Intraperitoneal clearance as a potential biomarker of cisplatin after intraperitoneal perioperative chemotherapy: a population pharmacokinetic study

被引：9

作者：

Royer, B. ^{[1
,2
,3
,4
]}

Kalbacher, E. ^{[5
]}

Onteniente, S. ^{[1
]}

Jullien, V. ^{[6
]}

Montange, D. ^{[1
,2
]}

Piedoux, S. ^{[1
]}

Thiery-Vuillemin, A. ^{[5
]}

Delroeux, D. ^{[7
]}

Pili-Floury, S. ^{[8
]}

Guardiola, E. ^{[5
]}

Combe, M. ^{[8
]}

Muret, P. ^{[1
,2
,3
,4
]}

Nerich, V. ^{[9
]}

Heyd, B. ^{[7
]}

Chauffert, B. ^{[10
]}

Kantelip, J-P ^{[1
]}

Pivot, X. ^{[2
,3
,4
,5
]}

机构：

[1] CHU Jean Minjoz, Lab Pharmacol Clin, Dept Pharmacol, CHU Besancon, F-25030 Besancon, France

[2] INSERM, UMR645, Besancon, France

[3] CHU Besancon, Clin Invest Ctr CIC, BT 506, F-25030 Besancon, France

[4] Univ Franche Comte, IFR133, F-25030 Besancon, France

[5] CHU Besancon, Dept Oncol, F-25030 Besancon, France

[6] Paris Descartes Univ, Cochin St Vincent de Paul Hosp, INSERM, Dept Pharmacol,U663, Paris, France

[7] CHU Besancon, Dept Surg Oncol, F-25030 Besancon, France

[8] CHU Besancon, Dept Anesthesiol & Intens Care Med, F-25030 Besancon, France

[9] CHU Besancon, Dept Pharm, F-25030 Besancon, France

[10] CHU Amiens, Dept Oncol, Amiens, France

来源：

BRITISH JOURNAL OF CANCER | 2012年 / 106卷 / 03期

关键词：

biomarker; cisplatin; epinephrine; intraperitoneal perioperative chemotherapy; population pharmacokinetics; OVARIAN-CANCER PATIENTS; PERITONEAL CARCINOMATOSIS; INTRAOPERATIVE CHEMOTHERAPY; EPINEPHRINE; PENETRATION; MODEL; HYPERTHERMIA; TUMORS; SERUM; STAGE;

D O I：

10.1038/bjc.2011.557

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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. British Journal of Cancer (2012) 106, 460-467. doi: 10.1038/bjc.2011.557 www.bjcancer.com Published online 15 December 2011 (C) 2012 Cancer Research UK

引用

页码：460 / 467

页数：8

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