Chemotherapy for prostate cancer is still limited to just two drugs, docetaxel (Taxotere) and cabazitaxel (Jevtana). Both of these chemotherapy drugs are taxanes, but they seem to be very different in their mode of action.

A study published online in Clinical Cancer Research, indicates that cabazitaxel might be more effective for some men than docetaxel. Currently, the FDA label requires that a man fail docetaxel prior to being put on cabazitaxel, but it might be more effective for some men to first have cabazitaxel.

Researchers have also found a genomic marker that could help clinicians identify which men might benefit most from cabazitaxel. Men with this marker might benefit from first being exposed to cabazitaxel prior to docetaxel.

“It was surprising to find that cabazitaxel functions differently than docetaxel in killing cancer cells, even though they’re both taxanes,” says the senior author of the paper, Karen Knudsen, Ph.D., Interim Director of the Sidney Kimmel Cancer Center and a professor of cancer biology at the Sidney Kimmel Medical College at Thomas Jefferson University. “It shows that we may not be taking full advantage of this next generation taxane in the clinic.”

Knudsen and colleagues looked at how cabazitaxel worked and concluded that it might be more effective sooner in the treatment protocol. They found that cabazitaxel worked better than docetaxel in human prostate cancer cells lines that were resistant hormone treatment, both in terms of slowing cancer-cell growth and in its ability to kill cancer cells. This might translate to a more effective control of and kill of cancer, which could translate into longer survival.

First author Renée de Leeuw, a postdoctoral researcher in the department of cancer biology at Thomas Jefferson University said that they found that that cabazitaxel and docetaxel have different mechanisms of action and that “This difference in mechanism suggests that we should treat these two drugs less like members of the same family, and more like two distinct therapies that may each have distinct benefits for certain patients.”
To date their research has only been in the lab. Their results confirmed that cabazitaxel was more effective at killing tumor cells than docetaxel.

The research team has also found a molecular marker that would help identify men most likely to benefit from cabazitaxel treatment.

Drs. Kelly and Knudsen are testing their hypothesis in a phase II clinical trial (ABICABAZI NCT02218606) for which they are currently recruiting. Men with metastatic prostate cancer who have not yet been treated with chemotherapy will be given either the second-line hormone therapy abiraterone, or abiraterone in combination with cabazitaxel.

Joel T. Nowak, M.A., M.S.W.