Effects of Proton Pump Inhibitors Intake During Chemoradiotherapy for Rectal Cancer: a Retrospective Cohort Study.

PURPOSE: Proton pump inhibitors (PPIs) are one of the most widely used drugs worldwide and are involved in several drug interactions. Recently, several studies have suggested that PPIs may interfere with the efficacy of capecitabine. This study primarily aimed to investigate the effects of PPI intake on the pathologic response rate of patients with locally advanced rectal cancer treated with neoadjuvant chemoradiotherapy with capecitabine. METHOD: A retrospective study was conducted at a French Comprehensive Cancer Center. Patients with locally advanced rectal cancer treated with neoadjuvant chemoradiotherapy followed by surgery were included in the study. Demographic parameters, treatment characteristics, survival data, and PPI intake data were collected. Frequencies and percentages were reported for categorical variables and medians and interquartile ranges for continuous variables. Distribution of variables was compared according to PPI treatment using the chi-square test or Fisher's exact test for categorical data and nonparametric Wilcoxon tests for continuous variables. Survival data were estimated using the Kaplan-Meier method and compared using the log-rank test. RESULTS: In total, 215 patients were included, of whom 135 (62.8%) were men. The PPI intake frequency was 16.1%. The rate of complete pathological response was not significantly lower in patients on PPIs than in those not on PPIs (8.7% vs. 19%, p = 0.36). PPI intake was not associated with a statistically significant decrease in recurrence-free survival (hazard ratio [HR] = 1.26, 95% confidence interval [CI] 0.61-2.60, p = 0.54) or overall survival (HR = 0.95, 95% CI 0.33-2.76, p = 0.93). CONCLUSION: No significant association was observed between PPI co-medication and complete pathological response or survival in patients treated for locally advanced rectal cancer. However, the safety of PPIs could not be confirmed. Further ancillary studies of prospective clinical trials or studies using the Health Data Hub are necessary to explore the effects of PPIs on rectal cancer more accurately.

Preserving bone in cancers of the elderly: A necessity.

The occurrence of bone fractures is frequent in the elderly population, and in cancer patients, especially with bone metastases. The growing incidence of cancer associated with an aging population implies important health challenges, including bone health. Decisions on cancer care in older adults have to take into account older adults' specificities. Screening tools as G8 or VES 13 and evaluating tools as comprehensive geriatric assessment (CGA) do not include bone-related items. Bone risk assessment is indicated according to identification of geriatric syndromes such as falls, history, and the oncology treatment plan. Some cancer treatments disrupt bone turnover and decrease bone mineral density. This is mainly caused by hypogonadism, induced by hormonal treatments and some chemotherapies. Treatments can also cause direct (i.e., chemotherapy, radiotherapy or glucocorticoids) or indirect toxicity through electrolyte disorders (i.e., some chemotherapies or tyrosine kinase inhibitors) on bone turnover. Bone risk prevention is multidisciplinary. Certain interventions proposed in the CGA aim to improve bone health and reduce the risk of falling. It is also based on the drug management of osteoporosis, and the prevention of complications from bone metastases. Management of fractures, related or not to bone metastases relates to the concept of orthogeriatrics. It is also based on the benefit-risk ratio of the operation, access to minimally invasive techniques, prehabilitation or rehabilitation, but also the prognosis related to cancer and geriatric syndromes. Bone health is essential in older cancer patient's care. Bone risk assessment should be part of CGA in routine use and specific decision-making tools should be developed. Bone event management must be integrated throughout the patient's care pathway and oncogeriatrics multidisciplinarity should include rheumatological expertise.

Proton Pump Inhibitors and Cancer: Current State of Play.

Background: Proton pump inhibitors (PPIs) are one of the most widely used drugs worldwide and are overprescribed in patients with cancer; there is increasing evidence of their effects on cancer development and survival. The objective of this narrative review is to comprehensively identify cancer medications that have clinically meaningful drug-drug interactions (DDIs) with PPIs, including loss of efficacy or adverse effects, and to explore the association between PPIs and cancer. Methods: A PubMed search of English language studies published from 1 January 2016, to 1 June 2021 was conducted. The search terms included "proton pump inhibitors," "cancer," "chemotherapy," "immunotherapy," "hormonotherapies," "targeted therapies," "tyrosine kinase inhibitors," and "gut microbiome". Recent and relevant clinical trials, meta-analyses, and reviews were included. Results: PPIs may have pro-tumor activity by increasing plasma gastrin levels or anti-tumor activity by inhibiting V-ATPases. However, their impact on cancer survival remains unclear. PPIs may decrease the efficacy of some antineoplastic agents through direct DDIs (e.g., some tyrosine kinase inhibitors, capecitabine, irinotecan, methotrexate). More complex DDIs seem to exist for immunotherapies with indirect interactions through the microbiome. PPIs worsen hypomagnesemia, bone loss, iron, and vitamin B12 deficiencies but may have a protective effect on the renal system. Discussion/Conclusions: PPIs may interact with the cancer microbiome and the efficacy of various antineoplastic agents, although only a few DDIs involving PPIs are clinically significant. Further pharmaco-epidemiological studies are warranted, but physicians should be aware of the potential consequences of PPI use, which should be dose appropriate and prescribed according to guidelines.