Results from a recent phase 3 clinical trial show that a specialized type of chemotherapy delivery may delay disease recurrence in newly diagnosed, advanced ovarian cancer patients.
The specialized technique, called hyperthermic intraperitoneal chemotherapy (HIPEC), involves warming the chemotherapy to temperatures greater than 42.0°C (107.6°F) and circulating it through the abdominal cavity directly after surgery.
In this multi-center randomized clinical trial (NCT00426257), physicians compared outcomes for patients who received HIPEC after tumor-debulking surgery to patients who had surgery alone. The study, “Hyperthermic Intraperitoneal Chemotherapy in Ovarian Cancer,” was published in New England Journal of Medicine.
Directly delivering chemotherapy to the area affected by cancer concentrates the drug in the area where its killing effects will be more beneficial, which can make it more effective. Increasing the temperature of the chemotherapy has been shown to make it easier for the drug to penetrate the lining of the abdomen, and the heat makes cancer cells more susceptible to damage. Additionally, targeted delivery can decrease some of the toxic side effects associated with standard treatment, which spreads the chemotherapy throughout the entire body.
However, intraperitoneal chemotherapy is not widely accepted as part of the standard of care for ovarian cancer, and the approach has been somewhat controversial in the medical community.
To take a closer look at the efficacy of HIPEC, physicians enrolled 245 ovarian cancer patients who were scheduled to undergo tumor-debulking surgery. All patients had received three cycles of chemotherapy prior to surgery.
Participants were randomized to undergo HIPEC plus surgery or surgery alone. After surgery, all patients also received additional cycles of chemotherapy following standard-of-care practices.
After a median follow-up time of 4.9 years, 85% of patients had either died or experienced a recurrence of their cancer. However, women who underwent surgery plus HIPEC went 3.5 months longer without cancer recurrence compared to women who underwent surgery alone — 14.2 months compared with 10.7 months.
Women who underwent surgery plus HIPEC had 62% chance of survival at three years, while the group who underwent surgery alone had a 48% chance. The chance of a woman being recurrence-free at three years was more than double if she received HIPEC along with surgery — 17% versus 8%.
Importantly, the addition of HIPEC to tumor-debulking surgery did not significantly affect the rate of severe or life-threatening adverse events. This shows that the treatment is reasonably safe.
Although this study provides compelling data regarding the efficacy of HIPEC, Drs. David Spriggs and Oliver Zivanovic, from the Memorial Sloan Kettering Cancer Center, wrote an accompanying editorial pointing out that there are still many unanswered questions about this specialized delivery of chemotherapy.
For example, they noted that it is still not clear exactly why or how HIPEC is leading to improved outcomes: Is it due to the regional delivery of the chemotherapy, or is it the increased temperature? Does delivering chemotherapy during the surgery provide the added benefits, compared to postoperative chemotherapy?
Spriggs and Zivanovic write that future clinical trials are necessary to begin to answer these questions. “This randomized trial is a very important first step but should not drive changes in practice yet,” they conclude.