Pharmacokinetics of concomitant cisplatin and paclitaxel administered by hyperthermic intraperitoneal chemotherapy to patients with peritoneal carcinomatosis from epithelial ovarian cancer

• Published in: British journal of cancer Vol. 112; no. 2; pp. 306 - 312
• Main Authors: Ansaloni, L, Coccolini, F, Morosi, L, Ballerini, A, Ceresoli, M, Grosso, G, Bertoli, P, Busci, L M, Lotti, M, Cambria, F, Pisano, M, Rossetti, D, Frigerio, L, D'Incalci, M, Zucchetti, M
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 20.01.2015; Nature Publishing Group
• Subjects: 631/154/436/1729; 692/699/67/1059/99; 692/699/67/1517/1709; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols - administration & dosage; Antineoplastic Combined Chemotherapy Protocols - pharmacokinetics; Area Under Curve; Biomedical and Life Sciences; Biomedicine; Cancer Research; Carcinoma - drug therapy; Carcinoma - secondary; Cisplatin - administration & dosage; Clinical Study; Drug Resistance; Epidemiology; Female; Humans; Hyperthermia, Induced; Infusions, Parenteral; Male; Middle Aged; Molecular Medicine; Neoplasms, Glandular and Epithelial - drug therapy; Neoplasms, Glandular and Epithelial - secondary; Oncology; Ovarian cancer; Ovarian Neoplasms - drug therapy; Ovarian Neoplasms - pathology; Paclitaxel - administration & dosage; Peritoneal Neoplasms - drug therapy; Peritoneal Neoplasms - secondary; Peritoneum - metabolism; pharmacokinetics; HIPEC; peritoneal carcinomatosis; intraperitoneal chemotherapy; MALDI imaging
• ISSN: 0007-0920; 1532-1827
• DOI: 10.1038/bjc.2014.602

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  μ g ml −1 and 69.8±14.3  μ g ml −1 ; in plasma were 1.87±0.4  μ g ml −1 and 0.055±0.009  μ g ml −1 . The mean concentrations of CDDP and PTX in peritoneum at the end of HIPEC were 23.3±8.0  μ g g −1 and 30.1±18.3  μ g −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.