Is HIPEC a viable treatment option for ovarian cancer?

HIPEC may be of benefit to some patients with ovarian cancer, but the studies conducted so far have been lacking in critical areas to support that conclusion.

Women diagnosed with ovarian cancer today have many more treatment options than just a few decades ago. For most patients, these therapies have changed an ovarian cancer diagnosis from a probable death sentence to something more akin to living with a chronic illness. Ovarian cancer is very serious, to be sure, but in the United States, it’s an illness that may be regularly managed with proper care and vigilance.

A greater understanding of the genetic make-up of ovarian tumors, the development of improved platinum-based chemotherapy drugs and the emergence of targeted therapy drugs, especially PARP inhibitors, have drastically improved outcomes for women diagnosed with the disease.

Another procedure gaining increasing attention today as a therapy for ovarian cancer is hyperthermic intraperitoneal chemotherapy (HIPEC).

While used for years to treat other abdominal cancers, such as colorectal and appendix cancers, HIPEC still has unproven efficacy when it comes to ovarian cancer. Does that mean HIPEC should not be used to treat some cases of ovarian cancer? No. The procedure may be of benefit, but the studies conducted so far have been lacking in critical areas to support that conclusion.

As a Medical Oncologist and President of Medicine & Science at Cancer Treatment Centers of America® (CTCA), I know how important it is to follow the science with new, emerging treatments, to make sure any supposed benefits have been vetted through appropriate clinical trials. Additional clinical research is needed to help us better determine which therapies are most appropriate in which situations, given each woman’s individual case history. Because ovarian cancer is likely to recur, possibly a number of times, how its treatment and management affects the patient has added significance. So, let’s take a look at ovarian cancer today, particularly the role HIPEC may play in the treatment of the disease. In this article, I will touch on:

If you’d like to learn more about how we treat ovarian cancer, or if you’ve been diagnosed with ovarian cancer and are interested in a second opinion on your diagnosis and treatment plan, call us or chat online with a member of our team.

Ovarian cancer’s improving statistics

Ovarian cancer, which develops in the egg-producing ovaries of the female reproductive system, is still the fifth leading cause of cancer-related deaths in U.S. women. However, because of strides made in the treatment of the disease, the American Cancer Society says the annual death rate from ovarian cancer has dropped 33 percent between 1976 and 2015.

The past five years has also seen a rapid and dramatic evolution in the treatment of ovarian cancer, in contrast to the previous 20 years.

For the 21,000-plus women expected to be diagnosed with the disease in 2021, a typical treatment may have included debulking surgery, which removes as much of the visible tumors and cancerous tissue as possible. Surgery may also be used to remove the ovaries and fallopian tube, or possibly, depending on the location and extent of the cancer, a hysterectomy to remove the uterus.

Chemotherapy treatment options

Chemotherapy drugs are a mainstay in the treatment of ovarian cancer.

Chemotherapy may be used prior to surgery, to shrink the tumors before their removal, and after surgery to kill remaining cancer cells. The standard chemotherapy used today is a combination dosage of carboplatin and paclitaxel.

Many therapies use these chemotherapeutic drugs intravenously, providing a systemic approach that delivers the chemotherapy throughout the bloodstream in order to attack the cancer cells in or near the ovaries. More recently, chemotherapy may also be given directly to the cancerous area. The procedure, called IP chemotherapy or intraperitoneal chemotherapy, allows the chemotherapy drugs to flow through a catheter directly inserted into the peritoneal cavity near where the ovaries are situated below the abdomen.

Delivering the chemotherapy drugs into the peritoneal cavity increases their concentration 10- to 20-fold and has been shown to improve overall survival. IP chemotherapy is usually given in six cycles.

The HIPEC approach

Hyperthermic intraperitoneal chemotherapy takes a different approach while also focused on the peritoneal cavity. The procedure is performed at the same time as aggressive surgical operation designed to remove all visible tumors. During this operation, once the tumor removal is completed, the cavity is bathed in a chemotherapeutic agent, often cisplatin and paclitaxel, to kill off remaining cancer cells. The chemotherapy drugs are heated under the assumption that cancers cells are less able to handle the heat than healthy cells, and that the heat makes it easier for the chemotherapy drugs to enter and destroy the cancer cells.

However, while randomized trials have demonstrated the effectiveness of the six-cycle IP chemotherapy treatments, research on HIPEC hasn’t delivered such conclusive results.

