Intraperitoneal clearance as a potential biomarker of cisplatin after intraperitoneal perioperative chemotherapy: a population pharmacokinetic study.
Bernard Royer
(1, 2, 3, 4)
,
Elsa Kalbacher
(5)
,
Sylvain Onteniente
(4)
,
Vincent Jullien
(6, 7)
,
Damien Montange
(3, 4)
,
Sarah Piedoux
(4)
,
Antoine Thiery-Vuillemin
(5)
,
Delphine Delroeux
(8)
,
Sébastien Pili-Floury
(9)
,
Emmanuel Guardiola
(5)
,
Marielle Combe
(9, 10)
,
Patrice Muret
(1, 2, 3, 4)
,
Virginie Nerich
(11)
,
Bruno Heyd
(8)
,
Bruno Chauffert
(12)
,
Jean-Pierre Kantelip
(4)
,
Xavier Pivot
(1, 2, 3, 5)
1
Inserm CIC 1431 -
Centre d'Investigation Clinique de Besançon
2 UFC - Université de Franche-Comté
3 RIGHT - Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC (UMR INSERM 1098)
4 Laboratoire de Pharmacologie Clinique et Toxicologie [CHRU Besancon]
5 Service d'Oncologie Médicale [CHRU Besançon]
6 Service de pharmacologie
7 U1129 - Epilepsies de l'Enfant et Plasticité Cérébrale
8 Service d'oncologie chirurgicale
9 Service d'anesthésie et soins intensifs [CHRU Besançon]
10 CHRU Besançon - Centre Hospitalier Régional Universitaire de Besançon
11 Pôle pharmaceutique [CHRU Besançon]
12 Service d'oncologie
2 UFC - Université de Franche-Comté
3 RIGHT - Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC (UMR INSERM 1098)
4 Laboratoire de Pharmacologie Clinique et Toxicologie [CHRU Besancon]
5 Service d'Oncologie Médicale [CHRU Besançon]
6 Service de pharmacologie
7 U1129 - Epilepsies de l'Enfant et Plasticité Cérébrale
8 Service d'oncologie chirurgicale
9 Service d'anesthésie et soins intensifs [CHRU Besançon]
10 CHRU Besançon - Centre Hospitalier Régional Universitaire de Besançon
11 Pôle pharmaceutique [CHRU Besançon]
12 Service d'oncologie
Bernard Royer
Connectez-vous pour contacter l'auteur
- Function : Correspondent author
- PersonId : 937992
Connectez-vous pour contacter l'auteur
Virginie Nerich
- Function : Author
- PersonId : 762382
- ORCID : 0000-0002-0351-6040
Bruno Chauffert
- Function : Author
- PersonId : 919116
- ORCID : 0000-0001-7533-5401
- IdRef : 067133428
Abstract
BACKGROUND: Intraperitoneal (IP) perioperative chemotherapy with cisplatin is an interesting option in ovarian cancer treatment. A combination of cisplatin with IP epinephrine (already shown to improve IP and decrease systemic platinum (Pt) exposure) was evaluated using a population pharmacokinetic analysis. METHODS: Data from 55 patients treated with cisplatin-based IP perioperative chemotherapy with (n=26) or without (n=29) epinephrine were analysed using NONMEM. RESULTS: Epinephrine halves clearance between peritoneum and serum (IPCL) and increases the Pt central volume of distribution, IP exposure and penetration in tissue. IPCL has a better predictive value than any other parameter with respect to renal toxicity. CONCLUSION: This confirms that IPCL could be useful in assessing renal toxicity. As IPCL is also linked to tissue penetration and IP exposure, it may be proposed as biomarker. In addition to a Bayesian estimation, we propose a single-sample calculation-way to assess it. Prospective studies are needed to validate IPCL as a biomarker in this context.