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 targeted therapies (erlotinib, gefitinib, pazopanib, palbociclib), and conflicting results with many others, including capecitabine. Furthermore, the long-term use of PPIs results in severe alterations to the gut microbiome and recent retrospective analyses have shown that the benefit of using CPIs was suppressed in patients treated with PPIs. These very expensive drugs are of great importance because of their efficacy. As the use of PPIs is not essential, we must apply the precautionary principle. All these data should encourage medical oncologists to refrain from prescribing PPIs, explaining to patients the risks of interaction in order to prevent inappropriate prescription by another physician.

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SOC System Organ Class (SOC), the highest level of the MedDRA 1 hierarchy, is identified by anatomical or physiological system, etiology, or purpose (e.g., SOC Investigations for laboratory test results). CTCAE terms are grouped by MedDRA Primary SOCs. Within each SOC, AEs are listed and accompanied by descriptions of severity (Grade). CTCAE Terms An Adverse Event (AE) is any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medical treatment or procedure that may or may not be considered related to the medical treatment or procedure. An AE is a term that is a unique representation of a specific event used for medical documentation and scientific analyses. Each CTCAE v4.0 term is a MedDRA LLT (Lowest Level Term). Grades Grade refers to the severity of the AE. The CTCAE displays Grades 1 through 5 with unique clinical descriptions of severity for each AE based on this general guideline: Grade 1 Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated. Grade 2 Moderate; minimal, local or noninvasive intervention indicated; limiting ageappropriate instrumental ADL*. Grade 3 Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care ADL**. Grade 4 Life-threatening consequences; urgent intervention indicated. Grade 5 Death related to AE. A Semicolon indicates 'or' within the description of the grade. A single dash (-) indicates a Grade is not available. Not all Grades are appropriate for all AEs. Therefore, some AEs are listed with fewer than five options for Grade selection. Grade 5 Grade 5 (Death) is not appropriate for some AEs and therefore is not an option. Definitions A brief Definition is provided to clarify the meaning of each AE term. A single dash (-) indicates a Definition is not available. Navigational Notes A Navigational Note is used to assist the reporter in choosing a correct AE. It may list other AEs that should be considered in addition to or in place of the AE in question. A single dash (-) indicates a Navigational Note has not been defined for the AE term. Activities of Daily Living (ADL) *Instrumental ADL refer to preparing meals, shopping for groceries or clothes, using the telephone, managing money, etc. **Self care ADL refer to bathing, dressing and undressing, feeding self, using the toilet, taking medications, and not bedridden. 1 CTCAE v5.0 incorporates certain elements of the MedDRA terminology. For further details on MedDRA refer to the MedDRA MSSO Web site (https://www.meddra.org/).