The question is, does HIPEC, which is basically a single treatment that involves surgery performed in tandem with a single chemotherapeutic bathing of the peritoneal cavity, improve overall survival? One trial suggests that may be the case, but it’s been harshly criticized because the control arm didn’t take into account the current availability of drugs like bevacizumab.

The HIPEC approach may make sense for an individual patient based on her discussions with her gynecological oncologist. But each patient needs to understand there’s limited trial data demonstrating the approach’s superiority over other options.

Questions over HIPEC’s efficacy doesn’t mean it shouldn’t be used as part of a patient’s therapy, and it certainly doesn’t mean it’s going to be excessively toxic. But the end result of the treatment may very well depend on the quality of the surgery, the quality of the surgeon and the expertise of the center where it is performed. The point is, there has to be an open and honest discussion about the evidence—or lack of evidence—concerning HIPEC as a clinically superior therapy to other options available today.

HIPEC requires a very aggressive surgical procedure. The idea that the patient will have no remaining disease after the procedure is usually a goal, not a requirement, of cancer surgery. With HIPEC, it becomes a requirement—the patient should have no physical evidence of disease after one heated chemotherapy treatment performed with the surgery.

Targeted therapy options

Other treatment options are having very positive results with ovarian cancer patients. Two of the most promising are targeted therapy treatments, sometimes in combination with chemotherapy. These treatments involve either bevacizumab or PARP inhibitors.

Targeted therapy works differently than chemotherapy, which targets fast-growing cells throughout the body. The drugs used in targeted therapy are directed to specific features on the cancer cells, preventing those cells from being able to perform critical tasks needed for their survival. By attacking genetic features that regulate cell growth and division, these targeted therapy treatments work to stop or slow tumor growth.

To determine whether a patient’s cancer cells have those specific features and may benefit from the therapy, the patient will need advanced genomic testing. This testing scans the genetic profile of a woman’s tumor cells, to determine whether the cells have a known mutation that an existing drug therapy is able to target.

One targeted therapy uses bevacizumab (Avastin®), an angiogenesis inhibitor that disrupts the cancer’s ability to make the new blood vessels required to feed itself. The drug basically starves the cancer by blocking the vascular endothelial growth factor (VEGF) protein needed to form those blood vessels.

PARP inhibitors, another targeted therapy, stop the cancer cells from being able to repair damage to their DNA, essentially killing them. Cancer cells are just as likely as healthy cells to sustain damage to their DNA. Both rely on the ADP-ribose polymerase (PARP) protein to send out a call for repair genes when needed. PARP inhibitors such as olaparib (Lynparza®), rucaparib (Rubraca®) and niraparib (Zejula®) attempt to interfere with the repair of cancer cells in ovarian cancer patients.

More HIPEC clinical trials needed

One essential ingredient missing from the discussion to date is a phase 3 randomized trial comparing HIPEC to a chemotherapy regimen of carboplatin and paclitaxel with bevacizumab, followed where appropriate by an anti-PARP maintenance therapy. The goal would be to determine whether HIPEC has any impact on progression-free survival for ovarian cancer patients. The trial would compare HIPEC to the therapy we use today in frontline settings.

Progression-free survival, which measures how long after treatment a patient goes without her cancer progressing, must be the primary endpoint on trials, not overall survival. Because once a patient’s disease progresses, doctors have many drug therapies they can use to increase overall survival—thus having no bearing on the effectiveness of the original therapy. When used as a primary endpoint, progression-free survival has demonstrated to be very relevant in bevacizumab trials, showing improvement in primary therapy, recurrent disease and resistant disease.

The CTCA approach

Our patient-centered approach includes a willingness to incorporate a patient’s viewpoints. At CTCA, we are very much focused on system management during the illness, so we’re treating the whole patient, not just the cancer. Besides cancer doctors, our multidisciplinary teams include dietitians, naturopathic providers, pain management physicians, behavioral health professionals and spiritual support providers. We also take into consideration fertility-preserving options for younger women who may want to have children in the future.

The bottom line, managing ovarian cancer requires time and effort, even after treatments are completed. But there are lots of reasons to be encouraged, because we have therapies that have been shown to control the disease for years after a recurrence.

If you’d like to learn more about how we treat ovarian cancer, or if you’ve been diagnosed with ovarian cancer and are interested in a second opinion on your diagnosis and treatment plan, call us or chat online with a member of our team.