Cost-Neutral Optimization of Pazopanib Exposure by Splitting Intake Moments: A Prospective Pharmaco*kinetic Study in Cancer Patients (2024)

Dutch Pharmacology Oncology Group (DPOG) (2020). Cost-Neutral Optimization of Pazopanib Exposure by Splitting Intake Moments: A Prospective Pharmaco*kinetic Study in Cancer Patients. Clinical Pharmaco*kinetics, 59(7), 941-948. https://doi.org/10.1007/s40262-020-00863-5

Dutch Pharmacology Oncology Group (DPOG). / Cost-Neutral Optimization of Pazopanib Exposure by Splitting Intake Moments : A Prospective Pharmaco*kinetic Study in Cancer Patients. In: Clinical Pharmaco*kinetics. 2020 ; Vol. 59, No. 7. pp. 941-948.

@article{0a78213f93e44c7a9eedeb6692bd8bc0,

title = "Cost-Neutral Optimization of Pazopanib Exposure by Splitting Intake Moments: A Prospective Pharmaco*kinetic Study in Cancer Patients",

abstract = "BACKGROUND AND OBJECTIVE: Pazopanib is an oral tyrosine kinase inhibitor used in the treatment of renal cell carcinoma and soft-tissue sarcoma. At the approved dose of 800 mg once daily (QD), 16-20% of patients are being underdosed and at risk of decreased efficacy. This study aimed to show whether splitting intake moments, as a cost-neutral alternative to a dose increase, leads to an increased exposure.METHODS: We performed a cross-over trial comparing the pharmaco*kinetics of pazopanib 800 mg QD with pazopanib 400 mg twice daily. Pharmaco*kinetic sampling was performed at steady-state for both dosing schedules.RESULTS: Nine evaluable patients were included. At the 800 mg QD dosing schedule, median minimum plasma concentration (Cmin), area under the concentration-time curve from 0 to 24 h (AUC0-24h), and maximum plasma concentration (Cmax) were 23.2 mg/L (interquartile range 18.5-27.6), 773 mg h/L (557-1009), and 40.6 mg/L (36.4-56.4) compared with 41.6 mg/L (30.5-55.8, p = 0.004), 942 mg h/L (885-1419, p = 0.027), and 50.2 mg/L (46.8-72.5, p = 0.074) at 400 mg twice daily. One patient experienced a grade 3 event (i.e., diarrhea).CONCLUSIONS: This study demonstrates that splitting intake moments of pazopanib leads to a 79% increase in Cmin, with acceptable tolerability. Therefore, this new dosing schedule offers a cost-neutral opportunity to optimize treatment in patients with low exposure.CLINICAL TRIAL REGISTRATION: NL6137 ( http://www.trialregister.nl ).",

author = "{Dutch Pharmacology Oncology Group (DPOG)} and Groenland, {Stefanie L} and {van Eerden}, {Ruben A G} and Verheijen, {Remy B} and {de Vries}, Niels and Bas Thijssen and Hilde Rosing and Beijnen, {Jos H} and Koolen, {Stijn L W} and Mathijssen, {Ron H J} and Huitema, {Alwin D R} and Neeltje Steeghs",

year = "2020",

month = jul,

doi = "10.1007/s40262-020-00863-5",

language = "English",

volume = "59",

pages = "941--948",

journal = "Clinical Pharmaco*kinetics",

issn = "0312-5963",

publisher = "Adis International Ltd",

number = "7",

}

Dutch Pharmacology Oncology Group (DPOG) 2020, 'Cost-Neutral Optimization of Pazopanib Exposure by Splitting Intake Moments: A Prospective Pharmaco*kinetic Study in Cancer Patients', Clinical Pharmaco*kinetics, vol. 59, no. 7, pp. 941-948. https://doi.org/10.1007/s40262-020-00863-5

Cost-Neutral Optimization of Pazopanib Exposure by Splitting Intake Moments: A Prospective Pharmaco*kinetic Study in Cancer Patients. / Dutch Pharmacology Oncology Group (DPOG).
In: Clinical Pharmaco*kinetics, Vol. 59, No. 7, 07.2020, p. 941-948.

