Safety of neoadjuvant oxaliplatin-based chemotherapy (N-FOLFOX) in patients undergoing resection of colorectal liver metastases (R-CLM). Interim results

Abstract

14550 Background: Oxaliplatin-5-fluorouracil-leucovorin (FOLFOX) has significant activity against CRC in both the metastatic and adjuvant settings. Consequently, neoadjuvant FOLFOX (N-FOLFOX) is being investigated in R-CLM. This has raised concerns regarding the safety and rate of post-operative complications (P-OCs) with N-FOLFOX, specifically, development of sinusoidal dilatation (SD), fibrosis and steatosis. This single-center cohort study was conducted to prospectively evaluate safety of N-FOLFOX in R-CLM patients. Methods: Planned total sample size is 40 patients [20 N-FOLFOX; 20 no chemotherapy (N-C)]. The N-C group consists of patients undergoing surgery for other hepatic pathology. Normal liver was examined by light (LM) and electron (EM) microscopy for SD, perisinusoidal fibrosis, and steatosis/necrosis; severity was graded from 0 (absent) to 2. The rate of P-OCs, hospital stays, and liver function tests (LFTs) were assessed. Results: At the time of this analysis, 20 patients (10 N-FOLFOX; 10 N-C) have undergone surgery. In the N- FOLFOX group, median number of cycles of N-FOLFOX was 6, with 2 patients receiving only 4 cycles. The median time between completion of N-FOLFOX and surgery was 6 weeks. There were no statistical differences between N-FOLFOX and N-C groups in potentially confounding factors, including previous chemotherapy, alcohol consumption, medical history, or concomitant medications. Number of patients with SD was 8 in each group (all were grade 1 except for 1 patient in N-C who had grade 2). Steatosis was seen in 7 and 6 patients in N-FOLFOX, and N-C groups, respectively (2 patients in each group were grade 2; remaining were grade 1). Fibrosis was noted in only 1 patient in N-C group. No nodular regeneration was observed in either group. There was a subjective loss on EM of mitochondria and Golgi apparatus/body with N-FOLFOX. Median post-operative hospital stay was 12 days in both groups. Conclusions: N-FOLFOX appears to have no clinically significant deleterious effects on normal liver architecture, function, or recovery post-surgery in R-CLM patients. The study is ongoing to accrue up to 40 patients; updated data will be presented. No significant financial relationships to disclose.