+ Site Statistics
References:
54,258,434
Abstracts:
29,560,870
PMIDs:
28,072,757
+ Search Articles
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ PDF Full Text
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Translate
+ Recently Requested

Population pharmacokinetics of peritoneal, plasma ultrafiltrated and protein-bound oxaliplatin concentrations in patients with disseminated peritoneal cancer after intraperitoneal hyperthermic chemoperfusion of oxaliplatin following cytoreductive surgery: correlation between oxaliplatin exposure and thrombocytopenia



Population pharmacokinetics of peritoneal, plasma ultrafiltrated and protein-bound oxaliplatin concentrations in patients with disseminated peritoneal cancer after intraperitoneal hyperthermic chemoperfusion of oxaliplatin following cytoreductive surgery: correlation between oxaliplatin exposure and thrombocytopenia



Cancer ChemoTherapy and Pharmacology 74(3): 571-582



First, to evaluate the peritoneal (IP), plasma ultrafiltrated (UF) and protein-bound (B) pharmacokinetics (PK) of oxaliplatin after intraperitoneal hyperthermic chemoperfusion (HIPEC) following cytoreductive surgery. Second, to evaluate the relationship between oxaliplatin exposure and observed toxicity. IP, UF, and B concentrations from 75 patients treated by 30-min oxaliplatin-based HIPEC procedures were analysed according to a pharmacokinetic modelling approach using NONMEM. Oxaliplatin was administered in a 5 % dextrose solution (2 L/m(2)) at 360 (n = 58) or 460 mg/m(2) (n = 17). The most frequently observed toxicities were related to the peritoneal, systemic exposures and to the parameters corresponding to the oxaliplatin absorption from peritoneal cavity into plasma. IP (n = 536), UF (n = 669) and B (n = 661) concentrations were simultaneously described according to a five-compartment PK model with irreversible nonlinear binding from UF to B according to a Michaelis-Menten equation. The mean (±SD) maximum fraction of dose absorbed and elimination half-life from the peritoneum was 53.7 % (±8.5) and 0.49 h (±0.1), respectively. The mean (±SD) ratio AUC(IP)/AUC(UF) was 5.3 (±2) confirming the pharmacokinetic advantage of the procedure. Haemoperitoneum (22.7 %), neuropathy (18.7 %), grade 3/4 thrombocytopenia (13.3 %) were the most frequently reported toxicities. AUC(UF) accounts for approximately 12 % of the variation in the maximum percentage of platelet decrease (r = 0.35, p = 0.002). Thrombocytopenia was correlated with higher AUCUF, partly dependent on the extent and rate of oxaliplatin absorption. Despite a common dose administered, variability in peritoneal and systemic oxaliplatin exposures are observed, leading to differences in haematological toxicity between patients.

(PDF emailed within 0-6 h: $19.90)

Accession: 055054445

Download citation: RISBibTeXText

PMID: 25053386

DOI: 10.1007/s00280-014-2525-6


Related references

Population pharmacokinetics of hyperthermic intraperitoneal oxaliplatin in patients with peritoneal carcinomatosis after cytoreductive surgery. Cancer ChemoTherapy and Pharmacology 71(3): 693-704, 2013

Cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy with oxaliplatin for peritoneal carcinomatosis arising from colorectal cancer. Journal of Surgical Oncology 108(7): 438-443, 2014

Platelet Dynamics in Peritoneal Carcinomatosis Patients Treated with Cytoreductive Surgery and Hyperthermic Intraperitoneal Oxaliplatin. Aaps Journal 18(1): 239-250, 2016

Neutrophil dynamics in peritoneal carcinomatosis patients treated with cytoreductive surgery and hyperthermic intraperitoneal oxaliplatin. Clinical Pharmacokinetics 52(12): 1111-1125, 2014

Complete cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for peritoneal carcinomatosis from digestive tract cancer-New management with oxaliplatin plus irinotecan: A feasibility study in 37 patients. Journal of Clinical Oncology 26(15_suppl): 4084-4084, 2016

Safety and efficacy of hyperthermic intraperitoneal chemoperfusion with high-dose oxaliplatin in patients with peritoneal carcinomatosis. Annals of Surgical Oncology 15(2): 535-541, 2007

Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy with oxaliplatin for peritoneal mesothelioma: preliminary results and survival analysis. Surgical Oncology 24(1): 41-46, 2016

Prospective study of quality of life after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy using oxaliplatin for peritoneal carcinomatosis. Bulletin du Cancer 97(9): 1053-1060, 2010

Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for colorectal peritoneal carcinomatosis: higher complication rate for oxaliplatin compared to Mitomycin C. Acta Chirurgica Belgica 106(3): 302-306, 2006

Safety of intraperitoneal Mitomycin C versus intraperitoneal oxaliplatin in patients with peritoneal carcinomatosis of colorectal cancer undergoing cytoreductive surgery and HIPEC. European Journal of Surgical Oncology 44(2): 220-227, 2017

The treatment of peritoneal carcinomatosis of colorectal cancer with complete cytoreductive surgery and hyperthermic intraperitoneal peroperative chemotherapy (HIPEC) with oxaliplatin: a Belgian multicentre prospective phase II clinical study. Annals of Surgical Oncology 19(7): 2186-2194, 2012

A phase I trial of oxaliplatin for intraperitoneal hyperthermic chemoperfusion for the treatment of peritoneal surface dissemination from colorectal and appendiceal cancers. Annals of Surgical Oncology 15(8): 2137-2145, 2008

Rationale for heating oxaliplatin for the intraperitoneal treatment of peritoneal carcinomatosis: a study of the effect of heat on intraperitoneal oxaliplatin using a murine model. Annals of Surgery 254(1): 138-144, 2011

Complete cytoreductive surgery plus intraperitoneal chemohyperthermia with oxaliplatin for peritoneal carcinomatosis of colorectal origin. Journal of Clinical Oncology 27(5): 681-685, 2009

Peritoneal carcinomatosis of colorectal origin: Long-term results of intraperitoneal chemohyperthermia with oxaliplatin following complete cytoreductive surgery. Gastroentérologie Clinique et Biologique 30(10-Part-P1): 1200-1204, 2006