PARP Inhibitors in Prostate Cancer - Episode 5
Oliver Sartor, MD, discusses the use of rucaparib in treating metastatic prostate cancer.
Matthew Fowler: Focusing again on rucaparib, could you describe the administration and dosing of this drug?
Oliver Sartor, MD: We typically dose it 2 times per day in accordance with the FDA. We’re going to be monitoring it closely for the GI [gastrointestinal] adverse effects, which can be problematic for some patients. It can be associated with nausea and fatigue, and you can have the myelosuppression-type aspects that I’ve noted—particularly anemia, a little thrombocytopenia, a tad of neutropenia. Nevertheless, those parameters must be followed. Then for olaparib, we follow the FDA approval, the 300 mg twice a day, and we monitor these patients carefully. I may have to modulate the dosing, and I may even have to hold dosing if we have problems with anemia, which is probably the No. 1 issue. Then we can reinstitute at the same dose or a lower dose.
If you have a good responding patient, then what you can do is create even a little lower dosing and potentially have good activity. I have a guy right now on 300 mg 1 time per day, and he’s having a great response. He had some significant anemia when he came into it, and he had a PALB2 rather than a BRCA. He’s having a very robust response but just can’t tolerate the 300 mg twice-daily dosing; we had to dose reduce him for anemia.
Matthew Fowler: With PARP inhibitor therapy, what are some of the more common adverse events that you typically see?
Oliver Sartor, MD: I mentioned anemia. That’s the No. 1 issue. Then we have to worry about fatigue, and GI adverse effects. Each of these is potentially problematic; all need to be monitored. Then we can take appropriate steps if needed in an effort to create the best quality of life for that individual patient.
Matthew Fowler: To expand on those steps, how do you mitigate or manage some of these events? When might dose adjustments be necessary?
Oliver Sartor, MD: The most common thing that I’ve had to dose adjust for has been anemia; you’re monitoring the CBC [complete blood count]. By the way, anemia is present in virtually all patients with metastatic CRPC [castration-resistant prostate cancer], so not everybody is going to be affected to the same degree. Yesterday I saw a patient with congestive heart failure. For him, a little anemia is a significant impact on quality of life, whereas I may have another guy who’s 51 years old and fit, and that individual may be able to tolerate much more of an anemia.
It’s not just the number. Remember, you’re treating the patient. The typical way I manage anemia is for either a dose pause or reduction, depending on how significant it is. Then I sometimes use transfusion and continue the dosing. It’s rare, but I’ve done it. I had a relatively older gentleman who comes to mind. He was having a very nice response to the PARP, and if I tried to reduce his dose, his disease would start taking off. I had to give him red blood cell transfusions to keep his dose at the proper level to give him the best response. Everything has to be individualized.
In terms of fatigue, sometimes I’ll use something like methylphenidate, which can be used to alleviate fatigue. That’s 1 thing we can do. I try to make sure that people are getting good sleep at night if feasible. Regarding GI adverse effects, we’re using antinausea-type medications to control that on occasion. It’s rare for patients to have a real problem with adverse events. But in almost all patients, we can work out something that’s a happy medium to be able to get them the dose they need, particularly if they’re responding. If they’re responding nicely, we’re going to work hard to get the right dose for that patient.
Transcript edited for clarity.