Adjuvant chemotherapy delivered directly to the liver via an implanted hepatic artery infusion (HAI) pump is associated with improved survival in colorectal cancer patients following complete resection of liver metastases, a new study shows.
Use of adjuvant HAI chemotherapy in such patients, given in addition to adjuvant systemic chemotherapy, “was strongly associated with much better survival” than use of adjuvant systemic chemotherapy alone, senior author Dr. Michael I. D’Angelica told Reuters Health by email.
“The average improvement in overall survival was 2 years,” noted Dr. D’Angelica, of Memorial Sloan Kettering Cancer Center in New York City.
Resection for limited colorectal-cancer liver metastases is potentially curative, but the majority of patients experience recurrent disease and most die. Studies of adjuvant systemic chemotherapy to improve outcomes after resection have been “disappointing,” with no demonstration of improved survival, Dr. D’Angelica said.
Because the hepatic artery provides most of the blood supply to the liver, which has a high “first-pass extraction” of chemotherapy drugs such as floxuridine, using an HAI pump to deliver such drugs makes it possible to deliver a high dosage to the liver with little systemic exposure.
However, adjuvant HAI chemotherapy has not been widely adopted, even though some studies have suggested that it offers a survival advantage following resection. One reason is that earlier studies “were performed before the introduction of modern systemic therapy such as oxaliplatin and irinotecan,” Dr. D’Angelica and colleagues say.
The current study analyzed data from a database with information on all patients who underwent complete resection of colorectal liver metastases from 1992 to 2012 at Memorial Sloan Kettering Cancer Center. Patients who received adjuvant HAI chemotherapy also received preoperative and/or adjuvant systemic chemotherapy.
Characteristics and outcomes of 1,583 patients (67%) who were treated without HAI chemotherapy were compared with those of 785 patients (33%) who received the treatment. Median follow-up of survivors was 55 months.
Even though patients who received HAI chemotherapy had more advanced disease, their median overall survival was longer than those who did not (67 months vs. 44 months; p<0 .001="" 20.="" april="" clinical="" in="" journal="" of="" oncology="" online="" p="" report="" researchers="" the="">
Both five-year and 10-year overall survival rates were significantly greater among those who received adjuvant HAI chemotherapy (about 53% vs. 38% at five years and about 38% vs. 24% at 10 years; p<0 .001="" both="" comparisons="" for="" p="">0>
Receiving HAI was associated with longer survival in both “early” (1992 to 2002) and “late” (2003 to 2012) eras, the latter reflecting the emergence of modern systemic chemotherapy. Median overall survival was 60 months vs. 40 months during the early era, and 72 months vs. 51 months during the late era, with or without HAI, respectively.
Propensity-score analysis to match patients for seven known prognostic factors also found longer overall survival with perioperative HAI (hazard ratio, 0.67; p<0 .001="" p="">0>
“The strong association was independent of the use of modern systemic chemotherapy and remained in propensity score analysis,” the researchers noted.
Subgroup analyses found that patients with node-negative primary tumors or a low clinical risk score (reflecting a combination of prognostic factors such as the number and size of metastases) appeared to benefit the most from HAI chemotherapy.
Dr. D’Angelica said he was not surprised by improved survival in patients who received HAI chemotherapy.
“We have seen dramatically improved outcomes with adjuvant hepatic-artery chemotherapy for a long time now,” he said. “This was the first study, however, that had adequate numbers of patients and follow-up to perform a complete comparative analysis.”
The new study “provides data that strongly supports investment (in) a definitive multicenter randomized controlled trial that would definitively test this concept,” Dr. D’Angelica said.
The inclusion of 10-year overall survival, which essentially equates with cure in this patient population (38% in patients treated with HAI chemotherapy vs. 24% in those treated without), is one of the study’s strengths, Dr. Paul J. Karanicolas, of the Edmond Odette Cancer Centre at Sunnybrook Health Sciences Centre in Toronto, Canada, told Reuters Health by email.
These “impressive results” are despite the fact that the patients who received HAI chemotherapy generally had more advanced disease, with a higher likelihood of recurrence, noted Dr. Karanicolas, who was not involved in the current study.
“One surprising finding . . . is that patients with earliest disease, measured with the clinical risk score, seemed to benefit the most from the treatment,” he said.
Dr. Karanicolas said that applying the results of this study to practice presents a challenge, because HAI chemotherapy requires expertise in hepatobiliary surgery, medical oncology, interventional radiology, nuclear medicine, and nursing.
“It should only be offered in the context of an established multidisciplinary program with expertise in all of these areas,” he said.
The study had no commercial funding, and the authors reported no disclosures.
J Clin Oncol 2017.0>