Sen. Edward Kennedy's brain cancer has made the world more aware of malignant glioma. While prognosis for brain-cancer patients is grim, new vaccines and drugs in the pipeline offer extended quality of life and hope of a cure.
Only about half the patients who are diagnosed with malignant gliomas live one year. About 25 percent survive beyond two years. There's no getting around it; the prognosis for this type of cancer is grim. However, innovative treatment options, including vaccines and new drugs in the pipeline, are providing doctors with new tools and patients and their families with the promise of extended quality of life and hope for a cure.
The World Health Organization reports that when standard local treatments are used, the cure rate for patients with glioblastoma (GBM) is very low. According to the National Cancer Institute, standard treatment includes surgical resection, radiation therapy and chemotherapy. However, in some cases, surgery can be too risky and not a viable option, as when a tumor invades surrounding healthy brain tissue.
"The treatment options for glioblastomas have expanded significantly over the past 10 years," said Julia Hammond, PharmD, oncology clinical coordinator at Duke University Hospital in Durham, NC. Hammond told Drug Topics that several of the chemotherapy options that were approved in the mid- to late 1990's have proven effective and several combinations are currently in use or under investigation.
Howard Coleman, MD, PhD, assistant professor, Department of Neuro-Oncology at The University of Texas M.D. Anderson Cancer Center in Houston said U.S. Food and Drug Asministration (FDA)-approved drugs for newly diagnosed glioblastoma include temozolomide (Temodar) and Gliadel (biodegradable wafers that deliver BCNU directly into the surgical cavity at the time of resection).
"Temozolmide has become the most common first-line chemotherapy used for glioblastoma and lower-grade gliomas," Coleman said. "Use of Gliadel is variable, often related to practice patterns at a particular institutions." He added that older chemotherapy agents that are sometimes used to treat glioblastoma and other gliomas (usually as second-line or later therapy) include CPT-11 (irinotecan), procarbazine, CCNU, vincristine (PCV), carboplatin and carmustine (BCNU).
"If I had to sum up the current status, the standard therapy is radiation therapy combined with temozolomide for newly diagnosed glioblastoma, and the most common nonprotocol therapy for recurrent glioblastoma is CPT-11 and Avastin, with the general class of anti-angiogenic agents figuring prominently in many current and upcoming clinical trials," Coleman said. He added that many of the anti-angiogenic agents share the side effect of hypertension and thrombosis/bleeding risk, while the tyrosine kinase inhibitors can produce rash or hand-foot syndrome.
Vaccine trials are taking place at several sites across the United States, including Duke and MD Anderson Cancer Center in Houston.
Coleman said that CDX110, the EGFRvIII peptide vaccine that was developed at Duke and MD Anderson, is currently in a Phase III multicenter trial. Other centers, including UCLA, are conducting trials of a dendritic cell vaccine made from the patient's tumor at the time of surgery. Additional peptide vaccines are in development at a number of centers around the country.
On the horizon
Duke's Hammond said that clinical trials continue to explore the effectiveness of novel agents in the management of GBMs. Others are looking at combinations of chemotherapy and radiation therapy as well as combinations of chemotherapies in new regimens. She noted that there are also studies evaluating many of the available "targeted therapies" in patients with brain tumors.
Additional therapeutic targets/agents that are being tested in early phase trials include PI3-kinase inhibitors, Akt inhibitors, FGF inhibitors and HGF inhibitors, Coleman said.