PARP Inhibitors Explained
- PARP inhibitors are a targeted therapy that fight ovarian cancer at a genetic level by hampering cancer cells’ ability to grow and divide.
- PARP inhibitors provide the most benefit to women with BRCA mutations however now almost all women who’s cancer has shown a response to platinum chemotherapy may benefit regardless of genetic make-up.
- PARP inhibitors are most effective for cancers that have a germline or tumor mutation.
- PARP inhibitors can have significant side effects so it is important for doctors to weigh the potential benefits versus the risks.
“PARP inhibitors originated from the work of three Nobel laureates in 2014 who focused on cancer cells’ DNA repair mechanism,” explains Dr. John Chan, gynecologic oncologist at Sutter Bay Medical Foundation in the San Francisco Bay Area.
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PARPs (or Poly (ADP-ribose) polymerases) are proteins that play an important role in the life cycle of all cells, cancerous or not. When a double strand of DNA is broken into a single strand, or damaged, PARP enzymes rush in to repair the damage so the cell can continue to grow and thrive.
“PARPs are almost like repair trucks that essentially go over the railroad of the DNA and repair the broken or damaged strand,” Dr. Chan says. PARP inhibitors interrupt that process so repairs cannot be completed and cancer cells die off.
In patients with advanced cancer, who have a 50 to 60 percent chance of their cancer returning, PARP inhibitors may reduce the risk of recurrence. They seem to be most effective for patients who have a BRCA-1 or -2 mutation, and for those who have fast-growing, high-grade disease. But recent studies suggest there may be benefits for women who do not have the BRCA mutations as well.
The Role of PARP Inhibitors in Ovarian Cancer
After initial chemotherapy, studies suggest PARP inhibitors may help reduce the odds that a cancer will recur. In fact, studies suggest that using PARP inhibitors either to help fight cancer initially during a combination of chemotherapy and surgery, or as maintenance, to help keep the cancer from recurring after chemotherapy and surgery, or even both can significantly extend the length of time patients are cancer-free or keep their cancer from worsening.
PARP inhibitors for ovarian cancer include:
Common Side Effects of PARP Inhibitors
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, while each PARP inhibitor has its own side effect profile, some do overlap and can include:
- Nausea
- Vomiting
- Stomach upset
- Fatigue
These side effects can be intolerable for some patients, but in many cases, doctors can offer options to alleviate or even eliminate them. Plus, when it comes to gastrointestinal upset, doctors have multiple tools at their disposal. Common anti-nausea medications include:
- Prochlorperazine (Compazine)
- Promethazine (Phenergan)
- Ondansetron (Zofran)
- Granisetron (Kytril)
- Olanzapine
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.
Rare Side Effects of PARP Inhibitors
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. As a result, a subset of patients encounter side effects of PARP inhibitor treatment related to bone marrow suppression. Two of the most common:
- Reduced blood cells counts: Since bone marrow makes both red and white blood cells, PARP inhibitor treatment may cause a drop in these cell counts. Patients may notice fatigue, reduced immunity, and light-headedness.
- Reduced platelet counts: Platelets play a role in blood clotting, so low platelet counts can cause excessive bleeding, easy bruising, and blood in the urine or stool.
Toward Reduced Toxicities
No matter which PARP inhibitor protocol you’ve embarked on, doctors can modify your treatment schedule to reduce side effects. A few possibilities:
- Discontinue treatment for a brief time period
- Reduce the dose
- Transition to another PARP inhibitor to see if there’s any improvement
In fact, navigating treatment with a PARP inhibitor is really no different from any other form of therapy. In every case, it’s about getting the maximum benefit from treatment while weathering the fewest side effects.
Dr. Amanika Kumar of the Mayo Clinic who spoke to SurvivorNet separately, 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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