Luigi Frigerio

304 - Br j cancer. 2014 dec 2. doi: 10.1038/bjc.2014.602. [epub ahead of print]
pharmacokinetics of concomitant cisplatin and paclitaxel administered by hyperthermic intraperitoneal chemotherapy to patients with peritoneal carcinomatosis from epithelial ovarian cancer.
Ansaloni L1, Coccolini F1, Morosi L2, Ballerini A3, Ceresoli M1, Grosso G4, Bertoli P1, Busci LM4, Lotti M1, Cambria F5, Pisano M1, Rossetti D4, Frigerio L4, D’Incalci M2, Zucchetti M2.
Author information1General Surgery Unit, Papa Giovanni XXIII Hospital, Piazza OMS 1, 24127 Bergamo, Italy.2Department of Oncology, IRCCS-Istituto di Ricerche Farmacologiche Mario Negri, Via La Masa 19, 20156 Milano, Italy.31] 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.4Gynecology and Obstetrics Unit, Papa Giovanni XXIII Hospital, Piazza OMS 1, 24127 Bergamo, Italy.5IRCCS-Istituto di Ricerche Farmacologiche Mario Negri, Department of Environmental Health, Via La Masa 19, 20156 Milano, Italy.
Abstract
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-1g-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.British Journal of Cancer (2014) advance online publication, 2 December 2014; doi:10.1038/bjc.2014.602