PARP Inhibitor Side Effects

Recent studies suggest that using PARP inhibitors either as an initial therapy, maintenance therapy, or both, significantly extends the length of time patients are cancer-free or their cancer worsens. There are three PARP inhibitors currently approved by the FDA: Lynparza (olaparib), Rubraca (rucaparib) and Zejula (niraparib).

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.

Side Effects of PARP Inhibitors

Like chemotherapy, PARP inhibitors come with a host of side effects. Often it can be difficult to determine what is causing a specific side effect: the disease itself, a recently finished cycle of chemotherapy, or new treatment with a PARP inhibitor.

“Fatigue is one of the side effects that gets worse during the first few months after patients complete standard chemotherapy. So if you’re finishing chemotherapy and starting on a PARP inhibitor, it can be difficult to determine which of the two therapies is contributing most to the fatigue,” Dr. Parker says.

Whether or not you’ll experience significant side effects from PARP inhibitors depends on a number of factors, including which PARP inhibitor you’re taking, what dose you’re ingesting, and whether you’re using it alone or in combination with other therapies.

Still, the side effects of most PARP inhibitor protocols are largely the same and include:

• Nausea
• Vomiting
• Stomach upset
• Fatigue

These side effects can be intolerable for some patients, but when they’re not doctors can offer options to alleviate or even eliminate them. “The anti-nausea medications we use for chemotherapy also can benefit patients taking PARP inhibitors,” Dr. Parker says. They include:

• Odanesetron (Zofran)
• Granisetron (Kytril)
• Olanzapine

“Olanzapine is one that we typically don’t use as often in chemotherapy but it can help in PARP inhibitor-induced nausea,” Dr. Parker says.

Mitigating Side Effects

PARP inhibitors disrupt how cells repair damaged DNA; they kill off tumor cells and healthy cells simultaneously and as a result are quite toxic, which is why patients may feel fatigued and nauseous. Fortunately, there are a number of things doctors and patients can do to help minimize the side effects of PARP inhibitor treatment.

On the physician side:

• Discontinue treatment for a brief time period
• Reduce the dose
• Transition the patient to another PARP inhibitor to see if there’s any improvement

“I’ve found that having the patient adjust when they take the medication can have an impact as well, especially for the PARPs with once-a-day dosing,” Dr. Parker says.

On the patient side:

• Exercise: While it may be counterintuitive, exercise can help alleviate side effects, especially fatigue. In fact, performing specific exercises and moving your body can help alleviate chemotherapy side effects like neuropathy and enhance recovery. “Some of the physical therapy providers here in our region provide cancer renewal types of physical therapy that really work at building strength and mobility,” Dr Parker says.
• Eat well: Even though nausea may make it more difficult to eat a nutritious diet, it’s important to make sure that you’re eating appropriately, getting enough protein, and not losing weight.
• Breathe: Women undergoing cancer treatment should take time out for self-care. Meditation and deep breathing exercises, for example, can help lift your spirits and provide you with the emotional and physical strength you need in the days following surgery.

As a result of the side effects, 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."

If you’re able to nurture your body and build up your endurance before and during treatment, you’ll be able to start PARP inhibitor treatment on healthier footing  and recover from treatment more quickly.

 

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