How to Manage the Fatigue from Taking a PARP Inhibitor

The American Society of Clinical Oncology (ASCO) guidelines recommend PARP inhibitors be offered to women, with or without genetic mutations, who are newly diagnosed with stage III or IV ovarian cancer and have improved with chemotherapy.

"Thankfully, with more experience using these drugs, we’ve gotten a lot better at management strategies," says Dr. Ramez Eskander, gynecologic oncologist at University of California, San Diego.

But most important in managing side effects is educating my patients, and being honest and open with them. "If I tell them, 'Take these pills, don’t worry, you’re going to feel great,' then I’m doing them a disservice. Why? Because when they feel fatigued and miserable, and they think something is wrong."

Instead, Dr. Eskander says it’s a better strategy to let patients know they may feel tired when they start this medication. "But the good news is, for the majority of patients, the fatigue will almost always stabilize about two months into treatment. Three months into treatment, it’s really not an issue."

Most of the oncologists SurvivorNet spoke with agree, saying that the first month on a PARP inhibitor can be tough, but that after that first month, for whatever reason, most patients adjust to the medication. The fatigue especially tends to pass, or else it's lessened to where it's no longer an issue.

So what can you do if you’re feeling fatigued that first month or two?

• Try some light exercise. Make sure you try to get a little bit of exercise each day because activity can help regulate our sleep, says Dr. Eskander. Light physical activity can actually help restore the body's energy reserves. Choose something you enjoy go for a walk, garden. And keep in mind that "during COVID-19 and the implications it’s had on many of our lives, it's impacted sleep for (a lot of people, including) many of our patients, and that can result in fatigue."
• Avoid long naps. Make sure you’re not taking naps in the middle of the day, which can disrupt your sleep in the evening, Dr. Eskander advises. Other oncologists suggest that if you do need a nap, make them shorter, more frequent power naps rather than long ones. Those break the cycle of fatigue.

Adjusting Your Medication Dose

Fatigue can be caused by low hemoglobin levels and your doctor will keep a careful eye on that. Most patients who are on PARP inhibitors will get regular testing to monitor their blood levels, and if doctors see counts start to drop, they may dose-reduce your medication to help alleviate the anemia and the fatigue. (In some cases, a blood transfusion may be necessary to continue treatment.)

In fact, it's not uncommon for women to need dose adjustments, either temporarily or long term. According to one oncologist, 30 to 50 percent of patients will require a dose reduction at some point.

"The other thing I educate my patients about is that not all fatigue is PARP-inhibitor related," Dr. Eskander says. “Many of my patients have come off chemotherapy, and they may be anemic from that. We check blood counts to make sure that that’s not the cause.”

Time Changes

One way to get around fatigue is to change the time a patient takes their pill. For instance,  Dr. Eskander has his patients take it in the evening so that the fatigue isn’t as disruptive.

According to another oncologist, if insomnia is an issue, patients who are on a one-pill-per-day dose may be able to take it in the morning rather than at night. Or they could take a break from their medication, maybe a week or two, and see how they feel.

Then after that time has passed they can be “re-challenged” with the same dose, or a reduced dose, to minimize the side effects. A lower dose doesn't necessarily make the treatment less effective; it's just a matter of finding the right dose for your body.

Many doctors say that overall, patients tend to tolerate PARP inhibitors well enough not to stop treatment, and they often encourage them to try to stick with it. That's because the drugs can have a positive effect on progression-free survival, which means the amount of time that a woman can live without their cancer getting worse.

Dr. Amanika Kumar of the Mayo Clinic who spoke to SurvivorNet, cautioned that women still need to speak with their doctor to evaluate the benefit of taking a PARP inhibitor to extend life, because there are very real side effects due to the toxicity of the drug.

"Patients with HRD (Homologous Recombination Deficiency) have a far better response than those without and those with BRCA mutations even more so. It is on us as clinicians to help patients understand the risks and benefits of treatment. Patients that have no mutation or HRD may choose not to go on maintenance (in fact I recommend they don't) because there is real toxicity to these meds."

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