Abstract 498P
Background
The association between capecitabine efficacy and coadministration of proton pump inhibitors (PPIs) has currently been controversial issue. The present study aimed to clarify whether coadministration of PPIs affects the real-world effectiveness of capecitabine in postoperative patients with early-stage colorectal cancer (CRC) receiving adjuvant chemotherapy.
Methods
In this multicenter, retrospective, observational study, patients with stage II-III CRC who were treated with adjuvant capecitabine monotherapy or CapeOX regimen (capecitabine and oxaliplatin) between 2009 and 2014 were collected from the medical records of nine institutions in Japan. Patients were divided into the two groups which were treated with or without coadministration of PPIs. Relapse free survival (RFS) and Overall survival (OS) were evaluated as a primary and secondary endpoint, respectively. Multivariable Cox proportional hazards models (MVA), propensity score-adjusted (PSA), and inverse probability of treatment weighting (IPTW) analyses were used.
Results
Data of 606 patients were evaluated in the study. Of these patietns, 54 patients received PPIs (8.9%). The median duration of follow-up was 5.9 years (max: 10.9 years). There were 125 relapse events and 74 deaths in both groups combined. MVA showed PPI group had poor RFS (HR 1.45, 95% CI; 0.83–2.53; P = 0.192) and poor OS (HR 1.19, 95% CI; 0.56–2.53; P = 0.656) than patients not treated with PPIs. Especially, HR for RFS with capecitabine monotherapy was 2.07 (95% CI; 1.03–4.15; P = 0.041). Sensitivity analyses using PSA and IPTW analyses for both RFS and OS demonstrated consistent results. Table: 498P
RFS in stage II-III CRC
| Variables | MVA | PSA | IPTW | |||
| HR (95% CI) | P Value | HR (95% CI) | P Value | HR (95% CI) | P Value | |
| PPI (Yes) | 1.45 (0.83–2.53) | 0.192 | 1.46 (0.84–2.54) | 0.185 | 1.64 (0.89–3.02) | 0.112 |
| Age (10-years intervals) | 0.93 (0.79–1.10) | 0.406 | ||||
| Sex (Male) | 1.39 (0.97–1.99) | 0.077 | ||||
| Primary site (Right-sided colon) | 1.29 (0.88–1.90) | 0.192 | ||||
| Stage (III) | 1.20 (0.67–2.14) | 0.543 | ||||
| Regimen (CapeOX) | 1.25 (0.84–1.87) | 0.265 |
Conclusions
The findings suggest that concomitant use of PPIs may reduce the effectiveness of capecitabine and negatively impact survival outcomes for patients with stage II–III CRC.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.