Concomitant Use of Proton Pump Inhibitors With Capecitabine Based Neoadjuvant Chemoradiotherapy for Locally Advanced Rectal Cancer

Abstract

Aim: Capecitabine (Cape) is routinely used for the neoadjuvant chemoradiation treatment (NACRT) of locally advanced rectal cancers (LARCs). Previous reports have suggested that the concomitant use of proton pump inhibitors (PPIs) may affect the efficacy of Cape, although the true effect of PPIs when used with Cape as a radiosensitizer for neoadjuvant radiation is unclear. The aim of our study was to evaluate the impact of concurrent PPI use along with fluorouracil (FU) and Cape based NACRT in terms of pathologic and oncological outcomes, in patients with LARC.Methods: LARC patients treated at our center with NACRT from 2010 to 2016 were identified. Postoperative pathology and follow-up outcomes were examined for any differences with relation to the use of PPIs concurrently with FU and Cape based NACRT and adjuvant chemotherapy regimens.Results: Three hundred four and 204 patients received treatment with FU and Cape based NACRT. No difference in pathologic complete response rate was noted between the 2 arms with the concurrent use of PPIs (25.8% and 25%, respectively, P = 0.633); or with and without the use of PPIs in the Cape-NACRT arm specifically (20% and 20.7%, P = 0.945). At a median follow-up of 5 years, no statistical difference in local or distant control was noted in the Cape-NACRT patients, with and without concomitant PPI use (P = 0.411 and 0.264, respectively). Multivariate analysis showed no association of PPI use and NACRT with Cape, in terms of local control (hazard ratio = 0.001, P = 0.988) or overall survival (hazard ratio = 1.179, confidence interval = 0.249-5.579, P = 0.835).Conclusions: Our study revealed that there was no adverse pathologic or oncological outcome with the concurrent use of PPIs along with Cape-NACRT in the treatment of LARC. We report that it may be safe to use PPIs if essential, in this clinical setting, although it would be wise to exercise caution.

Influence of proton pump inhibitors on the pathological response of rectal cancer: a multicentre study

“…The frequency of PPI intake in this study (20.3% for the capecitabine cohort and 26.5% for the 5-FU cohort) is in line with the literature, which describes gastric acid inhibitors use from 23.5% to 36.9% in colorectal cancer patients [18,19] The studies that evaluated potential DDI between PPI and capecitabine/5-FU in gastrointestinal tumours presented conflicting results [14,[20][21][22][23][24][25][26][27][28]. Chu et al [13] reported the detrimental effect of PPI in progression-free and overall survival in patients treated with CAPOX, but not CAPOX + lapatinib for metastatic gastric cancer.…”

“…Specifically in rectal cancer, three retrospective studies evaluated the effects of PPI and fluoropyrimidines during neoadjuvant chemoradiotherapy. Menon et al [ 21 ] did not find differences in pathological response or survival in relation to PPI use, both in capecitabine and 5-FU cohorts. Similar findings were observed in a retrospective French cohort of patients treated with neoadjuvant capecitabine + radiotherapy [ 27 ].…”

Proton pump inhibitors display anti‐tumour potential in glioma

“…In the clinic, PPIs have been proven the ability to overcome the resistance of conventional chemotherapeutic drugs for breast cancer and radiation. The use of PPIs in 6754 patients suffering from breast cancer significantly not only improved the overall survival rate of these patients and reduced the disease recurrence rate but overcome the resistance of conventional chemotherapy drugs and radiation 303 . Besides, based on clinical epidemiological comparative trials, PPIs can assist radiotherapy and chemotherapy to delay the overall survival of 206 patients with rectal cancer 56 .…”

Re-thinking the possible interaction between proton pump inhibitors and capecitabine

“…In a study of 508 locally advanced rectal cancer patients receiving either capecitabine or 5-FU based neoadjuvant chemoradiation (NACRT) [ 11 ], concomitant PPI use was 9.8% and 10.2 in both groups respectively. There was no significant effect of PPI use on disease-free survival and OS for capecitabine-based NACRT.…”

“…The inconsistency between studies described above, was highlighted in a systematic review [ 2 ], which included nine of the fourteen studies listed above, but did not include more recent publications [ 7 , 8 , 10 , 11 , 13 ]. We have briefly summarised the outcomes reported in these twelve studies for either capecitabine or 5-FU (Table 1 ).…”