Real‐world outcomes for neoadjuvant capecitabine versus infusional 5‐fluorouracil in the treatment of locally advanced rectal cancer

Abstract

Background Neoadjuvant chemoradiation therapy is standard‐of‐care treatment for locally advanced rectal cancer (LARC). A pathological complete response (pCR) following chemoradiation therapy is an early indicator of treatment benefit and associated with excellent survival outcomes, with capecitabine largely replacing infusional 5‐fluorouracil as the choice in routine care of LARC. Aims To analyse the uptake of capecitabine usage over time, and on the back of clinical trial data demonstrating equivalence between fluoropyrimidines, confirm that efficacy is maintained in the real‐world setting. Methods We analysed data from a prospectively maintained colorectal cancer database at three Australian hospitals including patients diagnosed from January 2009 to December 2018. Pathological response was determined as either complete or incomplete and compared for patients receiving 5‐FU or capecitabine. Results A total of 657 patients was analysed, 498 receiving infusional 5‐FU and 159 capecitabine. Capecitabine use has markedly increased from approval in 2014 in Australia, now being used in more than 80% of patients. Patient characteristics were similar by treatment, including age, tumour location and pre‐treatment stage. pCR was reported in 22/159 (13.8%) of capecitabine‐treated patients and 118/380 (23.7%) that received 5‐FU (P ≤ 0.01). More capecitabine‐treated patients received post‐operative oxaliplatin (44.2% vs 6.3%, P < 0.01). Two‐year progression‐free survival was similar (84.9% vs 88.0%, P = 0.34). Conclusions Capecitabine is now the dominantly used neoadjuvant chemotherapy in LARC. Capecitabine use was associated with a lower rate of pCR versus infusional 5‐FU, a difference not explained by examined patient or tumour characteristics. Poor treatment compliance with oral therapy in the real‐world setting is one possible explanation.

Neoadjuvant capecitabine in rectal cancer chemoradiotherapy: too early to ring the alarms

“…We read with great interest the remarkable study by Loft et al, comparing capecitabine or 5-fluorouracil (FU)'s efficacy in the neoadjuvant chemoradiotherapy of rectal cancer in a real-life setting. 1 The authors observed significantly decreased complete pathological response (pCR) rates with the capecitabine, which was rather unexpected. As shown in the study, capecitabine largely replaced 5-FU in the chemoradiotherapy of rectal cancer with the convenience of oral use and comparable efficacy.…”

“…As shown in the study, capecitabine largely replaced 5-FU in the chemoradiotherapy of rectal cancer with the convenience of oral use and comparable efficacy. 1,2 The authors pointed out the relative lack of data comparing 5-FU and capecitabine in the modern era, 1 with only one recent study from Australia identifying the inferior outcomes with capecitabine. 3 We agree with the authors' concerns and thank them for giving a perspective on this important issue.…”

“…3 We agree with the authors' concerns and thank them for giving a perspective on this important issue. To evaluate this problem further, we separately meta-analysed the studies published before [4][5][6][7][8][9] or after 2010 1,3,[10][11][12] and saw decreased pCR rates with capecitabine in studies published after 2010 (Fig. 1A,B, hazards ratio (HR): 1.64, 95% confidence interval (CI): 1.17-2.31 vs HR: 0.65, 95% CI: 0.45-0.93).…”

“…1D, HR: 0.49, 95% CI: 0.31-0.77). 1,3 Additionally, the two studies from Australia 1,3 were the reason for the decreased pCR rates in studies published after 2010. We think that this difference could stem from biological features or, more likely, from healthcare-related issues like different out-of-pocket costs impairing capecitabine compliance between the Far-East and Australia, as seen in other oral anti-cancer agents.…”