The drug cabazitaxel improved the survival of some patients with advanced prostate cancer compared with those who received standard chemotherapy, according to results from a randomized phase III clinical trial presented March 5, 2010, at the Genitourinary Cancers Symposium in San Francisco. Although the benefit was modest (several months), there currently are no effective treatments for patients with this form of the disease, called metastatic castration-resistant, or hormone-refractory, prostate cancer. These results led to FDA approval of cabazitaxel on June 17, 2010, for men with this type of prostate cancer.
“This is the first positive study of its kind,” said Nicholas Vogelzang, M.D., chair and medical director of the Developmental Therapeutics Committee of the company US Oncology, who moderated a press briefing on March 3 ahead of the symposium. Cabazitaxel should clearly be considered now as an alternative for men in whom standard chemotherapy has failed, he added.
The international TROPIC (Treatment of Hormone-Refractory Metastatic Prostate Cancer Previously Treated with a Taxotere-Containing Regimen) study included 755 men whose prostate cancers had progressed despite treatment with hormone therapy and subsequent chemotherapy with docetaxel , which is the standard drug used to treat men with advanced disease. The participants were randomly assigned to receive cabazitaxel plus prednisone or another chemotherapy drug, mitoxantrone, also in combination with prednisone.
With a median follow-up of 12.8 months, median overall survival for men in the cabazitaxel group was 15.1 months compared with 12.7 months for patients in the mitoxantrone group. This translates into about a 30 percent reduction in the risk of death, said lead investigator Oliver Sartor, M.D., of the Tulane Cancer Center.
Cabazitaxel—which, like docetaxel, is part of a class of drugs known as taxanes—was designed to be active in cells that develop resistance to docetaxel, which happens in many patients with this disease. The drug appears to elude a mechanism in prostate cancer cells that pumps anticancer drugs out of the cells before they have a chance to be effective, the researchers said.
The improvement in overall survival was consistent across different patient subgroups, such as those stratified by age, race, and certain co-morbidities, Dr. Sartor said. And men treated with cabazitaxel also had improvements in important measures such as length of survival without tumor growth (progression-free survival) and significant tumor shrinkage following treatment (response rate).
In terms of side effects, patients who received cabazitaxel were more likely to experience febrile neutropenia, a high fever associated with significant reductions in white blood cells called neutrophils. So, Dr. Sartor advised, patients treated with cabazitaxel need to be “carefully watched” for this toxicity.
Because there is no well-accepted standard treatment for men whose tumors no longer respond to docetaxel, choosing the treatment with which cabazitaxel would be compared was difficult, Dr. Sartor noted. Mitoxantrone was chosen instead of a placebo because it has some activity in these types of patients, he explained.
“It’s a promising feature that you can treat patients with a taxane-based chemotherapy in a second-line setting and still have a response and reasonable tolerance,” said Daniel George, M.D., an assistant professor of medicine and urologic surgery at the Duke University Comprehensive Cancer Center. And patients who respond well to first-line treatment with docetaxel tend to fare better with second- and third-line therapies, Dr. George added. “So, for those patients this may be even more of an advance.”
The results also further confirm that in patients with advanced prostate cancer, chemotherapy isn’t strictly a last ditch treatment, Dr. George said, but that it “can really extend survival even further than we originally recognized.”
Noting that advances in treating cancer have always been incremental, Dr. Vogelzang said that the results were similar to those from the 2004 study that demonstrated the benefit of docetaxel as treatment for advanced prostate cancer.
The third annual symposium was co-sponsored by the American Society of Clinical Oncology, the American Society for Radiation Oncology, and the Society of Urologic Oncology.