Factors Associated with Non-Completion of IP/IV Chemotherapy in Women with Epithelial Ovarian Cancer

A recent study conducted in women with epithelial ovarian cancer (EOC) found that non-home discharge and higher Eastern Cooperative Oncology Group (ECOG) status following cytoreductive surgery (CRS) were associated with non-completion of intraperitoneal with intravenous (IP/IV) chemotherapy. This is one of the first studies that closely examined the reasons behind non-completion of IP/IV chemotherapy in women with EOC.

“We had a very high-rate (71.9%) of IP/IV chemotherapy completion in our study,” says gynecologic oncologist Robert DeBernardo, MD, study supervisor. “Two factors correlated highly with women not being able to complete all six treatments — one was having to go to rehabilitation after hospital discharge following CRS and the other was performance status, or the patient’s level of fitness at the time of surgery.”

Dr. DeBernardo further notes that the extent of abdominal surgery did not correlate with IP/IV chemotherapy completion and that even those patients who had more radical surgery completed the treatment at similar rates.

Late diagnosis reduces the odds of a positive outcome

The 5-year overall survival (OS) for patients with EOC ranges between 30% and 40% and the current standard-of-care is a combination of CRS and adjuvant chemotherapy with platinum and taxane. Dr. DeBernardo says the overall prognosis for women with EOC is very good if the diagnosis is established early in the course of the disease.

“When the cancer is caught early and if it is confined to the ovary, or even the pelvis, outcomes are excellent,” he says. “We cure almost every patient with ovarian cancer confined to the ovary and probably 70% of patients with cancer confined to the pelvis.”

However, he explains that most women with EOC are diagnosed at an advanced stage when the cancer has already spread out of the pelvis and into the abdomen or the chest. The decision on whether to do surgery or chemotherapy first in these women largely depends on the treating physicians and patient characteristics.

“Many of us believe that upfront surgery is probably better especially when followed by the administration of IP chemotherapy, but a number of trials have shown that giving chemotherapy a chance to shrink the cancer can make the surgery less morbid or simpler,” he says. “Of all the studies that have been done in women with ovarian cancer to date, the best outcomes were seen in those who had surgery upfront followed by chemotherapy given directly into the abdomen.”

Understanding the factors associated with IP/IV chemotherapy completion

Dr. DeBernardo explains that although survival benefit has been demonstrated for IP/IV chemotherapy, it is not routinely offered by gynecologic oncologists due to toxicity concerns, port-associated complications and relative treatment complexity. This latest retrospective study aimed to identify the factors associated with treatment non-completion in women with stage III EOC who underwent CRS (<1 cm) followed by IP/IV chemotherapy at Cleveland Clinic from 2000-2016. The study included a total of 96 women, most of whom (>85%) had high-grade serous histology and stage IIIC disease. Pearson χ2 test and 2 sample t-test were used to identify the factors associated with treatment completion.

Sixty-nine of 96 women (71.9%) completed all six cycles of IP/IV chemotherapy. Those women who completed IP/IV chemotherapy had higher rates of home discharge following CRS (92.2% vs. 72.0%) and lower ECOG scores (0 vs. 1.0). The most commonly reported reasons for treatment discontinuation were gastrointestinal (37%), neurologic (22.25) and hematologic (11.1%) adverse events, as well as renal toxicities and port infections (11.1% each).

“The take-home message is that we should still be thinking about giving women with ovarian cancer IP/IV chemotherapy, especially those women who we take to the operating room to remove their cancer upfront,” says Dr. DeBernardo. “[This study] has shown to have the best overall survival (OS) and progression-free survival (PFS) of any study to date. I’d like for clinicians to reconsider IP/IV chemotherapy for their patients, and especially for the subset of patients who are younger, healthier or those who do not need to go to rehab.”

He further emphasizes that it is very important to get IP/IV chemotherapy at a specialized center where physicians have a lot of experience treating ovarian cancer and using this treatment modality.

“We have known for a long time that women treated at inexperienced centers that do not see many ovarian cancer patients don’t fare as well as women who are treated at centers where they have a high volume of patients with this disease,” he says. “Centers of excellence can get people treated with a significantly higher rate of success.”

In conclusion, Dr. DeBernardo notes that the current study had several limitations — one was the retrospective nature of the study that potentially introduced bias in patient selection and the other was inconsistency in IP/IV chemotherapy regimens used in different patients.