Research output: Contribution to journal › Article › Academic › peer-review

TY - JOUR

T1 - Cost-Neutral Optimization of Pazopanib Exposure by Splitting Intake Moments

T2 - A Prospective Pharmaco*kinetic Study in Cancer Patients

AU - Dutch Pharmacology Oncology Group (DPOG)

AU - Groenland, Stefanie L

AU - van Eerden, Ruben A G

AU - Verheijen, Remy B

AU - de Vries, Niels

AU - Thijssen, Bas

AU - Rosing, Hilde

AU - Beijnen, Jos H

AU - Koolen, Stijn L W

AU - Mathijssen, Ron H J

AU - Huitema, Alwin D R

AU - Steeghs, Neeltje

PY - 2020/7

Y1 - 2020/7

N2 - BACKGROUND AND OBJECTIVE: Pazopanib is an oral tyrosine kinase inhibitor used in the treatment of renal cell carcinoma and soft-tissue sarcoma. At the approved dose of 800 mg once daily (QD), 16-20% of patients are being underdosed and at risk of decreased efficacy. This study aimed to show whether splitting intake moments, as a cost-neutral alternative to a dose increase, leads to an increased exposure.METHODS: We performed a cross-over trial comparing the pharmaco*kinetics of pazopanib 800 mg QD with pazopanib 400 mg twice daily. Pharmaco*kinetic sampling was performed at steady-state for both dosing schedules.RESULTS: Nine evaluable patients were included. At the 800 mg QD dosing schedule, median minimum plasma concentration (Cmin), area under the concentration-time curve from 0 to 24 h (AUC0-24h), and maximum plasma concentration (Cmax) were 23.2 mg/L (interquartile range 18.5-27.6), 773 mg h/L (557-1009), and 40.6 mg/L (36.4-56.4) compared with 41.6 mg/L (30.5-55.8, p = 0.004), 942 mg h/L (885-1419, p = 0.027), and 50.2 mg/L (46.8-72.5, p = 0.074) at 400 mg twice daily. One patient experienced a grade 3 event (i.e., diarrhea).CONCLUSIONS: This study demonstrates that splitting intake moments of pazopanib leads to a 79% increase in Cmin, with acceptable tolerability. Therefore, this new dosing schedule offers a cost-neutral opportunity to optimize treatment in patients with low exposure.CLINICAL TRIAL REGISTRATION: NL6137 ( http://www.trialregister.nl ).

AB - BACKGROUND AND OBJECTIVE: Pazopanib is an oral tyrosine kinase inhibitor used in the treatment of renal cell carcinoma and soft-tissue sarcoma. At the approved dose of 800 mg once daily (QD), 16-20% of patients are being underdosed and at risk of decreased efficacy. This study aimed to show whether splitting intake moments, as a cost-neutral alternative to a dose increase, leads to an increased exposure.METHODS: We performed a cross-over trial comparing the pharmaco*kinetics of pazopanib 800 mg QD with pazopanib 400 mg twice daily. Pharmaco*kinetic sampling was performed at steady-state for both dosing schedules.RESULTS: Nine evaluable patients were included. At the 800 mg QD dosing schedule, median minimum plasma concentration (Cmin), area under the concentration-time curve from 0 to 24 h (AUC0-24h), and maximum plasma concentration (Cmax) were 23.2 mg/L (interquartile range 18.5-27.6), 773 mg h/L (557-1009), and 40.6 mg/L (36.4-56.4) compared with 41.6 mg/L (30.5-55.8, p = 0.004), 942 mg h/L (885-1419, p = 0.027), and 50.2 mg/L (46.8-72.5, p = 0.074) at 400 mg twice daily. One patient experienced a grade 3 event (i.e., diarrhea).CONCLUSIONS: This study demonstrates that splitting intake moments of pazopanib leads to a 79% increase in Cmin, with acceptable tolerability. Therefore, this new dosing schedule offers a cost-neutral opportunity to optimize treatment in patients with low exposure.CLINICAL TRIAL REGISTRATION: NL6137 ( http://www.trialregister.nl ).

U2 - 10.1007/s40262-020-00863-5

DO - 10.1007/s40262-020-00863-5

M3 - Article

C2 - 32020530

SN - 0312-5963

VL - 59

SP - 941

EP - 948

JO - Clinical Pharmaco*kinetics

JF - Clinical Pharmaco*kinetics

IS - 7

ER -

Dutch Pharmacology Oncology Group (DPOG). Cost-Neutral Optimization of Pazopanib Exposure by Splitting Intake Moments: A Prospective Pharmaco*kinetic Study in Cancer Patients. Clinical Pharmaco*kinetics. 2020 Jul;59(7):941-948. doi: 10.1007/s40262-020-00863-5