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Title
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Dose regimen rationale for panitumumab in cancer patients : to be based on body weight or not
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Author
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Abstract
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| Introduction: Body weight can affect exposure, safety and efficacy of antibody-based therapies; sometimes these effects may not be clinically relevant. Panitumumab is approved for wild-type RAS metastatic colorectal cancer, using a body weight-based dosing regimen. Recently, a report cited fixed-dose usage of panitumumab, rather than approved body weight-based dosing. The current work evaluates optimal dosing regimen scientifically based on clinical data, modeling and simulation. Herein, we assessed the effect of fixed and body weight-based dosing on panitumumab pharmacokinetics to determine which approach resulted in the least interpatient pharmacokinetic variability. Patients and Methods: From the Vectibix program, 352 patients enrolled in three studies were evaluated; they had received panitumumab (body weight-based dose: 6 mg/kg every 2 weeks) and had pharmacokinetic (maximum serum [C-max] and trough [C-min] concentrations) and body weight data available. Additionally, concentration-time profiles at fixed (480 mg) and body weight-based doses (6 mg/kg) were simulated using a population pharmacokinetics model developed from 1200 patients. Results: After administration of panitumumab 6 mg/kg, C-max and C-min increased with increasing body weight; the mean C-max and C-min for patients weighing <65 kg (lower quartile) were 23% and 30% lower, respectively, than for those weighing >88 kg (upper quartile). The simulated area under the concentration-time curve (AUC) data also indicated that overall panitumumab exposure increased with increasing body weight for the body weight-based regimen. When AUC was simulated for a fixed dose (480 mg), the opposite effect was observed. Over the range of body weights, interpatient variability in simulated AUC was lower for the weight-based dose (29%) than for the fixed dose (34%). Conclusion: Results demonstrate that the weight-based dose (6 mg/kg) reduced variability in panitumumab exposure across the range of body weights compared with the fixed-dose approach, indicating that a body weight-based approach is the recommended patient dosing strategy. |
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Language
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English
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Source (journal)
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Clinical pharmacology : advances and applications. - Place of publication unknown
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Publication
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Place of publication unknown
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publisher unknown
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2020
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ISSN
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1179-1438
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DOI
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10.2147/CPAA.S262949
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Volume/pages
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12
(2020)
, p. 109-114
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ISI
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000555465300001
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Pubmed ID
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32801947
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Full text (Publisher's DOI)
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Full text (open access)
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