Targeted treatment for ovarian cancer to be studied at University Hospitals
Tuesday, February 28, 2012
CLEVELAND, Ohio — Physicians at University Hospitals Case Medical Center are developing four clinical trials to test a therapy that has been around for several decades, but which only recently has been used to treat ovarian, endometrial (uterine) and select other gynecologic cancers.
The studies, which physicians hope to begin this spring, have been designed for a very specific patient population — no more than a couple dozen women with ovarian or endometrial cancer will be enrolled in each one. The trials will help researchers compare and learn relatively quickly how to use heated intraperitoneal chemotherapy, or HIPEC, as effectively as possible, said Dr. Robert DeBernardo, a gynecologic oncologist at UH and assistant professor at Case Western Reserve University School of Medicine.
The procedure, administered in the operating room right after surgery to remove malignant tumors or tissue, flows a hyperthermic — or heated — sterilized chemotherapy solution through catheters directly into a patient’s abdominal cavity. The heat makes cancer cells “leak” so chemotherapy can enter the cells more effectively.
The effect of chemotherapy delivered directly to the abdomen is more potent than intravenous delivery, which takes longer to reach the intended area. And because the targeted delivery of HIPEC minimizes the rest of the body’s exposure to the treatment, it helps reduce some side effects, such as hair loss.
“Giving chemotherapy in the [operating room] is complicated, but it’s not something that can’t be done,” DeBernardo said. “We need to really show: Is this a beneficial therapy?”
Not only will the studies shed light on how well HIPEC controls when and where the cancer recurs, but they will also focus closely on side effects, costs and the length of hospital stays.
Here are the Phase 1 trials:
• A study involving the use of heated chemotherapy for ovarian cancer that has spread to the chest. What the surgical team has dubbed HITEC (the “T” coming from the word intrathoracic) is performed after minimally invasive lung surgery. “To my knowledge, no one has treated ovarian cancer [that has spread to] the chest like this,” DeBernardo said.
• A study for advanced ovarian-cancer patients whose cancer is in remission following surgery and chemotherapy. The patients will undergo HIPEC to prevent recurrence.
• A study for patients whose cancer recurs; HIPEC will be performed following surgery.
• A study for patients who undergo chemotherapy prior to surgery and HIPEC during the surgery.
Ovarian cancer is especially challenging to treat, as it is often not detected until it has spread. The cancer antigen 125 blood test, which can detect elevated levels of CA-125 — a trait often found in women with ovarian cancer — is not recommended as a screening test in women with an average risk of the disease because elevated levels can signal many other conditions.
Over the past two decades, treatments have evolved and improved, says DeBernardo.
Not only has it become easier to perform aggressive tissue-removing surgery (the primary way to diagnose ovarian cancer), but surgeons have become more specialized in cancer-tissue removal. Women also are able to better tolerate treatment.
“The thing about women with ovarian cancer [is,] we don’t cure very many people with ovarian cancer,” DeBernardo said. “We can control it, we can keep it at bay. But it almost always comes back. That’s where HIPEC comes in. It may improve things.”
The Cleveland Clinic began treating abdominal cancers — appendix, colorectal, gastric, ovarian and peritoneal mesolthelioma (a cancer of the lining of the abdominal cavity) with HIPEC in 2010. UH followed suit last summer, with DeBernardo working with other surgical oncologists and general surgeons to launch the program at UH Seidman Cancer Center.
Buoyed by the results of a national study that appeared in 2006 in the New England Journal of Medicine that showed a higher rate of survival for women with ovarian cancer who were treated with HIPEC versus intravenous chemotherapy, hospitals began to explore the HIPEC option.
“The unfortunate fact is, even though it’s good science, there is still only a minority of women getting offered that treatment,” DeBernardo said. The reasons are varied, and include that not all women have ready access to a hospital with a gynecologic on-
cologist or other skilled staff who are able to integrate HIPEC as part of treatment.
Last August, led by DeBernardo, UH launched a dedicated HIPEC program for gynecological cancers. The surgical team performed its first HIPEC treatment in August 2011. Since then, there have been more than two dozen cases.
Jan Belleville of Hubbard was DeBernardo’s first HIPEC patient.
Other than feeling something — not pain, but something — in her lower abdomen in the summer of 2006, Belleville had no reason to think it was ovarian cancer.
“I had had fibroids and thought that was all it was,” said Belleville, 68. But it wasn’t.
Belleville was diagnosed with Stage 4 ovarian cancer, which by then had spread through her abdominal cavity to her liver. Her first surgery included radiation therapy. Chemotherapy followed.
After being in remission for a year, Belleville’s cancer returned to her liver. She had another operation, followed by more chemotherapy and radiation. The cancer went into remission for six months, then came back. After more chemotherapy, remission again for three months. But the cancer came back again. This time it had spread to her lungs.
After treating Belleville with different types of chemotherapy that proved ineffective, DeBernardo and his colleague, Dr. Jason Robke, decided to do something else.
Last summer, they approached her about having HIPEC/HITEC surgery. She would be their first case.
“I never have doubted that I was being guided in the right direction,” Belleville said.
In late July, she had the first of two HIPEC/HITEC operations, on the left side of her chest. Four weeks later, surgeons operated on the right side. Those surgeries — which were each roughly three hours long, including about 90 minutes for administering the chemotherapy — were the seventh and eighth since she was first diagnosed.
The surgeries stabilized Belleville’s levels of CA-125, the protein in the blood that is found in ovarian cancer cells at a much higher level than in normal cells.
Shortness of breath and lack of energy earlier this month prompted more tests; X-rays detected spots on her lungs, evidence that the cancer had returned there.
Despite the news, Belleville and her husband went ahead with a planned vacation to Florida. Last week, she started intravenous chemotherapy.
“I think it bought me a really nice Thanksgiving, a beautiful holiday over Christmas,” an upbeat Belleville said about the six-month remission that followed her HIPEC/HITEC procedure. “I don’t consider this [recurrence] a setback.”