The Effect of Using Pazopanib With Food vs. Fasted on Pharmacokinetics, Patient Safety, and Preference (<scp>DIET</scp> Study)

Lubberman, Floor J E; Gelderblom, Hans; Hamberg, Paul; Vervenne, Walter L.; Mulder, Sasja F.; Jansman, Frank G A; Colbers, Angela; Graaf, Winette T.A. van der; Burger, David M.; Luelmo, Saskia; Moes, Dirk Jan A R; Herpen, Carla M.L. van; Erp, Nielka P. van

doi:10.1002/cpt.1515

Cited by 32 publications

(47 citation statements)

References 18 publications

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“…Heath et al demonstrated a higher exposure to pazopanib when administering pazopanib concomitant with food . Thereafter, it was demonstrated that a lower dose of pazopanib can be administered with food while maintaining bio‐equivalent C trough levels of a higher dose without food (n = 78) while gastrointestinal toxicity was comparable when a reduced dose of pazopanib was taken with food . Recently, another study reported that administering pazopanib with food did not increase the risk of toxicity (n = 16), while all but two patients reached adequate C trough.…”

Section: Methodsmentioning

confidence: 99%

“… Not having to fast around the pazopanib intake may positively affect quality of life for cancer patients, especially those experiencing difficulty in maintaining bodyweight. The preference of patients for intake with food was shown in the DIET study where 68% of patients preferred the intake of pazopanib with food compared to without food …”

Section: Methodsmentioning

confidence: 99%

“…131 Thereafter, it was demonstrated that a lower dose of pazopanib can be administered with food while maintaining bio-equivalent C trough levels of a higher dose without food (n = 78) while gastrointestinal toxicity was comparable when a reduced dose of pazopanib was taken with food. 138 Recently, another study reported that administering pazopanib with food did not increase the risk of toxicity (n = 16), while all but two patients reached adequate C trough. 147 Not having to fast around the pazopanib intake may positively affect quality of life for cancer patients, especially those experiencing difficulty in maintaining bodyweight.…”

Section: Food Interventionsmentioning

confidence: 95%

“…The preference of patients for intake with food was shown in the DIET study where 68% of patients preferred the intake of pazopanib with food compared to without food. 138…”

Section: Food Interventionsmentioning

confidence: 99%

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Imatinib, sunitinib and pazopanib: From flat‐fixed dosing towards a pharmacokinetically guided personalized dose

Westerdijk¹,

Desar²,

Steeghs

et al. 2020

Brit J Clinical Pharma

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Tyrosine kinase inhibitors (TKIs) are anti‐cancer drugs that target tyrosine kinases, enzymes that are involved in multiple cellular processes. Currently, multiple oral TKIs have been introduced in the treatment of solid tumours, all administered in a fixed dose, although large interpatient pharmacokinetic (PK) variability is described. For imatinib, sunitinib and pazopanib exposure‐treatment outcome (efficacy and toxicity) relationships have been established and therapeutic windows have been defined, therefore dose optimization based on the measured blood concentration, called therapeutic drug monitoring (TDM), can be valuable in increasing efficacy and reducing the toxicity of these drugs. In this review, an overview of the current knowledge on TDM guided individualized dosing of imatinib, sunitinib and pazopanib for the treatment of solid tumours is presented. We summarize preclinical and clinical data that have defined thresholds for efficacy and toxicity. Furthermore, PK models and factors that influence the PK of these drugs which partly explain the interpatient PK variability are summarized. Finally, pharmacological interventions that have been performed to optimize plasma concentrations are described. Based on current literature, we advise which methods should be used to optimize exposure to imatinib, sunitinib and pazopanib.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Food Interventionsmentioning

confidence: 95%

“…The preference of patients for intake with food was shown in the DIET study where 68% of patients preferred the intake of pazopanib with food compared to without food. 138…”

Section: Food Interventionsmentioning

confidence: 99%

See 2 more Smart Citations

Imatinib, sunitinib and pazopanib: From flat‐fixed dosing towards a pharmacokinetically guided personalized dose

Westerdijk¹,

Desar²,

Steeghs

et al. 2020

Brit J Clinical Pharma

Self Cite

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show abstract

“…3,4 Furthermore, oral absorption of pazopanib is shown to increase when given with food. 5,6 Patients starting with the recommended dosage (800 mg/d without food) often experience discontinuation because of intolerable toxicities. 7 Therefore, it is necessary to develop an individualized dosing strategy for pazopanib therapy.…”

Section: Introductionmentioning

confidence: 99%

Pharmacokinetically guided dosing has the potential to improve real‐world outcomes of pazopanib

Fukudo

Tamaki

Azumi

et al. 2020

Brit J Clinical Pharma

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Dosing Recommendation Based on the Effects of Different Meal Types on Pexidartinib Pharmacokinetics in Healthy Subjects: Implementation of Model‐informed Drug Development Strategy

Zahir

Yin

Hsu

et al. 2023

Clinical Pharm in Drug Dev

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Pexidartinib, an oral small molecule inhibitor of the colony-stimulating factor 1 receptor, is approved for treatment of adults with symptomatic tenosynovial giant cell tumor associated with severe morbidity or functional limitations and not amenable to improvement with surgery. The original dosing regimen is 400 mg of pexidartinib (2 × 200-mg capsules) twice daily, administered on an empty stomach at least 1 hour before or 2 hours after a meal or snack. Because pexidartinib is likely to be taken over an extended period of time, the ability to take pexidartinib with a meal would simplify timing of administration and potentially improve compliance. Since administering 400 mg of pexidartinib with a low-fat meal increases exposure by ≈60% relative to the fasted state, administering 250 mg of pexidartinib with a low-fat meal (low-fat meal dosing regimen) was predicted to achieve an exposure similar to 400 mg administered during a fasted state (original dosing regimen). Based on clinical trial simulations with two one-sided t-tests and bootstrapping (ie, resampling) analyses, a bioequivalence study (n = 24) would have >90% power to conclude that the original dosing regimen (400 mg fasted twice daily) and the low-fat meal dosing regimen (250 mg with a low-fat meal twice daily) are bioequivalent. This report provides the outcome of the implementation of the model-informed drug development strategy to recommend and justify a low-fat meal dosing regimen for pexidartinib that has the potential to improve patient compliance while maintaining drug exposure.

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The Effect of Using Pazopanib With Food vs. Fasted on Pharmacokinetics, Patient Safety, and Preference (DIET Study)

Cited by 32 publications

References 18 publications

Imatinib, sunitinib and pazopanib: From flat‐fixed dosing towards a pharmacokinetically guided personalized dose

Imatinib, sunitinib and pazopanib: From flat‐fixed dosing towards a pharmacokinetically guided personalized dose

Pharmacokinetically guided dosing has the potential to improve real‐world outcomes of pazopanib

Dosing Recommendation Based on the Effects of Different Meal Types on Pexidartinib Pharmacokinetics in Healthy Subjects: Implementation of Model‐informed Drug Development Strategy

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