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SRI Magazine 2016

SRI Magazine 2016

Delivering carboplatin into the abdominal cavity for ovarian cancer is well tolerated by patients: study

Research into the “best” regimen accounts for toxicities as well as survival

Epithelial ovarian cancer (EOC) is the most common type of ovarian cancer. About 80% of cases originate from cancerous cells that form in the epithelium, the thin tissue covering the outer layer of the ovary. The risk of developing ovarian cancer increases with age and with a family history of the disease. Most women who are diagnosed with it are aged over 50 years.

Dr. Danielle Vicus, a gynecologic oncologist-surgeon and researcher at Sunnybrook Research Institute, treats women with advanced-stage EOC at Sunnybrook’s Odette Cancer Centre. “At that point, the disease is not only confined to the ovary, but also in other areas in the abdominal cavity,” Vicus says. “It spreads like you had a handful of rice, and you release that rice into the abdominal cavity and those little grains stick to different areas within the peritoneal cavity, such as the bowel and uterus.”

The five-year survival rate for these patients ranges from 30% to 40%. Surgery is the main treatment and allows surgeons to determine how far the cancer has spread from the ovary. Patients undergo a complete hysterectomy to remove the uterus, ovaries and fallopian tubes, along with the omentum, a layer of fatty tissue that covers the abdominal area like an apron. The aim of the surgery is to remove as much cancerous tissue as possible and leave no lesions larger than one centimetre, says Vicus. Following surgery, patients are treated with chemotherapy once every three weeks for six cycles.

“We can’t cure patients without a multimodality approach, in other words, surgery together with chemotherapy. Neither of those alone can effectively treat ovarian cancer,” she says.

To date, there are limited data on the efficacy of carboplatin and cisplatin, which are platinum-based chemotherapy drugs to treat cancer. The optimal means of administering these agents also remains controversial. Research has shown patients have better survival with the use of intraperitoneal (IP) cisplatin. This method involves placing an injection port directly into the abdominal cavity during surgery so that the cancerous cells remain exposed to the drug at a high concentration for a longer period. The other option uses the traditional intravenous (IV) method to deliver chemotherapy.

When IP cisplatin is infused regionally, however, it is associated with greater toxicities that prevent patients from completing the treatment, says Vicus. These include nausea, vomiting, abdominal pain and neuropathy, which causes numbness or weakness from damage to sensory nerves.

Equally effective is IV carboplatin, which studies have shown has less toxicity than IV cisplatin. The combination of IV carboplatin and paclitaxel, a drug used to treat ovarian cancer, has become the first-line regimen in treating advance-stage EOC. It was unclear whether carboplatin would work if it were infused intra-abdominally, although preliminary studies suggested it was effective, notes Vicus, which helped inform her practice. “We were one of the first centres to actually start using IP carboplatin versus cisplatin,” she says.

To understand better the efficacy of carboplatin compared to cisplatin, Vicus co-authored a retrospective study to compare the toxicity and tolerability of the two IP regimens for women with advanced-stage EOC following surgery. The researchers looked at patients who received IP chemotherapy at Sunnybrook and the Princess Margaret Cancer Centre between 2005 and 2014. Of the 141 patients, 77 received the IP cisplatin and 64 received the IP carboplatin.

The researchers found a high completion rate in both groups. Those in the IP carboplatin group, however, experienced significantly fewer gastrointestinal, neurological and blood-related side effects. “We don’t think one is better than the other from a survival perspective, but IP carboplatin is much more tolerable. It doesn’t cause patients to feel exhausted,” says Vicus. “We could possibly offer it to a more diverse population, and it wouldn’t have so many side effects.”

The study also looked at rates of overall survival and progression-free survival (the time from the first day of treatment to the date on which disease progresses or causes death) as secondary outcomes. There was no difference between the two regimens, Vicus notes. “We weren’t surprised, but it reinforced what we thought—that the [IP carboplatin] regimen we are using here at Sunnybrook could be a regimen that should be used at other centres and offered to more patients,” she says. “Patients tolerate the IP chemotherapy well because there’s less toxicity and it looks like it improves quality of life.”

The results from clinical trials underway at the Odette Cancer Centre will further inform practice, says Vicus, and help to determine whether IP carboplatin can become the first-line agent to treat patients with ovarian cancer. “What we’re trying to do is cure as many patients [as possible], improve their quality of life and give them the longest progression-free survival that we can,” she says. “So any treatments like IP chemotherapy that can give women more time to live and also give them a better quality of life, that of course is what we’re advocating for.”