ASCOFOLFOX4 given before and after resection of colorectal cancer liver metastases can significantly reduce the risk of recurrence, according to final data from the first study to test this approach. At the plenary session of the American Society of Clinical Oncology 43rd Annual Meeting, Bernard Nordlinger, MD, reported the findings on behalf of the European Organization for Research and Treatment of Cancer (EORTC) study 40983 investigators (abstract 5).
"This treatment should be proposed as the new standard for these patients, and, very importantly, should be delivered by a multidisciplinary team," said Dr. Nordlinger, professor of surgery and chairman of the Department of Surgery and Oncology at Ambroise Paré Hospital, Boulogne, France.
The study, known as EPOC, included many major European cancer centers. Investigators enrolled 364 patients who had colorectal cancer and up to four liver metastases, with no extrahepatic metastases. More than 90% of patients had less than four lesions.
Patients were randomized between perioperative FOLFOX4 (oxaliplatin [Eloxatin] 85 mg/m2 and LV/5-FU2 every 2 weeks), six cycles before and six cycles after surgery (n = 182), and surgery alone (n = 182). The rationale for preoperative chemotherapy, he said, is that tumor response allows resection of smaller metastases and testing of their chemo-responsiveness. The rationale for postoperative chemotherapy is that dormant cancer cells are present in remnant liver and that chemotherapy has been shown to be beneficial in stage III colon cancer. "This was a pragmatic approach, and the design was not meant to validate the value of postoperative vs preoperative chemotherapy," Dr. Nordlinger added.
Eleven patients in each arm were ineligible because they did not meet the criteria for randomization. The primary study endpoint was progression-free survival (PFS), and the investigators hoped to increase median PFS by 40% (HR 0.71).
Compliance with preoperative chemotherapy was "excellent," Dr. Nordlinger said, with almost 80% of patients receiving six cycles. Tolerance was "as expected," he said, with 8% grade 3 diarrhea, 2% grade 3 neuropathy, and 18% grade 3-4 neutropenia. "One patient was not resected due to liver damage probably induced by chemotherapy," he said. Lesion size decreased by nearly 30% during preoperative chemotherapy, from a median sum of the largest diameters of 45 mm before treatment to 30 mm after treatment, "thus allowing surgeons to resect smaller tumors," he said. The complete response rate was 3.8%, partial response 40.1%, and stable disease 35.2%.
After various exclusions (mostly because of being inoperable due to advanced disease), 151 patients in the chemotherapy group and 152 in the control group were able to undergo resection. Among the chemotherapy group, 115 started postoperative chemotherapy.