Pittsburgh Post-Gazette (PA)

08-26-13

Aug. 26--Despite the many chemotherapy drugs for ovarian cancer, none is fully effective, which means the cancer commonly recurs. That poses challenges for physicians, who must use knowledgeable guesswork to figure out a drug strategy for each patient.

"With ovarian cancer, when it recurs, the best way to use the drugs is not well defined," said Thomas C. Krivak, director of gynecologic oncology research at Allegheny Health Network. "Some will use different combinations. If you have three doctors, you will get three different combinations."

But in a step toward personalized medicine, a South Side company's test known as ChemoFx analyzes chemotherapy-drug effectiveness on a patient's live cancer cells to help identify the drug regimen with the best potential to fight the recurrent cancer.

Patients generally survive longer when the cancer is sensitive rather than resistant to chemotherapeutic drugs. Unfortunately, in many types of cancer the response rate is often about 25 percent. The challenge is determining cancer sensitivity prior to treatment. While the test, developed by Precision Therapeutics Inc., has been available for years, it's been unclear whether it improved outcomes.

That is, until now.

A study published online in the journal Gynecologic Oncology shows that ChemoFx -- approved for laboratory prognostic use and covered by Medicare -- is effective in extending the lives of patients with ovarian cancer by 14 months. That represents a 65 percent improvement in overall survival. Essentially, the test was able to predict whether ovarian-cancer patients would live longer if they took a particular chemotherapy.

The study, which involved Dr. Krivak, concludes that ChemoFx may be used as "a very useful tool for optimizing treatment selection when there are multiple clinically acceptable and equivalent treatments available."

If doctors can determine what chemotherapy drugs the patient's cancer cells respond to, once the cancer returns, they can narrow treatment options and spare the patient ineffective, toxic treatments that bring unwanted side effects, the study indicates. It also would provide new treatment options for many more patients. As the study says, the test can "assist clinicians in the optimal prioritization of therapy."

The gist of the study, Dr. Krivak said, is that ChemoFx can be used to provide better treatments for patients with ovarian cancer and extend their lives.

Live-cell samples from a biopsy, once sent to Precision's laboratory, undergo a five-step process involving robotic automation. Cells are grown, then treated with commonly used chemotherapies to determine sensitivity or resistance. A report sent to the physician details which drugs or drug combinations were effective.

The study involved 262 patients from 2004 to 2011 whose ovarian cancer had recurred, with 55 percent whose cancers were sensitive and 45 percent whose cancers were resistant to platinum-based chemotherapy drugs during the initial round of treatment. Resistance and sensitivity are based on whether the cancer returned earlier or later than six months.

Use of ChemoFx demonstrated improved progression-free survival and overall survival for patients, regardless of whether they were judged to be sensitive or resistant to platinum-based therapies, the study concludes.

"These are definitive results in a clinical study over an eight-year period and involving more than 30 institutions nationally," said Sean McDonald, Precision president and CEO. "Basically it showed that through the use of this test, physicians can find the best therapy, and women lived 65 percent longer."

Robert W. Holloway, director of gynecologic oncology at Florida Hospital Cancer Institute in Orlando, said the study doesn't mean outcomes for each future patient automatically will improve, but it strongly suggests that choosing sensitive drug therapy for the first treatment following cancer recurrence "significantly improves survival, rather than selecting drugs purely based on other considerations."

"When a less effective regimen is chosen first, the patient may progress with symptomatic recurrences more quickly, decline in overall health faster and be unable to try other therapies that could achieve short-term responses or disease stabilization," he said.

The recurrence of ovarian cancer usually results in reduced quality of life through bowel dysfunction, pain and an inability to maintain proper nutrition, leading to generalized weakness and death.

"Getting a quick response [after the cancer recurs] means the patient might live to fight another battle another day, hopefully in another year," said Dr. Holloway, who did not participate in the study. "Losing the first battle of recurrence often means cutting the war short."

With the test long approved for use, Mr. McDonald said the company has tested more than 24,000 gynecological specimens sent to the lab by 1,500 doctors in the past 2 1/2 years. "On average, when we receive a biopsy, the doc sends a list of drugs he or she is considering, often nine or 10 chemotherapies."

For ovarian cancer, there are more than 20 approved chemotherapy drugs, "none of which works particularly well, which clearly makes therapy decisions even more complex for the physician and the patient," he said, noting the test's ability to personalize the treatment for the patient's unique cancer.

The company is developing similar tests for lung and colon cancer with confidence that "this technology will work across a wide range of cancers," Mr. McDonald said.

Fredric Price, West Penn Allegheny Health System director of gynecologic oncology, said he's been using the test for several years to reduce patient exposure to toxic drugs that aren't effective.

"I've been using it for decision-making but without much long-term data" on whether the test was bringing improved outcomes, he said. "Now that we are seeing the results ... we can see that it might make a difference."

Information obtained from tumor cells allows the physician to "tailor the treatment to the patient's own biology."

"I've been waiting for this data to come out before using the test on a regular basis," Dr. Price said. "I've been hoping that this information would come out. There is value to it."

The holy grail in gynecological cancers remains early detection, which would improve outcomes. That's yet to happen. But the test does mark an improvement in cancer care, Dr. Price said.

"I would say these are cancers with a high likelihood of recurrence, but there are more longtime survivors," he said.

Dr. Krivak said the hope is to turn ovarian cancer into a chronic rather than fatal disease.

"It's baby steps in cancer or a series of baby steps in finding the best targeted chemotherapy," he said. "But this is one of the first steps in customized patient care."

David Templeton: dtempleton@post-gazette.com or 412-263-1578.

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