Choosing Sides: Treatment Decisions for Recurrent Ovarian Cancer Must Consider Side Effects

Patients with ovarian cancer who experience disease recurrences can have potentially helpful options from a large array of drugs, each of which can bring on side effects.

Luckily, doctors have a variety of ways to relieve or prevent these discomforts. At the same time, scientists are working to develop new treatments that may be both efficacious and easier for patients to tolerate.

When making treatment decisions, it’s important to avoid compounding any lingering side effects — especially if they could become permanent, said Kathleen Moore, M.D., an associate professor of gynecologic oncology and director of the Oklahoma TSET Phase I Clinical Trials Program at Stephenson Cancer Center at the University of Oklahoma Health Sciences Center.

Moore’s No. 1 consideration is neuropathy, a numbness and/or tingling in the hands and feet: “We don’t want to make neuropathy worse so patients need an assistive device to walk or can’t feel their feet so they’re at risk for infections or hurting themselves.” This can be a side effect of taxane chemotherapies (paclitaxel or docetaxel), one of which is typically given with the chemo­therapy carboplatin as part of initial treatment, in addition to surgery. Firstline therapy may also include the targeted drugs Avastin (beva­cizumab) or Lynparza (olaparib). When disease recurs, some of these drugs may be used again.

Other side effects include fatigue, which may improve with physical activity, and blood count problems, which can be helped with dose adjustments.

“Some people can’t tolerate oral therapies, whose side effects remain steady, rather than peaking and ebbing, as the side effects from infused chemotherapies do. Others have a very low threshold for nausea and vomiting, and those factors will inform our decisions,” Moore said — although she noted that nausea is treatable with medications.

Women who’ve been treated for ovarian cancer in the past know that taxanes “cause 100 percent hair loss,” Moore added. Although they’re not often covered by insurance, cold caps are an option that can help women keep their hair.

If more medications are given due to disease recurrence, patients might also experience new side effects. Hand-foot syndrome and mouth sores (treatable with special mouth­wash) can develop while taking Doxil (pegylated liposomal doxorubicin). PARP inhibitors can cause shortness of breath, acid stomach (treatable with over-the-counter medication) and insomnia. Joint pain (potentially treatable with anti-inflammatories) and high blood pressure (treatable with antihypertensive therapy) can arise while taking Avastin or the PARP inhibitor Zejula (niraparib). Also with Zejula, patients can experience heart palpitations (treatable by delaying a dose of the medication), as well as anemia and nausea.

“Most of these are (of) very low severity and manageable with behavior modifications or medications, and with PARPs, they all get better with time,” Moore said.

Alicia Dellario, 55, of West Chester, Pennsylvania, received a diagnosis of stage 3c ovarian cancer in 2014 and is being treated for a third recurrence. She has had many side effects: high blood pressure, mouth sores, diarrhea, dehydration, constipation, nausea and fatigue. Now in a clinical trial testing Lynparza in BRCA gene mutation-negative, homologous recombination-deficient ovarian cancer, she’s added another one: depression.

“I don’t like the pill form at all. You never get out from under the side effects,” said Dellario, who will remain on Lynparza as long as it works for her. “With infusion, you have a really bad couple of days and then come out of it and can have some decent days. With the pill for Lynparza, the nausea for the first four months was so brutal, and the extreme fatigue never subsides. My tumor is shrinking, but I’m in a really bad depression because I just don’t see the end of the tunnel.”

Scientists are working on new treatments that might cause fewer side effects. Antibody-drug conjugates combine a chemotherapy and a targeted drug that directs it toward cancer cells. “I could easily see these replacing paclitaxel with an equivalent but better drug that doesn’t cause hair loss and causes far less neuropathy. Some cause nausea, but not a lot,” Moore said.

Furthest along in development is mirvetuximab soravtansine, recently studied in a phase 3 clinical trial in previously treated folate receptor alpha-positive, platinum-resistant ovarian cancer, and also being tested in additional situations and tumor types, Moore said. Its side effects include manageable diarrhea, fatigue and blurred vision.

The doctor noted that many trials of drugs for ovarian cancer include methods of capturing patient reports about side effects. “We want to make sure our patients’ voices are heard,” she said.

That makes sense to Dellario, who has a lot of knowledge to pass along. For example: “Many antiemetic (antinausea) drugs cause constipation, which can be a real problem. I don’t feel like that’s communicated as well as it could be.”