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Coping With PARP Inhibitor Side Effects

Dr. John Chan Sutter Bay Medical Foundation

PARP Inhibitor Side Effects

  • PARP inhibitors each have their own toxicities which produce side effects
  • PARP inhibitors may produce more side effects than intravenous chemotherapy
  • There are a few danger side effects however they are exceedingly rare

Ovarian cancer treatment is complex and includes a variety of therapeutic options. A relatively new class of drugs, PARP inhibitors, are increasingly showing promise in the fight against ovarian cancer. Most recently, the American Society of Clinical Oncology (ASCO) released new guidelines recommending 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. But they also comes with some unfortunate side effects.

“When we first tested some of these PARP inhibitors in the recurrent patients, we thought they would be well tolerated, not just from a convenience profile, but also from a toxicity profile,” says Dr. John Chan, gynecologic oncologist at Sutter Bay Medical Foundation in the Bay Area. “We were surprised that these oral therapies, even though they are just pills, can give patients more side effects, even compared to intravenous chemotherapy.” But PARP inhibitors are still an invaluable tool in ovarian cancer treatment.

Common Side Effects of PARP Inhibitors

Recent studies suggest that using PARP inhibitors — either as first-line therapy, maintenance therapy, or both, significantly extends the length of time patients are cancer-free or before their cancer worsens.

These studies tested the following therapies among women with high-grade epithelial cancers:

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 some PARP inhibitor protocols do overlap and include:

  • Fatigue: Over 50 percent of patients suffer from severe fatigue while on PARP inhibitor treatment. “Often the fatigue that patients experience on a PARP inhibitor supersedes what they might face while on intravenous chemotherapy,” Dr. Chan says.
  • Bone marrow suppression: Since PARP inhibitors disrupt how cells repair damaged DNA, killing off tumor cells and healthy cells simultaneously, the bone marrow and blood cells may take a hit. “Patients get anemic because their red blood cells are low. They get neutropenic, meaning their white blood cells are low. And patients also get thrombocytopenia, which means their platelets, which are cell products that help them clot their blood, also gets severely compromised,” Dr. Chan says.
  • Nausea: Like chemotherapy, PARP inhibitors may cause gastrointestinal upset, including nausea and vomiting. Fortunately, doctors can prescribe the same anti-nausea medications they use for patients undergoing chemotherapy. Most of these anti-nausea medications last for more than eight hours. So if you have a single day dosing with a PARP inhibitor, taking anti-nausea medication the evening before treatment can help reduce or even eliminate nausea. These medications include:
  • Odanesetron (Zofran)
  • Granisetron (Kytril)
  • Olanzapine

Toward Reduced Toxicities

Since PARP inhibitors disrupt how cells repair damaged DNA, killing off tumor cells and healthy cells simultaneously, fatigue, bone marrow suppression and nausea make sense. But doctors can take steps up front to help patients better navigate treatment.

“Before patients start on PARP inhibitors, it’s important to make sure that they’ve recovered from suppressive drugs that they received intravenously,” Dr. Chan says. “Once they start, it’s important to continue monitoring them to make sure that their bone marrow is not compromised.”

If side effects are interfering with the patient’s health or quality of life, there are a number of things doctors and patients can do to minimize the side effects of PARP inhibitor treatment.

On the physician side:

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

On the patient side:

  • Exercise: While it may be counterintuitive, exercise can also help alleviate side effects, especially fatigue.
  • Eat well: Even though nausea may interfere with your ability to eat a healthful diet, it’s important to make sure that you’re eating appropriately, getting enough protein, and not losing weight.
  • Self-care: It’s important to take time out for self-care during treatment. 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.

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 treatment with PARP inhibitors doesn’t feel right to you, to talk to your doctor about alternatives. Ovarian cancer treatment is complex, but doctors have more tools at their disposal than ever before.

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John Chan is a gynecologic oncologist with Sutter Bay Medical Foundation. Read More