title: Platelet Dynamics in Peritoneal Carcinomatosis Patients Treated with Cytoreductive Surgery and Hyperthermic Intraperitoneal Oxaliplatin.
abstract: The aim of the study was to characterize the platelet count (PLT) dynamics in peritoneal carcinomatosis patients treated with cytoreductive surgery (CRS) and hyperthermic intraperitoneal oxaliplatin (HIO). Data from patients treated with CRS alone (N = 18) or CRS and HIO (N = 62) were used to estimate the baseline platelet count (PLT0), rate constants for platelet maturation (k tr ) and platelet random destruction (k s ), feedback on progenitor cell proliferation (γ), and the drug-specific model parameters (α, β). Plasma oxaliplatin concentrations, C p , reduced the proliferation rate of progenitor cells (k prol) according to a power function α × C p (β) . The surgery effect on k prol and k s was explored. The typical values (between subject variability) of the PLT0, k tr , k s , γ, α, and β were estimated to be 237 × 10(9) cells/L (32.9%), 7.09 × 10(-3) h(-1) (47.1%), 8.86 × 10(-3) h(-1) (80.0%), 0.621, 0.88 L/mg (56.9%), and 2.63. Surgery induced a maximal 2.09-fold increase in k prol that was attenuated with a half-life of 8.42 days. Splenectomy decreased k s by 47.5%. Age, sex, body surface area, sex, total proteins, and HIO carrier solution did not impact the model parameters. The model developed suggests that, following CRS and HIO, thrombocytopenia and thrombocytosis were reversible and short-lasting; the severity of the thrombocytopenia and thrombocytosis was inversely correlated, with splenectomized patients having thrombocytopenia of lower severity and thrombocytosis of higher severity; and the HIO dose and treatment duration determine the severity and duration of the thrombocytopenia. Higher HIO dose or longer treatment duration could be used without substantially increasing the risk of major hematological toxicity.
authors.affiliation: Pharmacy and Pharmaceutical Technology Department, University of Valencia, Valencia, Spain.
authors.forename: Carlos
authors.initials: C
authors.lastname: Pérez-Ruixo
authors.affiliation: Platform of Oncology, Hospital Quirón Torrevieja, Partida de la Loma s/n, 03184, Torrevieja, Alicante, Spain. belen.valenzuela@quiron.es.|Cathedra of Multidisciplinary Oncology, UCAM Catholic University of San Antonio, Murcia, Spain. belen.valenzuela@quiron.es.
authors.forename: Belén
authors.initials: B
authors.lastname: Valenzuela
authors.affiliation: Pharmacy and Pharmaceutical Technology Department, University of Valencia, Valencia, Spain.
authors.forename: José Esteban
authors.initials: JE
authors.lastname: Peris
authors.affiliation: Platform of Oncology, Hospital Quirón Torrevieja, Partida de la Loma s/n, 03184, Torrevieja, Alicante, Spain.|Cathedra of Multidisciplinary Oncology, UCAM Catholic University of San Antonio, Murcia, Spain.
authors.forename: Pedro
authors.initials: P
authors.lastname: Bretcha-Boix
authors.affiliation: Pharmacy and Clinical Nutrition Group, University CEU Cardenal Herrera, Elche, Alicante, Spain.
authors.forename: Vanesa
authors.initials: V
authors.lastname: Escudero-Ortiz
authors.affiliation: Platform of Oncology, Hospital Quirón Torrevieja, Partida de la Loma s/n, 03184, Torrevieja, Alicante, Spain.|Cathedra of Multidisciplinary Oncology, UCAM Catholic University of San Antonio, Murcia, Spain.
authors.forename: José
authors.initials: J
authors.lastname: Farré-Alegre
authors.affiliation: Clinical Pharmacology & Pharmacometrics, Janssen Research & Development, Beerse, Belgium.
authors.forename: Juan José
authors.initials: JJ
authors.lastname: Pérez-Ruixo
mesh_terms: D000328:Adult; D000368:Aged; D000375:Aging / Q000378:metabolism; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D001792:Blood Platelets / Q000187:drug effects*; D002277:Carcinoma / Q000097:blood* / Q000601:surgery / Q000628:therapy*; D049109:Cell Proliferation; D003131:Combined Modality Therapy; D065426:Cytoreduction Surgical Procedures; D005260:Female; D006207:Half-Life; D006801:Humans; D006979:Hyperthermia, Induced; D007274:Injections, Intraperitoneal; D008297:Male; D008875:Middle Aged; D009944:Organoplatinum Compounds / Q000008:administration & dosage / Q000627:therapeutic use*; D000077150:Oxaliplatin; D010534:Peritoneal Neoplasms / Q000097:blood* / Q000601:surgery / Q000628:therapy*; D013156:Splenectomy; D013234:Stem Cells / Q000187:drug effects; D013921:Thrombocytopenia / Q000097:blood / Q000139:chemically induced; D013922:Thrombocytosis / Q000097:blood / Q000139:chemically induced
chemical_list: D000970:Antineoplastic Agents; D009944:Organoplatinum Compounds; D000077150:Oxaliplatin
keywords: cytoreductive surgery; hyperthermic intraperitoneal chemotherapy (HIPEC); oxaliplatin; peritoneal carcinomatosis; population pharmacokinetic pharmacodynamic modeling; thrombocytopenia; thrombocytosis