A recent study entitled “Novel Actions of Next-Generation Taxanes Benefit Advanced Stages of Prostate Cancer” published in Clinical Cancer Research showed that cabazitaxel, a new member of the taxane family and FDA approved drug, may be more efficient for treating some prostate cancer patients, a hypothesis now being tested in clinical trials.
In the United States, prostate cancer is the second most common type of cancer in men, with taxanes comprising the only class of chemotherapeutics available to treat this type of cancer. To improve the outcomes of patients with castration-resistant prostate cancer (CRPC) there is an urgent need for more effective therapies and approaches with specific treatments.
For a long time, docetaxel has been the most effective chemotherapy for patients with prostate cancer that were non-responsive to hormone therapy. Cabazitaxel belongs to the second generation of drugs within the taxanes family and was only applied in patients that did not respond to hormone and docetaxel therapy.
Study author Dr. Karen Knudsen explained in a news release that although both drugs belong to the taxanes family, their function is completely different. “It shows that we may not be taking full advantage of this next generation taxane in the clinic,” said Dr. Knudsen.
The team showed that cabazitaxel might be more efficient than docetaxel when used to treat hormone-resistant human prostate cancer cell lines and in earlier phases of treatment. They observed that the drugs had different modes of action: while cabazitaxel had a higher effect on cellular division and regulation of chromatin, docetaxel affected DNA transcription and repair. Moreover, researchers tested both drugs in parallel on slices of tumors collected from patients during radical prostatectomy. The results showed that cabazitaxel was more efficient than docetaxel in eliminating tumor cells. Study author Dr. Renée de Leeuw said these two drugs should be considered as two distinct treatments and with different benefits, depending on the patient profile.
Importantly, the research team showed that tumors not expressing the retinoblastoma (RB) gene had a higher probability of becoming hormone resistant but would respond better to cabazitaxel. Dr. Knudsen explained this gene could be used as a molecular marker to discriminate patients’ response to cabazitaxel treatment.
The Phase II clinical trial (ABICABAZI NCT02218606) evaluating the efficacy of cabazitaxel in patients with metastatic prostate cancer is currently enrolling patients that will be treated either with the second-line hormone therapy abiraterone or abiraterone together with cabazitaxel. Researchers will analyze tumors to assess RB gene expression and to test a possible correlation between low levels of RB and a stronger response to cabazitaxel. This trial is being developed by the Sidney Kimmel Cancer Center and Memorial-Sloan Kettering Cancer Center, and is financially supported by Sanofi.
“The ABICABAZI trial puts these ideas to the test in humans, and if we are correct, has the capacity for the first time to tell us what patients might most benefit from chemotherapy,” concluded Dr. Knudsen.
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