Managing Side Effects During PARP Inhibitor Treatment

One of the most promising new treatments providing hope for women with ovarian cancer is a class of drugs called PARP inhibitors, which work by preventing cancer cells from repairing their genetic material, resulting in their inability to replicate. The American Society of Clinical Oncology (ASCO) has 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.

Unfortunately, like most effective cancer treatments, these powerful drugs have high toxicities that can cause some uncomfortable side effects, including gastrointestinal problems like nausea and diarrhea.

The three PARP inhibitors that are FDA-approved to treat ovarian cancer are:

• Olaparib (Lynparza)
• Rucaparib (Rubraca)
• Niraparib (Zejula)

PARP inhibitors are given in pill form, and kill cancer cells in a different way than chemotherapy. But some of the side effects that patients experience are the same. “I basically tell my patients that these oral therapies are just like intravenous chemotherapy, except I’m putting it down your stomach,” explains Dr. John Chan, gynecologic oncologist at Sutter Health in the Bay Area in California. “So these patients will get some gastrointestinal side effects.”

Common Side Effects from PARP Inhibitors

All three of the approved PARP inhibitors cause similar side effects. Which ones you experience can vary, depending on whether you take PARP inhibitors alone or in combination with other chemotherapy drugs or treatments.

In general, PARP inhibitors side effects can include:

• Fatigue
• Nausea
• Diarrhea
• Appetite loss
• Pain in abdomen
• Changes in taste

Another type of side effect is related to the effect of PARP inhibitors on your bone marrow, where healthy new blood cells are made. As these drugs disrupt DNA repair in cancer cells, they can also disrupt healthy blood cells, leading to low red blood cell (anemia) and white blood cell counts. Your blood counts will be monitored during treatment, and if counts drop too low the dose may be lowered or the treatment paused or altered.

Managing Gastrointestinal Side Effects

The first month on a PARP inhibitor, in particular, can be hard to handle. Nausea can be a big problem. If you’re very nauseated, your doctor may prescribe an anti-nausea drug like metoclopramide (Reglan) or ondansetron (Zofran). Taking an anti-nausea medication 30 minutes before your PARP inhibitor may help prevent this symptom. For diarrhea, diphenoxylate and atropine (Lomotil) or over-the-counter Imodium may help.

Fatigue can be another common complaint with PARP inhibitors. The tiredness is often due to low hemoglobin – a protein that normally transports oxygen throughout your body. Your doctor can do regular blood tests to check your hemoglobin levels while you take PARP inhibitors, and give you a blood transfusion if it drops too low.

Adjusting Treatment

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. Your doctor may decide to adjust your dose, or even to put you on a temporary break from treatment.

Taking a lower dose of medication shouldn’t compromise the ability of the treatment to control your cancer. “Even with some dose reduction, these drugs, particularly niraparib, have been shown to have efficacy,” Dr. Chan says.

Going off the medication entirely for a few weeks can give you a reprieve from side effects without undermining your treatment’s effectiveness. “In these clinical trials, they actually gave the patients up to four weeks of break before restarting the medications again,” says Dr. Chan, adding, “When you restart these medications, sometimes it’s prudent to slowly ramp them up instead of restarting them on the full dose.”

Most side effects from PARP inhibitor treatment are temporary. The longer you take these medications, the better you should start to feel. “Within three months of treatment, most patients are able to tolerate the use of these drugs as a maintenance strategy,” Dr. Chan says. While PARP inhibitor side effects may be hard to tolerate at first, they shouldn’t stop you from staying on your cancer treatment. Talk to your doctor about what you’re experiencing, and about ways to manage the unwanted effects.

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