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Progression-free survival increased with FOLFOX4 and surgery
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Patients with liver metastases from colorectal cancer may experience a lower risk of events of progression-free survival with surgery and perioperative chemotherapy with the FOLFOX4 regimen, compared with surgery alone.
In a parallel-group study, researchers from various institutes in Europe randomly assigned 364 patients with up to four liver metastases from colorectal cancer to either six cycles of FOLFOX4 before and after surgery (n=182) or to surgery alone (n=182). The FOLFOX4 regimen includes oxaliplatin (Eloxatin, Sanofi-Aventis), 5-Fluorouracil and leucovovin.
After a median of six preoperative cycles, 151 patients (83%) in the perioperative chemotherapy cohort were resected and 115 (63%) received a median of six postoperative cycles. In the surgery group, 152 patients (84%) were resected, according to the abstract.
In randomized patients, the rate of increase in progressive-free survival after three years was 7.3% (28.1% to 35.4%); in eligible patients, 8.1% (28.1% to 36.2%) and in resected patients, 9.2% (33.2% to 42.4%).
Death occurred in 139 patients (64 in the perioperative chemotherapy group and 75 in the surgery group). Those in the chemotherapy group experienced more reversible postoperative complications, compared with the surgery alone group. – by Stacey L. Adams
Lancet. 2008;371:1007-1016.
This is a very important clinical trial showing for the first time that perioperative chemotherapy is associated with a better outcome for patients with initially resectable liver metastases from colon cancer. There has been little doubt that patients whose disease was not resectable should undergo chemotherapy and if the tumor responded and became resectable, that surgery improved outcome. There is ongoing controversy about whether patients who have initially resectable disease should receive chemotherapy prior to the resection, or if they should undergo resection right away.
Neoadjuvant and adjuvant chemotherapy/perioperative chemotherapy showed a reduction of progression-free survival in the eligible and resected patients. These data suggest that patients with resectable liver lesions should be considered for perioperative chemotherapy. The oncologists usually prefer chemotherapy in the neoadjuvant setting allowing them to evaluate the efficacy of chemotherapy, and patients who respond or have stable disease have a better surgical outcome. Surgeons are usually hesitant because they are afraid tumors may grow under chemotherapy and those that are resectable will become unresectable. However, if a tumor grows aggressively under chemotherapy, the tumor is aggressive and it is unlikely that earlier surgery would have been successful.
– Heinz-Josef Lenz, MD
Associate Director, Norris Gastrointestinal Oncology
Program
University of Southern California