Survival Impact of CAPOX Versus FOLFOX in the Adjuvant Treatment of Stage III Colon Cancer

Abstract

Background: Capecitabine and oxaliplatin (CAPOX) and folinic acid, fluorouracil, and oxaliplatin (FOLFOX) are both used in the adjuvant treatment of colon cancer, and while their efficacy is assumed to be similar, they have not been directly compared. We reviewed the toxicity profiles, relative dose intensity (RDI), and survival associated with these regimens across a multi-institutional cohort.

Patients and methods: We identified 394 consecutively treated patients with stage III colon cancer who received an oxaliplatin-containing regimen. RDI was defined as the total dose received divided by the intended total dose if all cycles were received.

Results: FOLFOX was associated with increased mucositis (6.2% vs. 0.7%, P = .0069) and neutropenia (25.9% vs. 8.6%, P < .0001), while CAPOX was associated with increased dose-limiting toxicities (DLTs) (90.7% vs. 80.2%, P = .0055), diarrhea (31.8% vs. 9.0%, P < .0001), and hand-foot syndrome (19.9% vs. 2.1%, P < .0001). Higher median RDI of fluoropyrimidine (93.7% vs. 80.0%, P < .0001) and oxaliplatin (87.2% vs. 76.3%, P < .0001) was noted for patients receiving FOLFOX. Reducing the duration from 6 to 3 months would have prevented 28.7% of FOLFOX and 20.5% of CAPOX patients from ever experiencing a DLT (P = .0008). Overall survival did not differ by regimen (hazard ratio = 0.73; 95% confidence interval 0.45-1.22; P = .24). However, CAPOX was associated with improved disease-free survival (3-year disease-free survival 83.8% vs. 73.4%, P = .022), which remained significant in high-risk (T4 or N2) (P = .039) but not low-risk patients (P = .19).

Conclusion: CAPOX may be associated with improved disease-free survival despite greater toxicities and lower RDI. Reducing adjuvant chemotherapy duration to 3 months would prevent 26% of patients from ever experiencing a DLT.

Keywords: Colorectal; Dose intensity; Duration; Toxicity; XELOX.