brain barrier, which protects the brain from chemical fluctuations by restricting the entry of molecules, including drugs aimed at brain tumors. The new study evaluated 222 patients with recurrent malignant brain tumors at 27 hospitals which make up the Polymer-Brain Treatment Group. Patients were randomly assigned to receive the dime-size discs with or without BCNU. After the tumors were surgically removed, the discs were put into the resulting cavity to deliver small amounts of medication to the tumor bed in a sustained-release fashion to destroy any remaining cancer cells. "This is the first full demonstration that localized drug therapy [vs. traditional chemotherapy] is safe and effective in prolonging life in these patients with brain tumors," Dr. Brem said. "It's proof that controlled-release polymers work." Researchers at Hopkins continue to look for the most effective drugs for use in the polymers, which dissolve at a controllable rate. Dr. Brem has published four articles in the past year on animal research with promising results against brain cancer with the drugs taxol, the anti-angiogenic antibiotic minocycline, 4-hydroperoxycyclophosphamide (4HC) and camptothecin. These drugs were ineffective when given systemically by traditional injection, but were highly effective when delivered with polymers directly to the brain. Thus, the polymers may allow these drugs to be used for treating brain tumors. Early safety testing in people may start in the fall at Hopkins. The five-year Lancet study was funded by grants from the National Cancer Institute and Guilford Pharmaceuticals, Inc., which is developing the polymers for therapeutic applications. The company, based in Baltimore, plans to file an application with the Food and Drug Administration for marketing approval within the next year. The study was based on a collaborative effort between Hopkins and the Massachusetts Institute of Technology, where a biodegradable polymer that can release drugs was invented.
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