Systemic exposure of oxaliplatin and docetaxel in gastric cancer patients with peritonitis carcinomatosis treated with intraperitoneal hyperthermic chemotherapy |
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| Affiliation: | 1. Department of Surgical Oncology, the Netherlands Cancer Institute/Antoni van Leeuwenhoek Hospital, Plesmanlaan 121, 1066 CX, Amsterdam, the Netherlands;2. Departments of Surgery, Sint Antonius Hospital, Koekoekslaan 1, 3435 CM, Nieuwegein, the Netherlands;3. Department of Gastrointestinal Oncology, the Netherlands Cancer Institute/Antoni van Leeuwenhoek Hospital, Plesmanlaan 121, 1066 CX, Amsterdam, the Netherlands;4. Department of Medical Oncology, Sint Antonius Hospital, Koekoekslaan 1, 3435 CM, Nieuwegein, the Netherlands;5. Clinical Perfusion, Heartbeat. Kerkstraat 3a, 3755 CK, Eemnes, the Netherlands;6. Department of Clinical Pharmacology, the Netherlands Cancer Institute/Antoni van Leeuwenhoek Hospital, Plesmanlaan 121, 1066 CX, Amsterdam, the Netherlands;7. Department of Pharmacy, the Netherlands Cancer Institute/Antoni van Leeuwenhoek Hospital, Plesmanlaan 121, 1066 CX, Amsterdam, the Netherlands;8. Department of Clinical Pharmacy, University Medical Center Utrecht. Heidelberglaan 100, 3584 CX, Utrecht, the Netherlands;1. Department of Surgery, Mater Misericordiae University Hospital, Dublin 7, Ireland;2. UCD Centre for Precision Surgery, Section of Surgery and Surgical Specialties, School of Medicine, University College Dublin, Dublin, Ireland;1. Breast Center, San Giovanni-Addolorata Hospital, Rome, Italy;2. Breast Unit Humanitas Cancer Centre, Catania, Italy;3. Breast Unit - ASUGI DSMCS, Trieste University, Italy;4. Department of Pathology-Breast Unit ASL TO 5, Moncalieri (TO), Italy;5. Breast Unit Policlinico di Sant’Orsola, Bologna University, Italy;6. Breast Unit Humanitas Cancer Centre, Rozzano, Italy;7. Senonetwork Italia Onlus, Florence, Italy;8. Breast Unit Perrino Hospital, Brindisi, Italy;1. Division of Surgery and Perioperative Medicine, Flinders Medical Centre, Bedford Park, Adelaide, South Australia, Australia;2. College of Medicine and Public Health, Flinders University, South Australia, Australia;3. Department of Visceral, Vascular and Endocrine Surgery, Martin Luther University Halle-Wittenberg, Halle (Saale), Saxony-Anhalt, Germany;1. Department of Urology, University Hospital Frankfurt, Frankfurt am Main, Germany;2. Cancer Prognostics and Health Outcomes Unit, Division of Urology, University of Montréal Health Center, Montréal, Québec, Canada;3. Martini-Klinik Prostate Cancer Center, University Hospital Hamburg-Eppendorf, Hamburg, Germany;4. Department of Urology and Division of Experimental Oncology, URI, Urological Research Institute, IRCCS San Raffaele Scientific Institute, Milan, Italy;5. European Institute of Oncology, Milan, Italy;6. Department of Urology, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria;7. Institute for Urology and Reproductive Health, I.M. Sechenov First Moscow State Medical University, Moscow, Russia;8. Department of Urology, University of Jordan, Amman, Jordan;9. Department of Urology, McGill University Health Centre, Montréal, Québec, Canada;10. Department of Urologic Sciences, Vancouver Prostate Centre, University of British Columbia, Vancouver, British Colombia, Canada |
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| Abstract: | In the PERISCOPE I study, gastric cancer patients with limited peritoneal dissemination were treated with systemic chemotherapy followed by (sub)total gastrectomy, cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC) with 460 mg/m2 hyperthermic oxaliplatin followed by normothermic docetaxel in escalating doses (0, 50, 75 mg/m2). In total, 25 patients completed the study protocol. Plasma samples were collected before the start of the HIPEC procedure, after oxaliplatin washing, after docetaxel washing and the following morning. Median peak plasma concentrations were 5.5110−3 mg/ml for oxaliplatin, 89110−6 mg/ml for docetaxel (dose 50 mg/m2) and 113110−6 mg/ml for docetacel (dose 75 mg/m2). The following morning median plasma concentrations were 32% and 4% of the measured peak concentrations for oxaliplatin and docetaxel, respectively. For both cytostatic agents, no correlation was found between intraperitoneal fluid concentration and peak plasma concentration. High doses oxaliplatin and docetaxel can be given intraperitoneally without causing potentially toxic systemic concentrations. |
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| Keywords: | Gastric cancer Hyperthermic intraperitoneal chemotherapy Oxaliplatin Docetaxel Plasma concentration Perfusion |
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