PARP Inhibitors in Ovarian Cancer: Safety Profile

Transcript:

Bradley J. Monk, MD, FACOG, FACS: Let’s talk about the toxicities of PARP inhibitors. They can be sort of allocated into 3 buckets: GI [gastrointestinal]; and then second, fatigue; and third, bone marrow. Let’s talk about the GI toxicities. Brian, how do you counsel a patient about the GI toxicity when you begin a PARP [poly (ADP ribose) polymerase] inhibitor?

Brian M. Slomovitz, MD: That’s a great question. When I begin the PARP inhibitors, I will talk to the patient about those 3 general classes of adverse effects that you described. I talk to them about the potential for the GI toxicities, and if necessary, I either prophylax them with an antinausea or upper-GI prophylaxis or start it pretty early if we’re seeing some of the symptoms.

Bradley J. Monk, MD, FACOG, FACS: Yeah. I like to put everyone on an anti-acid, proton pump inhibitor, H₂ blocker. And then probably react with an antiemetic. What do you think, Katie? Use a reactive antiemetic or a proactive antiemetic?

Kathleen N. Moore, MD: I think you can do either, as long as you set expectations well with your patient. I tend to send them home with a prescription for an antiemetic, and I use it for the first couple of months just so they don’t set that kind of brain cycle of, “I’m going to be nauseated with this drug.” And then I try and wean it off because no one wants your patient on Zofran for 2 years.

But I also think your method completely makes sense, as long as you have a patient whose expectations have been set and who has good access to your office nurses, and you can have someone react to her complaints right away. That helps the patient stay on therapy.

Bradley J. Monk, MD, FACOG, FACS: Right. And again, it’s not just nausea; it’s also diarrhea. I think we kind of agree that Lomotil is the prophylactic for diarrhea. But what’s your go-to prophylactic for nausea in the setting of a PARP inhibitor?

Elena S. Ratner, MD: We use a lot of medical marijuana in this setting. I set my patients up by saying, “You know, nausea could happen.” I send them home with Zofran just as you do. We give them some Pepcid—or some sort of a blocker—but we routinely prescribe and advocate for marijuana.

Bradley J. Monk, MD, FACOG, FACS: That’s interesting and a very, very valuable perspective. I used to use ondansetron. I had trouble with constipation.

Kathleen N. Moore, MD: Yes.

Bradley J. Monk, MD, FACOG, FACS: And then I used to use Compazine, but that was too toxic. We’ve been using olanzapine 5 [mg]. Have you ever tried that?

Kathleen N. Moore, MD: We talked about this just 2 weeks ago, so I haven’t tried it yet. But I’m going to.

Bradley J. Monk, MD, FACOG, FACS: OK.

Kathleen N. Moore, MD: I like the idea. I think it’s better because you do get headaches and constipation with Zofran, but you don’t get the prochlorperazine kind of sedation and adverse effects.

Bradley J. Monk, MD, FACOG, FACS: Yeah. So there are 3 general toxicities to all PARP inhibitors as a class: GI, which includes nausea and diarrhea; bone marrow; and fatigue. Within the bone marrow there used to be a lot of discussion about thrombocytopenia. With the personalized dosing of niraparib, they’re more similar than different. As a result of that, anemia evolved as the most common sort of bone marrow suppression. How do you handle anemia in the setting of PARP inhibitors?

Elena S. Ratner, MD: Anemia is so much easier to handle than thrombocytopenia, and it’s also so wonderful to even talk about this now. We saw thrombocytopenia originally with niraparib, and this is just an example as to how we evolve, right? Everything evolves. We saw the problem and we figured out the solution, and now it’s no longer an issue. Now we’re talking about anemia being the biggest problem, which is wonderful.

I find anemia to be much, much less difficult than thrombocytopenia because you can just transfuse. We have very rigid protocols for checking complete blood counts, and we are able to catch it early.

Bradley J. Monk, MD, FACOG, FACS: We used to say that maybe there was a folate deficiency in the patients who were anemic. I said that, and the next thing I knew every one of the patients were on a folate-containing multivitamin. So that doesn’t work anymore. And I like transfusions because they’re cheap, they always work, and they’re safe. I get it that there’s a point where you just can’t be so transfusion dependent. Do you guys ever use EPO [erythropoietin]?

Kathleen N. Moore, MD: Not in this setting. I transfuse. If they need a transfusion every 6 months, I’m going to keep them on the same dose and keep treating. If you have someone who is dropping, dropping, dropping, then I’m going to dose modify. But I’m probably not going to put them on EPO [erythropoietin], to be honest.

Bradley J. Monk, MD, FACOG, FACS: You know, it also is important to mention that when these sorts of toxicities occur—GI or anemia—if you wanted to, you could stop, recover, and dose reduce. So that’s always an option. And certainly in the setting of olaparib, because they’re on treatment for so long in the front line, if you recall about 45% of the patients could maintain the full dosage of 300 mg twice daily. But of the 55% who needed dose interruptions, only about 28% needed dose reductions. So there was an opportunity to stop, recover, and with more sort of intervention, keep on the same dose. But some patients needed to be dose reduced, and the dose reductions frequently resolved the toxicity.

So, fatigue. Is it related to anemia? I always say the most common cause of fatigue in Arizona is dehydration. And I always say the reason for your fatigue is because you’re sleep deprived. I know the reason that I’m fatigued is not because I’m malnourished, because I love to eat. So what’s your approach to fatigue in PARP inhibition?

Elena S. Ratner, MD: Marijuana.

Bradley J. Monk, MD, FACOG, FACS: It’s not crazy, because you get some sleep and you become calm.

Elena S. Ratner, MD: And you drink more.

Bradley J. Monk, MD, FACOG, FACS: Sleep deprivation is a real challenge in our patients, and we have a sleep hygiene sort of approach. What’s your approach to fatigue?

Kathleen N. Moore, MD: You have to work up other etiologies, so that’s the important thing to remember. Make sure they’re not anemic. Make sure they don’t have low folate or low B₁₂ or thyroid. We miss thyroid a ton in our patients. We’re just not thinking about it. I don’t know about your practice, but in Oklahoma we’re their primary care. They don’t often have another doctor. So if you’re not checking their thyroid, no one is. And so we find a lot of hypothyroidism. And you’ve ruled all that out. It’s maintaining activity. So we have a lot of interventions with physical therapy. We tell patients 150 minutes of walking a week and they can divide it up, so that’s a goal. There’s some herbal marijuana. Although it is legal now, we can’t write for it yet.

Bradley J. Monk, MD, FACOG, FACS: Why can’t you write for it?

Kathleen N. Moore, MD: Because there are rules, and they haven’t figured out the rules for us writing about it yet, like writing a script. So it’s legal, but I can’t write the script. I would like to keep my job. But my patients are ready for it, for sure.

Bradley J. Monk, MD, FACOG, FACS: So we have a whole process for medical marijuana because it’s evidence based.

Elena S. Ratner, MD: Of course.

Bradley J. Monk, MD, FACOG, FACS: And it’s safe, generally. Brian, how do you deal with fatigue?

Brian M. Slomovitz, MD: I’m in Miami. It’s hot out. So it’s important to be making sure that they’re well hydrated. They should be walking around with a water bottle. You know, patients aren’t having 3 meals a day. They should be having 6 small meals a day because they’re not hungry for a big meal. Getting their rest. You know, I think underlying depression is a big component of fatigue. We have a lot of support groups in our hospital that are working with patients. We have patients teaching other patients. And we have social workers and psychologists and psychiatrists. So looking for the underlying cause of fatigue and pushing through it, really.

Transcript Edited for Clarity