Effects of Proton Pump Inhibitors on FOLFOX and CapeOx Regimens in Colorectal Cancer (original) (raw)
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Journal of Clinical Oncology, 2022
130 Background: Tyrosine kinase inhibitors (TKI) are the most common oral drugs in cancer patients. Similarly, proton pump inhibitors (PPI) are commonly used to relieve dyspeptic symptoms in patients with cancer. However, gastric pH levels may affect the absorption of TKI through the gastrointestinal system. However, all TKIs do not have the same chemical structure, and the absorption rate of each TKI depends on their solubility in different gastric pH levels. Limited data is available about the clinical outcomes of concomitant use of PPI and regorafenib in patients with metastatic colorectal cancer (mCRC). We present here the results of the multicenter study following the initial results of our single-center experience. Methods: Patients with mCRC treated with regorafenib were included in this multicenter and retrospective study. Patients prescribed PPI after initiation of regorafenib were assigned to the PPI user group, and the remaining patients were assigned to the PPI non-user ...
JAMA oncology, 2016
Capecitabine is an oral cytotoxic chemotherapeutic commonly used across cancer subtypes. As with other oral medications though, it may suffer from drug interactions that could impair its absorption. To determine if gastric acid suppressants such as proton pump inhibitors (PPIs) may impair capecitabine efficacy. This secondary analysis of TRIO-013, a phase III randomized trial, compares capecitabine and oxaliplatin (CapeOx) with or without lapatinib in 545 patients with ERBB2/HER2-positive metastatic gastroesophageal cancer (GEC); patients were randomized 1:1 between CapeOx with or without lapatinib. Proton pump inhibitor use was identified by medication records. Progression-free survival (PFS) and overall survival (OS) were compared between patients treated with PPIs vs patients who were not. Specific subgroups were accounted for, such as younger age (<60 years), Asian ethnicity, female sex, and disease stage (metastatic/advanced) in multivariate Cox proportional hazards modeling...
Proton Pump Inhibitor Intake During Chemoradiotherapy for Rectal Cancer: A Retrospective Study
2021
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 pathological 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 radiochemotherapy followed by surgery were included in the study. Demographic parameters, treatment characteristics, survival data, and PPI intake data were collected. 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 complet...
Long-Term Use of Proton Pump Inhibitors in Cancer Patients: An Opinion Paper
Cancers, 2022
Multikinase inhibitors (MKIs), and particularly tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors (CPIs), are currently some of the major breakthroughs in cancer treatment. Proton pump inhibitors (PPIs) revolutionised the treatment of acid-related diseases, but are frequently overused for epigastric pain or heartburn. However, long-term acid suppression from using PPIs may lead to safety concerns, and could have a greater impact in cancer patients undergoing therapy, like bone fractures, renal toxicities, enteric infections, and micronutrient deficiencies (iron and magnesium). Moreover, acid suppression may also affect the pharmacokinetics of drugs (at least during acid suppression) and decrease the absorption of many molecularly-targeted anticancer therapies, which are mostly weak bases with pH-dependent absorption. This type of drug-drug interaction may have detrimental effects on efficacy, with major clinical impacts described for some orally administrated target...
Oxaliplatin plus oral fluoropyrimidines in colorectal cancer
Clinical colorectal cancer, 2004
The medical treatment of colorectal cancer (CRC) has rapidly evolved in recent years with the introduction of novel cytotoxic drugs into clinical practice such as irinotecan, oxaliplatin, and capecitabine. Combination regimens using infusional 5-fluorouracil (5-FU)/leucovorin (LV) plus either oxaliplatin or irinotecan have demonstrated clinically meaningful, high efficacy in advanced CRC. Based on the results of the Intergroup trial N9741, FOLFOX4, a combination of infusional plus bolus 5-FU/LV and oxaliplatin, has emerged as the standard first-line therapy in the palliative setting. However, infusional 5-FU-based regimens carry the need for use of central venous lines and implantable ports to allow treatment on an outpatient basis and are thus inconvenient and expensive. The use of oral fluoropyrimidines (capecitabine or uracil/tegafur [UFT] plus LV) as substitutes for infusional 5-FU in combination protocols with oxaliplatin offers greater convenience, at the same time conceivably...
Cancers
Background: In recent years, proton pump inhibitors (PPIs) have been investigated at high-dose to modulate tumor microenvironment acidification thus restoring chemotherapeutic sensitivity. This is the first trial to study activity and safety of repurposing high dose rabeprazole combined with metronomic capecitabine (mCAP). Methods: A phase II study in which patients with gastrointestinal cancer, refractory to standard treatments, who had a life expectancy >3 months, were blind randomized 1:1 to mCAP, 1500 mg/daily, continuously with or without rabeprazole 1.5 mg/kg bid, three days a week. The primary endpoint was 3-months progression-free survival (PFS). The secondary endpoints were clinical benefit (CB) and overall survival (OS). Safety and plasma concentrations of capecitabine and its metabolites (5′-DFUR and 5-FU) were also evaluated. Results: Sixty-seven (median age 69 years; 63% male; 84% colorectal cancer, 76% ECOG-PS ≤ 1; 84% pretreated with two or more lines of chemothera...
Evidence-based support for the use of proton pump inhibitors in cancer therapy
Journal of Translational Medicine, 2015
We can only cure what we can understand first' , said Otto H. Warburg, the 1931 Nobel laureate for his discovery on tumor metabolism. Unfortunately, we still don't know too much the mechanisms underlying of cancer development and progression. One of the unsolved mystery includes the strategies that cancer cells adopt to cope with an adverse microenvironment. However, we knew, from the Warburg's discovery, that through their metabolism based on sugar fermentation, cancer cells acidify their microenvironment and this progressive acidification induces a selective pressure, leading to development of very malignant cells entirely armed to survive in the hostile microenvironment generated by their own metabolism. One of the most mechanism to survive to the acidic tumor microenvironment are proton exchangers not allowing intracellular acidification through a continuous elimination of H + either outside the cells or within the internal vacuoles. This article wants to comment a translational process through which from the preclinical demonstration that a class of proton pump inhibitors (PPI) exploited worldwide for peptic ulcer treatment and gastroprotection are indeed chemosensitizers as well, we have got to the clinical proof of concept that PPI may well be included in new anti-cancer strategies, and with a solid background and rationale.
Journal of Clinical Oncology, 2005
Purpose We performed this phase III study to compare the irinotecan, leucovorin (LV), and fluorouracil (FU) regimen (FOLFIRI) versus the oxaliplatin, LV, and FU regimen (FOLFOX4) in previously untreated patients with advanced colorectal cancer. Patients and Methods A total of 360 chemotherapy-naive patients were randomly assigned to receive, every 2 weeks, either arm A (FOLFIRI: irinotecan 180 mg/m2 on day 1 with LV 100 mg/m2 administered as a 2-hour infusion before FU 400 mg/m2 administered as an intravenous bolus injection, and FU 600 mg/m2 as a 22-hour infusion immediately after FU bolus injection on days 1 and 2 [LV5FU2]) or arm B (FOLFOX4: oxaliplatin 85 mg/m2 on day 1 with LV5FU2 regimen). Results One hundred sixty-four and 172 patients were assessable in arm A and B, respectively. Overall response rates (ORR) were 31% in arm A (95% CI, 24.6% to 38.3%) and 34% in arm B (95% CI, 27.2% to 41.5%; P = .60). In both arms A and B, median time to progression (TTP; 7 v 7 months, respe...