Dr. William Oh, of the Mount Sinai Medical Center and the Icahn School of Medicine at Mount Sinai in New York City, is a medical oncologist and expert in the management of prostate, renal, bladder, and testicular cancers.
Prostatepedia spoke with him about the role chemotherapy plays in prostate cancer treatment strategies.
What types of chemotherapy are available to prostate cancer patients today?
Dr. Oh: In many ways and for many patients, chemotherapy has a negative reputation. People tend to lump all chemotherapy drugs together, but it’s very important to remember that there are hundreds of kinds of chemotherapy. The word chemotherapy really just means chemical therapy for cancer, but that’s not the same thing for everyone.
There are two major chemotherapy agents approved and commonly used in prostate cancer: Taxotere (docetaxel) and Jevtana (cabazitaxel). When Taxotere (docetaxel) was first approved in 2004, it was really an important milestone because up until that point, there were no drugs of any kind that were proven to improve survival in metastatic prostate cancer.
Taxotere (docetaxel) showed that it could be done. Then it took many years of research and clinical trials to get to the next set of drugs that improved survival, especially in castrate-resistant prostate cancer. These include drugs like Zytiga (abiraterone), Xtandi (enzalutamide), Provenge (sipuleucel-T), and Xofigo (radium 223). Since 2004 with the approval of Taxotere (docetaxel), we still think improving survival is the most important goal for patients with advanced prostate cancer. As an oncologist, I felt the survival improvement is— for most patients–worth the side effects patients may have.
This is a critical point, because many people think that chemotherapy has terrible side effects and doesn’t do anything of value. That is not a fair stereotype. While it does have side effects, and it doesn’t always work, in many ways, chemotherapy has great value for our patients in terms of improving both their survival and their quality of life.
The perception is definitely that the side effects of chemotherapy can be terrible, so how might chemotherapy improve quality of life?
Dr. Oh: When we first started giving chemotherapy for metastatic disease (and still today), patients were often very symptomatic. They had a very short expected lifespan, and they were in pain. They were weak. They couldn’t walk. They would have a lot of side effects from cancer. The way that drugs like chemotherapy can boost quality of life is that, by shrinking the cancer—by directly killing cancer cells, we can make patients feel better. If they have fatigue or some hair loss from chemotherapy, that wasn’t something they wanted, but they could be in a much worse state from the cancer itself. They were really suffering from it.
In balance, the chemotherapy was able to make them feel better by reducing their pain medication requirements and by improving their functionality and their appetite. We often see that. When chemotherapy works—and it’s not always—it can really shift a person’s quality of life, and it also improves their duration of life. These are the two critical factors for any cancer drug.
When is a patient likely to encounter Taxotere (docetaxel) and Jevtana (cabazitaxel)? Why would your doctor choose one over the other?
Dr. Oh: When docetaxel was first approved, it was approved for metastatic castrate-resistant prostate cancer (CRPC).
In that state, it had a relatively modest survival benefit on average. But for individual patients, it could have a dramatic benefit. We always thought, why wait till the patients develop CRPC? If we use it earlier, would it have a greater impact?
In 2015, the CHAARTED and STAMPEDE studies showed that early use of Taxotere (docetaxel) chemotherapy in men with newly diagnosed metastatic disease could have a very profound improvement on survival. In other words, rather than waiting for the cancers to become resistant to hormone treatments, if you used hormones with chemotherapy right up front—six cycles of Taxotere (docetaxel)—you could have a more dramatic improvement in overall survival.
That changed the standard of care for how we use Taxotere (docetaxel) chemotherapy. Now it’s an optionfor patients when they’re newly diagnosed with metastatic disease. Jevtana (cabazitaxel) was approved in 2010 based on the TROPIC study in patients who had already received first-line Taxotere (docetaxel). Jevtana (cabazitaxel) is currently a second-line chemotherapy agent. It does have a different set of side effects compared to Taxotere (docetaxel). For example, patients are less likely to lose their hair. It is in the same drug class as Taxotere (docetaxel); in other words, it’s a taxane chemotherapy and works by inhibiting the microtubules that allow cancer cells to grow rapidly. Jevtana (cabazitaxel) was approved because, even in patients who had already received Taxotere (docetaxel), Jevtana (cabazitaxel) improves survival and may be an important second chemotherapy for patients to receive after they’ve already received Taxotere (docetaxel).
Are these drugs ever used in combination with something else?
Dr. Oh: Generally, chemotherapy is not used in combination with other drugs because usually these drugs are given in sequence. Whether this is the correct way to do it or not is not 100 percent clear. There are ongoing research studies to see if they can be combined safely rather than given in sequence because they may have an additive or synergistic benefit if you combine, for example, a chemotherapy drug with an androgen-receptor targeted therapy or with a bone-targeted therapy.
As in Erleada (apalutamide) or Xtandi (enzalutamide)?
Dr. Oh: Exactly.
What should men know if they’ve been prescribed one of these drugs?
Dr. Oh: Try not to have an uninformed ‘gut reaction’ to chemotherapy, especially if you think automatically it’s not the right treatment. We know that chemotherapy may be less targeted than other drugs, but cancer cells are tricky and they often learn how to mutate and change. Chemotherapy can knock out many different kinds of cancer cells. That may be one of its advantages. It works differently than androgen-receptor therapy, immunotherapy, and bone therapy. Men should understand that chemotherapy is a very important option, especially when the cancer has become more aggressive.