Does gastric acid suppression affect sunitinib efficacy in patients with advanced or metastatic renal cell cancer?

Ha, Vincent; Ngo, Margaret; Chu, Michael P.; Ghosh, Sunita; Sawyer, Michael B.; Chambers, Carole

doi:10.1177/1078155214527145

Cited by 45 publications

(46 citation statements)

References 10 publications

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“…Ha et al showed that in 231 patients with renal clear cell carcinoma the association of Sunitinib and PPIs was related with shorter progression-free and overall survival (Ha et al, 2015). Similarly, in a series of 507 lung cancer patients undergoing treatment with Erlotinib, the concomitant administration of PPIs was related with shorter progression-free and overall survival .…”

Section: Interaction Of Ppi With Oral Anticancer Agentsmentioning

confidence: 99%

Proton Pump Inhibitors in cancer patients: How useful they are? A review of the most common indications for their use

Numico

Fusco

Franco

et al. 2017

Critical Reviews in Oncology/Hematology

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Section: Interaction Of Ppi With Oral Anticancer Agentsmentioning

confidence: 99%

Proton Pump Inhibitors in cancer patients: How useful they are? A review of the most common indications for their use

Numico

Fusco

Franco

et al. 2017

Critical Reviews in Oncology/Hematology

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“…Most importantly, acid-inhibitory drugs, such as proton pump inhibitors (PPIs), increase the intragastric pH, which may decrease the solubility and thereby the biological availability of certain TKIs. Although there are no prospective studies available, some retrospective data clearly showed that PPI use was associated with decreased TKI efficacy [5–7]. …”

Section: Introductionmentioning

confidence: 99%

Tyrosine Kinase Inhibitors and Proton Pump Inhibitors: An Evaluation of Treatment Options

et al. 2017

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Tyrosine kinase inhibitors (TKIs) have rapidly become an established factor in oncology, and have been shown to be effective in a wide variety of solid and hematologic malignancies. Use of the oral administration route of TKIs offers flexibility and is convenient for the patient; however, despite these advantages, the oral route of administration also causes a highly relevant new problem. Acid-inhibitory drugs, such as proton pump inhibitors (PPIs), increase the intragastric pH, which may subsequently decrease TKI solubility, bioavailability, and treatment efficacy. Clear and practical advice on how to manage PPI use during TKI therapy is currently not available in the literature. Since PPIs are extensively used during TKI therapy, prescribers are presented with a big dilemma as to whether or not to continue the combined treatment, resulting in patients possibly being deprived of optimal therapy. When all pharmacological characteristics and data of either TKIs and PPIs are considered, practical and safe advice on how to manage this drug combination can be given.

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“…128 Gastrointestinal adverse effects of sunitinib may potentiate the use of proton pump inhibitors. 126 However, acidsuppressing agents are suspected to decrease absorption and hence its efficacy. 126,142 Food does not significantly influence sunitinib's bioavailability.…”

Section: Pharmacogenetic And/or Drug-induced Changes In Metabolizing mentioning

confidence: 99%

“…126 However, acidsuppressing agents are suspected to decrease absorption and hence its efficacy. 126,142 Food does not significantly influence sunitinib's bioavailability. 154 The effect of acid-reducing agents on the absorption of both vandetanib and venurafenib has not been studied, but based on solubility data is anticipated to be insignificant.…”

Section: Pharmacogenetic And/or Drug-induced Changes In Metabolizing mentioning

confidence: 99%

“…These bind irreversibly to hydrogen potassium ATPase pumps and may elevate gastric luminal pH to as high as pH 7. 125 The duration of PPI-induced gastric acid suppression [125][126][127][128] may potentially be sustained for several days after therapy cessation. 129 Coadministration of an acid-reducing agent may markedly impair systemic absorption of many of the molecularly targeted agents (which exhibit pHdependent solubility), 128 potentially causing suboptimal tumor exposure and development of drug resistance pathways.…”

Section: Comedication Usementioning

confidence: 99%

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Pharmacokinetic‐Guided Dosing of New Oral Cancer Agents

Lucas

Martin

2017

The Journal of Clinical Pharma

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Generally, licensed drug-dosing recommendations for chemotherapy are based on results from clinical trials in which subjects are usually of relatively normal body size, middle-aged, and are relatively racially homogeneous, with minimal comorbidity and specific tumor characteristics. Very few nontrial patients meet these characteristics, resulting in clinical practice having to extrapolate dosing recommendations to the specific patient. There is insufficient research on the impact of obesity-associated physiological changes prevalent in patients with common cancers on standard pharmacokinetic and pharmacodynamic parameters. Yet quantifying the influence of obesity on the pharmacology of chemotherapy is vital, as dosing inappropriate for body composition (ie, flat dosing or mg/kg based on total body weight) may increase the risk of adverse events and reduce clinical effectiveness. Unfortunately, there are few cancer guidelines to aid clinicians in selecting the optimal dose in the obese-even recent guidelines are based predominantly on clinical opinion/current practice in treating obese patients, rather than evidence. Data in many other vulnerable groups, for example, those with significant comorbidity and older patients, are also scarce. Because of the known limitations of body surface area-guided dosing, therapeutic drug monitoring or pharmacokinetic-guided dosing, which predicts an individual's exposure, has increasingly been shown to be a powerful tool in cancer therapy. Used appropriately, it can adjust for differences in pharmacokinetic parameters not considered when body size-based dosing or "one dose fits all" is used. This review will focus predominantly on the rationale for pharmacokinetic-guided dosing of the newer oral molecularly targeted antineoplastics in people whose drug exposure is not predicted by their physiology or body composition.

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Does gastric acid suppression affect sunitinib efficacy in patients with advanced or metastatic renal cell cancer?

Abstract: There was a significant difference in progression-free survival and overall survival between the acid suppressed and no acid suppression groups. Further research is required to confirm this potential interaction.

Cited by 45 publications

References 10 publications

Proton Pump Inhibitors in cancer patients: How useful they are? A review of the most common indications for their use

Proton Pump Inhibitors in cancer patients: How useful they are? A review of the most common indications for their use

Tyrosine Kinase Inhibitors and Proton Pump Inhibitors: An Evaluation of Treatment Options

Pharmacokinetic‐Guided Dosing of New Oral Cancer Agents

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