title: Pharmacokinetics of concomitant cisplatin and paclitaxel administered by hyperthermic intraperitoneal chemotherapy to patients with peritoneal carcinomatosis from epithelial ovarian cancer.
abstract: BACKGROUND
  Hyperthermic intraperitoneal chemotherapy (HIPEC) is advised as a treatment option for epithelial ovarian cancer (EOC) with peritoneal carcinomatosis. This study was designed to define the pharmacokinetics of cisplatin (CDDP) and paclitaxel (PTX) administered together during HIPEC.
  
  
  METHODS
  Thirteen women with EOC underwent cytoreductive surgery (CRS) and HIPEC, with CDDP and PTX. Blood, peritoneal perfusate and tissue samples were harvested to determine drug exposure by high-performance liquid chromatography and matrix-assisted laser desorption ionization imaging mass spectrometry (IMS).
  
  
  RESULTS
  The mean maximum concentrations of CDDP and PTX in perfusate were, respectively, 24.8±10.4 μg ml(-1) and 69.8±14.3 μg ml(-1); in plasma were 1.87±0.4 μg ml(-1) and 0.055±0.009 μg ml(-1). The mean concentrations of CDDP and PTX in peritoneum at the end of HIPEC were 23.3±8.0 μg g(-1) and 30.1±18.3 μg(-1)g(-1), respectively. The penetration of PTX into the peritoneal wall, determined by IMS, was about 0.5 mm. Grade 3-4 surgical complications were recorded in four patients, five patients presented grade 3 and two patients presented grade 4 hematological complications.
  
  
  CONCLUSIONS
  HIPEC with CDDP and PTX after CRS is feasible with acceptable morbidity and has a favorable pharmacokinetic profile: high drug concentrations are achieved in peritoneal tissue with low systemic exposure. Larger studies are needed to demonstrate its efficacy in patients with microscopic postsurgical residual tumours in the peritoneal cavity.
authors.affiliation: General Surgery Unit, Papa Giovanni XXIII Hospital, Piazza OMS 1, 24127 Bergamo, Italy.
authors.forename: L
authors.initials: L
authors.lastname: Ansaloni
authors.affiliation: General Surgery Unit, Papa Giovanni XXIII Hospital, Piazza OMS 1, 24127 Bergamo, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Coccolini
authors.affiliation: Department of Oncology, IRCCS-Istituto di Ricerche Farmacologiche Mario Negri, Via La Masa 19, 20156 Milano, Italy.
authors.forename: L
authors.initials: L
authors.lastname: Morosi
authors.affiliation: 1] Department of Oncology, IRCCS-Istituto di Ricerche Farmacologiche Mario Negri, Via La Masa 19, 20156 Milano, Italy [2] Department of Medical Biotechnologies and Translational Medicine, University of Milan, Via Vanvitelli 32, 20156 Milano, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Ballerini
authors.affiliation: General Surgery Unit, Papa Giovanni XXIII Hospital, Piazza OMS 1, 24127 Bergamo, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Ceresoli
authors.affiliation: Gynecology and Obstetrics Unit, Papa Giovanni XXIII Hospital, Piazza OMS 1, 24127 Bergamo, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Grosso
authors.affiliation: General Surgery Unit, Papa Giovanni XXIII Hospital, Piazza OMS 1, 24127 Bergamo, Italy.
authors.forename: P
authors.initials: P
authors.lastname: Bertoli
authors.affiliation: Gynecology and Obstetrics Unit, Papa Giovanni XXIII Hospital, Piazza OMS 1, 24127 Bergamo, Italy.
authors.forename: L M
authors.initials: LM
authors.lastname: Busci
authors.affiliation: General Surgery Unit, Papa Giovanni XXIII Hospital, Piazza OMS 1, 24127 Bergamo, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Lotti
authors.affiliation: IRCCS-Istituto di Ricerche Farmacologiche Mario Negri, Department of Environmental Health, Via La Masa 19, 20156 Milano, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Cambria
authors.affiliation: General Surgery Unit, Papa Giovanni XXIII Hospital, Piazza OMS 1, 24127 Bergamo, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Pisano
authors.affiliation: Gynecology and Obstetrics Unit, Papa Giovanni XXIII Hospital, Piazza OMS 1, 24127 Bergamo, Italy.
authors.forename: D
authors.initials: D
authors.lastname: Rossetti
authors.affiliation: Gynecology and Obstetrics Unit, Papa Giovanni XXIII Hospital, Piazza OMS 1, 24127 Bergamo, Italy.
authors.forename: L
authors.initials: L
authors.lastname: Frigerio
authors.affiliation: Department of Oncology, IRCCS-Istituto di Ricerche Farmacologiche Mario Negri, Via La Masa 19, 20156 Milano, Italy.
authors.forename: M
authors.initials: M
authors.lastname: D'Incalci
authors.affiliation: Department of Oncology, IRCCS-Istituto di Ricerche Farmacologiche Mario Negri, Via La Masa 19, 20156 Milano, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Zucchetti
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000493:pharmacokinetics*; D019540:Area Under Curve; D002277:Carcinoma / Q000188:drug therapy* / Q000556:secondary; D002945:Cisplatin / Q000008:administration & dosage; D005260:Female; D006801:Humans; D006979:Hyperthermia, Induced; D007263:Infusions, Parenteral; D008297:Male; D008875:Middle Aged; D009375:Neoplasms, Glandular and Epithelial / Q000188:drug therapy* / Q000556:secondary; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000473:pathology; D017239:Paclitaxel / Q000008:administration & dosage; D010534:Peritoneal Neoplasms / Q000188:drug therapy* / Q000556:secondary; D010537:Peritoneum / Q000378:metabolism
chemical_list: D017239:Paclitaxel; D002945:Cisplatin