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24.08.2023 | Short Communication

Pazopanib pharmacokinetically guided dose optimization in three cancer patients with gastrointestinal resection

verfasst von: Cléa Tardy, Alicja Puszkiel, Pascaline Boudou-Rouquette, Sixtine De Percin, Jérôme Alexandre, Marion Berge, Guillaume Ulmann, Benoit Blanchet, Rui Batista, Francois Goldwasser, Audrey Thomas Schoemann

Erschienen in: Cancer Chemotherapy and Pharmacology | Ausgabe 2/2024

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Abstract

Purpose

Pazopanib is approved in advanced renal cell carcinoma (RCC) and soft-tissue sarcoma at a flat-fixed dose despite a large pharmacokinetics interindividual variability and a narrow therapeutic index. To our knowledge, pazopanib exposure in patients with gastrointestinal resections (GIR) has not been described. This report focuses on feasibility of pharmacokinetics-guided dose escalation in these patients and clinical implications for their management.

Method

A retrospective data collection was performed for three patients with GIR treated with pazopanib, including pazopanib plasma concentrations (high-performance liquid chromatography with UV detection) and treatment adherence (Girerd score).

Case presentation

First patient (55-year-old man, RCC, gastric bypass surgery) pazopanib C_min,ss at day 39 was 4.1 mg/L. Dose escalation to 1800 mg/day fractionated allowed to reach C_min,ss of 18.5 mg/L (target threshold in RCC patients: 20.5 mg/L). Patient 2 (50-year-old woman, metastatic myxofibrosarcoma, gastric band) showed C_min,ss of 4.0 mg/L at day 13. In patient 3 (49-year-old man, gastric malignant peripheral nerve sheath tumor, gastrectomy), C_min,ss at day 13 was 2.7 mg/L. For these two patients, intake with food and dose fractioning only slightly increased pazopanib C_min,ss to 12.0 mg/L and 6.5 mg/L, respectively (therapeutic threshold in sarcoma patients: 27 mg/L). Treatment adherence was good in all patients.

Conclusion

Optimal pazopanib exposure cannot be achieved in patients with GIR, and thus, other therapeutic strategies should be encouraged. Pretherapeutic assessment seems crucial to evaluate factors as bariatric surgery that may impact pazopanib concentrations. Therapeutic drug monitoring could be helpful to optimize pazopanib response in these patients.

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Titel: Pazopanib pharmacokinetically guided dose optimization in three cancer patients with gastrointestinal resection
verfasst von: Cléa Tardy
Alicja Puszkiel
Pascaline Boudou-Rouquette
Sixtine De Percin
Jérôme Alexandre
Marion Berge
Guillaume Ulmann
Benoit Blanchet
Rui Batista
Francois Goldwasser
Audrey Thomas Schoemann
Publikationsdatum: 24.08.2023
Verlag: Springer Berlin Heidelberg
Erschienen in: Cancer Chemotherapy and Pharmacology / Ausgabe 2/2024
Print ISSN: 0344-5704
Elektronische ISSN: 1432-0843
DOI: https://doi.org/10.1007/s00280-023-04574-z

Springer Medizin

Pazopanib pharmacokinetically guided dose optimization in three cancer patients with gastrointestinal resection