A procedure called hyperthermic (heated) intraperitoneal chemotherapy, or HIPEC, has shown some promise in early studies for certain types of cancer. Although a number of hospitals in the country are now offering HIPEC, the data to support its use is limited, and some experts argue that more research is needed to evaluate the risks and benefits of the approach, which patients are most likely to benefit, and whether it is better than standard therapies.
Now experts at Memorial Sloan Kettering have set out to attain conclusive scientific evidence to determine the effectiveness of HIPEC in patients with colorectal or appendix cancer, and in women with certain gynecologic cancers.
HIPEC is based on a related approach that involves the delivery of unheated chemotherapy directly into the lining of the abdominal area, known as the peritoneal cavity, through a surgically implanted catheter. This technique allows a high concentration of medication to reach the area where the cancer was surgically removed in order to treat residual cancer cells. Pioneered at Memorial Sloan Kettering, the technique — known as intraperitoneal chemotherapy (IPC) — has been shown in several trials to extend survival among patients with certain cancers when delivered in the days or weeks following surgery.
Heating Chemotherapy to Boost Effect
Laboratory evidence suggests that heat makes cancer cells more sensitive to certain chemotherapy agents and may improve the ability of those drugs to penetrate and kill cancer cells more efficiently. During HIPEC, surgeons heat chemotherapy to around 107 degrees Fahrenheit and infuse it into the peritoneal cavity immediately after surgery is completed.
“This approach allows surgeons to give higher doses of anticancer drugs than they can intravenously, directly exposing any remaining cancer cells to a ‘bath’ of chemotherapy,” says gynecologic surgeon Oliver Zivanovic. “However, it is not an insignificant procedure, adding another two hours of time in the operating room while the patient is under anesthesia.”
Risks and Benefits of HIPEC
HIPEC has been studied in patients with appendix cancer, peritoneal mesothelioma, colorectal cancer, uterine cancer, and ovarian cancer — solid tumors with a similar propensity to spread to the peritoneal lining. Some studies have reported complications such as decreased white blood cell count, anemia, low platelets, gastrointestinal issues, and neuropathy, a nerve problem that causes pain, numbness, tingling, swelling, or muscle weakness.
On the other hand, because HIPEC delivers cancer drugs directly to the area where microscopic cancer cells may persist, and only a small portion of a given drug is absorbed into the blood stream, side effects such as nausea are minimal compared to those that can occur with multiple cycles of traditional, intravenous chemotherapy. In addition, a number of early studies have shown HIPEC to be safe. One trial conducted in Europe demonstrated a survival advantage of surgery with HIPEC compared to systemic chemotherapy alone among patients with colorectal cancer.
At Memorial Sloan Kettering, HIPEC is offered to patients only within the context of clinical studies. A specially trained team of experienced surgeons, nurses, and anesthesiologists works together to safely administer the treatment, operate the equipment, and monitor the patient. Radiologists are also involved to ensure the careful review of radiologic images taken before and after surgery.
“A number of US hospitals have begun offering HIPEC as a treatment option outside of the clinical trial setting based on positive data from small studies evaluating a single group of patients without a control group for comparison,” says Dr. Zivanovic, who is Director of Innovative Surgical Technology at Memorial Sloan Kettering. “Rather than extrapolating from those results, we have chosen to carefully study this approach in randomized clinical trials.”
Studying HIPEC for Gynecologic Cancers
Memorial Sloan Kettering is the first cancer center in the United States to offer a randomized clinical trial to study HIPEC in women who are having surgery for a recurrence of ovarian, fallopian tube, or peritoneal cancer. The study — in which patients are arbitrarily assigned to one of two treatment groups and followed prospectively over time — is helping researchers learn which approach provides the best balance of safety and effectiveness.
“This phase II study will provide the most reliable, unbiased information about whether HIPEC really does make a difference in the outcomes of patients with these cancers,” says gynecologic surgeon Dennis S. Chi.
Half of the patients will receive HIPEC followed by five cycles of intravenous chemotherapy after the surgery. The other half will receive six cycles of postoperative intravenous chemotherapy. Investigators will follow patients for two years after the treatment to compare the incidence of recurrence and side effects between the two groups.
“It is important to understand which patients are most likely to benefit from HIPEC and whether it is as good or better than standard therapy based on how long they remain free of disease progression. If the results support it, we will be able to confidently recommend HIPEC as a treatment option for these patients,” adds Dr. Chi, who is the principal investigator of the study.
Exploring Effectiveness in Colorectal and Appendix Cancers
Memorial Sloan Kettering is also offering a randomized, phase II clinical trial comparing HIPEC to EPIC in patients with metastatic colorectal cancer or appendix cancer. It will be the first-ever prospective trial of any treatment for patients with appendix cancer worldwide, and the first randomized trial of IP chemotherapy for patients with colorectal cancer in the United States.
Patients will be randomly assigned to one of two groups to receive either HIPEC at the time of surgery or early postoperative intraperitoneal chemotherapy (EPIC), which is delivered for three days immediately following surgery. Researchers will compare the number of patients in each group who remain free of disease recurrence after three years and compare complication rates and changes in the quality of life of the patients undergoing each treatment. They will also collect tumor tissue to identify unique genetic markers that may make the cancers more sensitive to certain treatments, including the chemotherapies used in the trial and other types of drugs.
“Our goal is to have a balanced trial that will determine which of these treatments is superior and provide information we need to guide future patient management,” says oncologic surgeon Garrett M. Nash, who is leading the trial.
“If our findings show that HIPEC is safe and effective, we may have an opportunity to explore whether the effectiveness of other types of treatments such as targeted drugs and immune therapies can also be enhanced using this approach,” adds Dr. Zivanovic.