Does dose modification affect efficacy of first-line pazopanib in metastatic renal cell carcinoma?

Grassi, Paolo; Procopio, Giuseppe; Ratta, Raffaele; Porcu, Luca; Martinetti, Antonia; Mennitto, Alessia; Verzoni, Elena

doi:10.1200/jco.2017.35.6_suppl.512

Cited by 2 publications

(1 citation statement)

References 7 publications

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“…In patients with severe hypoalbuminemia, we would be concerned if the total pazopanib concentration may be misinterpreted as a falsely lower exposure to free active pazopanib than what was reflected in the patient. Thus, our findings had provided greater depth to interpret free drug concentration of pazopanib in the event of therapeutic drug monitoring [17,18,19,20] and could allow physiologically based pharmacokinetic models to be built. There could be potential use of albumin levels to complement laboratory liver function tests to guide clinicians in dosage adjustments such as using lower doses to minimise drug-use related adverse events.…”

Section: Effect Of Variable Albumin Levels In Human Plasma On Fu% Of Pazopanibmentioning

confidence: 98%

HPLC-MS/MS coupled with equilibrium dialysis method for quantification of free drug concentration of pazopanib in plasma

Toh

Pang

Shwe

et al. 2020

Heliyon

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Background: The selective occurrence of hepatotoxicity observed with use of pazopanib may be attributed to its high level of plasma protein binding and low hepatic extraction ratio. The primary objective was to investigate changes in free drug concentration amongst patients with varying albumin concentrations.Methods: A HPLC-MS/MS method using C18 column (4.6 Â 150 mm, 5 μm) with ESI source in positive mode had been developed and validated for the quantitative determination of free pazaopanib concentration in human plasma. Prior to sample preparation, patient samples were subjected to 6-hour equilibrium dialysis with molecular weight cut-off set at 8000 Da. Results: The calibration curves were linear over the range of 5-1000 ng/mL, with a lower limit of quantification of 5 ng/mL. The intra-day and inter-day precisions and accuracies were all within AE 15 %, at 3 different quality controls. Higher median fraction unbound of pazopanib were observed in patients (n ¼ 17) with lower than normal albumin concentrations. Conclusion: With the developed assay, monitoring of plasma free concentrations may be evaluated as an indicator of pazopanib exposure in patients.

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Section: Effect Of Variable Albumin Levels In Human Plasma On Fu% Of Pazopanibmentioning

confidence: 98%

HPLC-MS/MS coupled with equilibrium dialysis method for quantification of free drug concentration of pazopanib in plasma

Toh

Pang

Shwe

et al. 2020

Heliyon

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Combination therapies for the treatment of HER2-positive breast cancer: current and future prospects

Brandão

Pondé

Poggio

et al. 2018

Expert Review of Anticancer Therapy

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HER2-positive disease is an aggressive subtype of breast cancer that has been revolutionized by anti-HER2 directed therapies. Multiple drugs have been developed and are currently in clinical use, including trastuzumab, lapatinib, pertuzumab, T-DM1, and neratinib, alone or combined in 'dual HER2-blockade' regimens. Areas covered: A comprehensive literature review was performed regarding the current state and the future of combination regimens containing anti-HER2 agents, focusing on their efficacy, toxicity, and cost-effectiveness. Expert commentary: The combination of trastuzumab/pertuzumab is approved in all disease settings, while trastuzumab/neratinib is approved in the adjuvant setting and trastuzumab/lapatinib in metastatic disease. Meanwhile, as breast cancer biology and resistance mechanisms become clearer, combinations with drugs like PI3K/Akt/mTOR inhibitors, CDK4/6 inhibitors, anti-PD(L)1 antibodies, endocrine therapy, and new anti-HER2 agents (panHER and HER2 tyrosine kinase inhibitors, bispecific antibodies, anti-HER3 antibodies, and antibody-drug conjugates) are being extensively tested in clinical trials. More specific strategies for the 'triple-positive' (estrogen receptor-positive/HER2-positive) disease are also being explored. However, there is an urgent need for the development of predictive biomarkers for a better tailoring of anti-HER2 directed therapy. This is the only way to further improve clinical outcomes and quality of life and to decrease costs and toxicities of unnecessary treatments.

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Does dose modification affect efficacy of first-line pazopanib in metastatic renal cell carcinoma?

Cited by 2 publications

References 7 publications

HPLC-MS/MS coupled with equilibrium dialysis method for quantification of free drug concentration of pazopanib in plasma

HPLC-MS/MS coupled with equilibrium dialysis method for quantification of free drug concentration of pazopanib in plasma

Combination therapies for the treatment of HER2-positive breast cancer: current and future prospects

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