Roisin E. O'Cearbhaill, MD
Dennis S. Chi, MD
Memorial Sloan Kettering Cancer Center
New York, NY
Approximately 22,000 women will be diagnosed with epithelial ovarian cancer (EOC) in the United States in 2014, making it the nation’s second most common gynecologic malignancy.1
The cancer, which often presents at an advanced stage, causes more deaths than any other type of gynecologic malignancy.
Current standard treatment for EOC is a combination of surgery and platinum-based chemotherapy. Although most patients initially respond to treatment, the majority of them eventually develop resistance to platinum therapy, and the cancer recurs. Long-term cure rates languish between 20 and 30 percent.
An important and unique characteristic of ovarian cancer is that it tends to recur within, and remain confined to, the abdominal (peritoneal) cavity for most of its natural history, rather than spreading to distant organs. Once a recurrence in the peritoneal cavity is diagnosed, the disease is no longer curable, and median progression-free survival is six to nine months.
Prevention of disease progression and improvement of treatment strategies are therefore of utmost importance.Clinical Trials
Because the peritoneal cavity is the predominant site of disease, local intraperitoneal (IP) drug delivery has been evaluated in randomized clinical trials.2-4
These trials compared standard intravenous (IV) chemotherapy to cisplatin-based IP therapy delivered through an IP access device after postoperative recovery (several weeks after surgery).
In a 2006 trial, 2 a statistically significant increase in the median progression-free and overall survival was recorded for the cisplatin/paclitaxel IP treatment compared to the IV group, with a survival benefit of 6 and 16 months, respectively. However, a substantial percentage of patients were unable to complete the planned six cycles of cisplatin/paclitaxel IP chemotherapy, in most cases due to abdominal discomfort following postoperative adhesion barriers and IP catheter-related complications.2
Hyperthermic Intraoperative Intraperitoneal Chemotherapy (HIPEC)
HIPEC differs from traditional postoperative IP delivery primarily in terms of timing (it is administered as a one-time dose in the operating room at the time of cytoreductive surgery) and heating of the antineoplastic drug (Figure 1).
The local therapeutic strategy has been explored in the treatment of other solid tumors, including pseudomyxoma peritonei and appendiceal and colorectal cancers,5 both of which have a similar propensity for peritoneal spread as EOC.
Proposed advantages of the intraoperative, single- dose approach include controlled intraoperative drug exposure without the barriers of postoperative adhesions. In addition, hyperthermia has been shown to increase tumor penetration of anticancer drugs and to synergistically enhance cyotoxicity of platinum agents.
Similar to postoperative IP treatment, the approach is most effective in patients with minimal residual disease after cytoreductive surgery. In contrast to established experience with postoperative normothermic IP treatment, prospective studies on HIPEC in EOC are scant.
In short, surgical cytoreduction with HIPEC is a rational but still experimental approach in the management of EOC.Next Steps
Memorial Sloan Kettering researchers are currently exploring the combination of surgical tumor resection and HIPEC with platinum agents in patients with recurrent ovarian cancer. An initial small pilot study showed HIPEC to be safe.6