Dr. Cy Stein is a medical oncologist at California’s City of Hope hospital. He routinely advises his fellow doctors to, “Never think about yourself. It’s only about the patient.”
Prostatepedia spoke with him about dealing with the side effects of chemotherapy for prostate cancer. Why did you become a doctor? What was it about medicine that drew you in? What keeps you there?
What are the most common chemotherapy drugs that men with prostate cancer are likely to encounter today?
Dr. Cy Stein: It all depends on what your definition of chemo is, but I take a very narrow definition that I think most of the community would take. There are two chemotherapy drugs that exist for prostate cancer. One of them is called Taxotere (docetaxel). The other is Jevtana (cabazitaxel). I don’t consider drugs like Lupron (leuprolide) to be chemotherapeutic agents. We consider them to be hormonal agents because they act directly on testosterone. Testosterone, as I’m sure everybody knows, is the male sex hormone. In order to get responses in prostate cancer, physicians have to lower the patient’s level of testosterone in their blood. That’s not a chemotherapeutic way of doing it; that’s a hormonal way of doing it.
Similarly, the newer drugs that have come out recently are not chemotherapeutic agents either. I’m referring to Zytiga (abiraterone) and Xtandi (enzalutamide). We call them oral hormonals. Provenge (sipuleucel-T) is a kind of tumor vaccine, so it’s really immunologic oncology. Xofigo (radium 223) is also not a chemotherapeutic agent, so we’re down to two.
What are the differences between the two. When would Taxotere (docetaxel) be used over Jevtana (cabazitaxel)?
Dr. Stein: Taxotere (docetaxel) was first developed in 1995-1996 and has been on the market for a long time. It was originally used in breast cancer and lung cancer as well. Then it was introduced for use in prostate cancer.
There is significant amount of toxicity with Taxotere (docetaxel), although it is a very good drug. It is different from Jevtana (cabazitaxel), even though both of the drugs are formed to the same general class of molecule, which we call taxanes. They both come from, ultimately, the needles of the Pacific Yew tree. Even though the names sound similar, these are different drugs with different toxicity profiles.
The important thing for a patient to remember is that, even though these drugs have side effects, at times we see spectacular responses from both of them. The side effects are manageable and definitely worth the effort for the patient because of the potential for the response that you can get. Taxotere (docetaxel) has more side effects than Jevtana (cabazitaxel). Taxotere (docetaxel) seems to have more toxicity, and most important, the toxicity seems to get worse as patients age. Therefore, I find it extremely difficult, if not impossible, to give Taxotere (docetaxel) to men who are over 80.
What toxicities are we talking about?
Dr. Stein: For Taxotere (docetaxel), the major dose-liming toxicity is fatigue. People are not going to feel anything on the day that they get the Taxotere (docetaxel). The day after, they’re going to feel pretty tired, and most men will want to just stay in bed. Their partners don’t particularly like that, but it’s probably best to leave them in bed because they’re not going to be very functional for a day or more on Taxotere (docetaxel).
It’s not uncommon for a man to say, “For three days after I get this drug, I’m very wiped out.” I’ve even heard them say, “Five to seven days after I get this drug, I feel very wiped out.” Then the men will get better, and eventually they will come back for their next cycle, and we’ll do it all over again. It doesn’t happen quite so much with Jevtana (cabazitaxel) because it is a little easier on the fatigue.
In terms of other side effects, one of the side effects that Taxotere (docetaxel) has, only in about 10% of cases, is febrile neutropenia. That is the white blood cell count goes down seven to nine days after getting the chemotherapeutic drugs and leads to an infection. The patient will have a fever of 100.4 or greater, and the febrile neutropenia requires antibiotics. With Jevtana (cabazitaxel), the incidence of febrile neutropenia is much, much higher. What I do is I make sure that all of my patients have Neulasta (pegfilgrastim) applied before they get the chemotherapy, to prevent their white count from going down.
There are some patients who may not need Neulasta (pegfilgrastim), but I prefer to sleep calmly at night. I don’t want to worry about a patient getting febrile neutropenia on Jevtana (cabazitaxel), so I treat every one of my patients with Neulasta (pegfilgrastim).
In terms of other toxicities, many men say that Taxotere (docetaxel) also causes food to taste like cardboard. Their hair will certainly thin, but it probably won’t all fall out. They may get tearing of the eyes. They may get changes in their nails such as brown bands that horizontally cross the nails. These disappear after discontinuation of treatment. They can also, potentially, get a little bit of fluid in their lungs, although in my experience that hasn’t been a clinical problem. They can also, potentially, develop neuropathy.
It sounds rough, and for some men it is, but a lot of men go through it very well. They can have a tremendous response. I’ve seen any number of individuals have responses of 75% and even 90% in their PSA. These are the kind of individuals who live a great deal longer than if they didn’t respond.
Jevtana (cabazitaxel) is a very similar story, except the fatigue is much less. The neuropathy is significantly less, although I have seen patients with neuropathy on Jevtana (cabazitaxel). The nail banding does not happen. The poor taste doesn’t happen. The hair loss is greatly reduced. Fatigue is also significantly reduced, but there is still fatigue in some patients.
Because the toxicity profile is better with Jevtana (cabazitaxel), I don’t hesitate giving this drug to patients who are over 80 years old. In my opinion, they seem to tolerate it better. I had a patient who was 90 years old and of sound mind and body. He didn’t have much of a choice; he had two sons who were doctors. We talked it over and he said, “I want the drug.” He got the drug, and I started him with a much lower dose than the full recommended dose. I titrated him up to tolerability, and he received 13 consecutive cycles of Jevtana (cabazitaxel). All his pain went away, and he lived an extra year.
Jevtana (cabazitaxel) has a lower dosage option that has just been approved. What has been the impact for your prostate cancer patients?
Dr. Stein: I use two doses of Jevtana (cabazitaxel): 25 mg/m. and 20 mg/ m.. The overall survival with both doses is identical, but at 25 mg/m., the PSA is more affected as opposed to the 20 mg/m.. In other words, you have more PSA decline on the 25 mg/m. than you have on the 20 mg/ m.. Of course, you have less toxicity on the 20 mg/m.. For those men who really follow their PSAs very closely, I might, all other things considered, recommend the 25 mg/m.. For most men, I think the 20 mg/m. is just fine. For Taxotere (docetaxel), the full dose is 75 mg/m.. There’s little evidence that you lose much in the way of efficacy if you go to 50 mg/m. to avoid toxicity, and I’ll do that frequently.
Is there anything men can do to prepare themselves for these side effects?
Dr. Stein: Aside from communicating with their doctors and taking Claritin if you’re receiving Neulasta (pegfilgrastim), I’m not sure there is anything you can do.
Is there anything else you’d like patients to know about chemotherapy for prostate cancer?
Dr. Stein: These are very realistic options for patients. Men can tolerate Taxotere (docetaxel) for maybe six to eight cycles. It’s hard for men to get more. With Jevtana (cabazitaxel) it’s unbelievable how much people can get because the toxicity is less. I know of a man who received 55 continuous cycles of Jevtana (cabazitaxel) and did extremely well. My own personal record is 33 cycles. In one of those cases, the patient had a 99% response in his PSA; he lived three extra years. He did extremely well. I had another man who also got 33 cycles. His PSA was roughly 50 to 70 and it stayed that way for 33 cycles before he started to progress. I have seen quite a few remarkable responses.