Key Takeaways;
- Hepatic artery infusion (HAI) pumps are used at many hospitals to treat people with advanced colorectal cancer that has spread to the liver.
- The use of HAI pumps involves risks and uncertainties that suggest more research is needed.
- Dana-Farber researchers recommend more clinical trials of HAI pumps to help doctors and patients make evidence-based decisions about their therapy choices.
Researchers in the late 1970s wanted to address challenges with a chemotherapy drug called floxuridine. It’s a form of chemotherapy invented in the 1950s that turns into its active form, 5-fluorouracil, or 5-FU, when metabolized.
One challenge is that 5-FU has off-target effects, meaning it can damage healthy organs when given throughout the body. In addition, much of the drug is cleared by the liver before it has a chance to be effective.
Their solution was a hepatic artery infusion (HAI) pump, which is surgically implanted into the abdomen. It infuses chemotherapy directly into the liver via a catheter inserted into the hepatic artery. This artery carries the primary blood supply for tumors in the liver. The solution aims to get more drug into the cancer with fewer off-target effects.
“It’s a great concept,” says Benjamin L. Schlechter, MD, a medical oncologist in gastrointestinal cancer at Dana-Farber. “But good ideas don’t always make good medicine.”
Surgeons and oncologists have been using HAI pumps based on clinical trials conducted in the 1980s. They typically use the pumps to treat patients with advanced colorectal cancer who have liver tumors that are too large for surgery. A common goal is to shrink the tumors so they can be removed surgically. That goal, according to those who use the therapy, is often reached.
But not without risk and uncertainty.
Schlechter and his colleagues at Dana-Farber urge caution. They advocate for more clinical trials to truly understand how HAI pumps perform compared to modern chemotherapy. They also recommend trials to better understand which patients the intervention might benefit most.
“Modern chemotherapy and targeted medicines are much more effective than they were a few decades ago. You cannot use the older data showing that this intervention is an effective treatment in the era of modern therapy,” says Schlechter. “This therapy could be superior for some patients, but it needs to be proven in a clinical trial.”
What are the risks and uncertainties?
Risk of infection. The HAI pump is inserted into the abdomen, where it will stay for months or years. All surgery comes with risks, but abdominal surgery has an elevated risk of bacterial infection. If the pump becomes infected, that infection can spread into the liver and put the patient at risk of severe illness or death. In some cases, the pump insertion surgery is done at the same time as the surgery to remove the primary tumor in the colon. This combination further raises the risk of life-threatening bacterial infection. Without carefully reviewed clinical trial data for many patients across multiple sites, it is difficult to estimate how common infections after HAI pump surgery are.
Risk of shortchanged systemic therapy. An HAI pump’s infusion of chemotherapy into the liver is not sufficient to treat all of the cancer. For patients with advanced colorectal cancer, the cancer is a full body disease and requires systemic treatment. However, the use of the HAI pump may put a limit on the use of the systemic chemotherapy that can treat the disease elsewhere in the body such as the lymph nodes and lungs. Without comparison of the options in a clinical trial — for simplicity, for example, comparing modern systemic chemotherapy vs. chemotherapy plus an HAI pump — it is not clear which option is most beneficial for patients. HAI may add benefit, but it that’s not certain. It may add risk that is greater than the benefit. It could even have no benefit at all.
Uncertainty about the best suited patient population. Clinical evidence does suggest that for most patients, liver tumors shrink with the use of this therapy. But the bigger question is whether or not the use of an HAI pump improves overall survival and health of patients compared with modern standard therapy. The question is a complex one. The answer could be that it depends on certain features of the cancer, the patient, the surgical decisions, or something else. Clinical trials would help doctors and patients make evidence-based decisions about their therapy choices.
About the Medical Reviewer
Dr. Schlechter is a medical oncologist who specializes in gastrointestinal cancers including colorectal cancer, anal cancer, pancreatic cancer, and neuroendocrine cancers, among others. He is a former intern, resident, chief resident and fellow at Beth Israel Deaconess Medical Center as well as a member of the faculty at Harvard Medical School. In the past he was the Director of Inpatient Hematology and Oncology at Beth Israel Deaconess Medical Center as well as the Assistant Program Director of the Internal Medicine Residency Program. His work at Dana-Farber focuses on providing excellent patient care while trying to advance the treatment of gastrointestinal cancer patients.