The association between capecitabine efficacy and proton pump inhibitors (PPIs) is controversial. Here, we determined whether co-administration of PPIs affects the real-world effectiveness of capecitabine. This retrospective observational study included consecutive patients with stage II–III colorectal cancer (CRC) who received adjuvant capecitabine monotherapy or CapeOX (capecitabine and oxaliplatin) between January 2009 and December 2014 at nine participating institutions. The primary endpoint was the difference in relapse-free survival (RFS) between patients who received PPIs and those who did not and was estimated using the Kaplan–Meier method. Overall survival (OS) was the secondary endpoint. Multivariable analysis of RFS and OS was performed using a Cox proportional hazards model, propensity score adjustment, and inverse probability of treatment weighting (IPTW) analyses. Data from 606 patients were evaluated, 54 of whom had received a PPI. PPI-treated patients tended to have poorer RFS and OS than patients treated without PPIs. The hazard ratio for RFS with capecitabine monotherapy was 2.48 (95% confidence interval: 1.22–5.07). These results were consistent with sensitivity analyses performed using propensity score adjustment and IPTW methods. Co-administration of PPIs may reduce the effectiveness of capecitabine and negatively impact patients with stage II–III CRC.
Background and Aims: Cancer-specific glycosylation plays an important role in the development and progression of cancer. Epigenetics may contribute to forming cancer-specific glycosylation by regulating the expression of glycogenes. Although comprehensive analysis of epigenetics is routinely performed, comprehensive glycan analysis, especially using human clinical samples, has been limited due to technical underdevelopment. Our aims are to understand the significance of glycosylation and its epigenetic regulation on renal carcinogenesis and to identify cancer-specific glycosylation as a potential diagnostic marker and a novel therapeutic target. Materials and Methods: Comprehensive glycomics and methylome analysis were performed by lectin microarray and Infinium HumanMethylation450 BeadChip on 50 non-cancerous renal cortex tissue (N) and 50 clear cell renal cell carcinoma (RCC) (T) microdissected from formalin-fixed and paraffin-embedded tissue samples. Results: Compared to N samples, T samples showed higher fluorescence intensity for lectins recognizing mannose-type glycans, and lower intensity for lectins recognizing sialyl and fucosyl groups. In RCC, the metabolism of N-glycans may remain in an immature state. By hierarchical clustering using lectin microarray data, T samples were divided into Clusters A and B with significant differences in patients’ outcome. Increased high-mannose type N-glycan and core fucosylation and decreased sialylation were observed in T samples of Cluster A. According to these results, glycosylation profiles showed heterogeneity associated with patients’ outcome among RCCs, and immature N-glycan may be specific in some RCCs. Methylome analysis suggests that specific glycosylation profiles of RCCs may be induced by DNA methylation alteration on glycogenes. Association between DNA methylation and mRNA expression was confirmed on some glycogenes using real-time reverse transcription PCR. As a result of examining whether the signal intensity pattern of each lectin reflects the prognosis of clear cell RCC, we could identify the lectins that reflect the RCCs prognosis. Conclusion: In RCC, the metabolism of N-glycans may remain in an immature state. The glycan profiles show heterogeneity among individual RCCs, and some of the specific glycan profiles may be associated with patients’ outcome. Cancer-specific glycan profiles may be regulated by epigenetic alteration of glycogenes. Citation Format: Yoshiko Kitazume, Eri Arai, Atsushi Matsuda, Kentaro Ohara, Akiko Miyagi Maeshima, Teruhiko Yoshida, Atsushi Kuno, Yae Kanai. Cancer-specific glycosylation regulated by epigenomic alteration in renal cell carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5702.
Background:The association between the effectiveness of capecitabine and the concomitant administration of gastric acid suppressants remains controversial. We aimed to clarify whether the effectiveness of capecitabine is affected by the co-administration of histamine H2 receptor antagonists (H2RAs) in early-stage colorectal cancer (CRC) patients using real-world data. Methods: This multicenter, retrospective, observational study included consecutive patients with stage II-III CRC who received either capecitabine monotherapy or the CapeOX regimen (capecitabine and oxaliplatin) as adjuvant therapy between January 2009 and December 2014 in Japan. Relapse-free survival (RFS) and overall survival were estimated using the Kaplan-Meier method. Additionally, multivariable Cox proportional hazards model, propensity score adjustment, and inverse probability of treatment weighting analyses were performed. Results: In total, 552 patients were included in this study, of which 30 were co-administered H2RAs. RFS at five years was 76.7% (95% confidence interval [CI]: 57.2-88.1%) and 79.8% (95% CI: 76.0-83.0%) in the H2RA and non-H2RA groups, respectively. Multivariable Cox proportional hazards model and propensity score-adjusted analyses showed that the co-administration of H2RAs was associated with a poor RFS among those receiving capecitabine monotherapy (hazard ratio [HR], 2.01; 1.81; respectively). In contrast, these results were inconsistent with the group receiving the CapeOX regimen. Conclusions:The study findings suggest that the co-administration of H2RAs may not reduce the effectiveness of capecitabine therapy in patients with early-stage CRC. To confirm this relationship, a prospective study with a pharmacokinetic approach is needed.
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