title: Pharmacokinetic study of docetaxel in intraoperative hyperthermic i.p. chemotherapy for ovarian cancer.
abstract: The purpose of this study was to evaluate the pharmacokinetics and toxicity of docetaxel in continuous hyperthermic perfusion peritoneal chemotherapy (CHPPC) after cytoreductive surgery for peritoneal involvement of gynecological malignancies, mainly ovarian cancer. Eighteen patients, with a mean age of 64 years (range 51-80), underwent cytoreductive surgery and subsequent CHPPC with 75 mg/m2 docetaxel at 41-43 degrees C. One patient was treated twice. In eight cases, peritoneal fluid and blood samples were obtained for pharmacokinetic analysis. Death occurred in two heavily pretreated elderly patients with a high volume i.p. tumor recurrence, probably reflecting poor patient selection (mortality rate 10.5%). Other complications, mainly minor, were recorded after 63% of the procedures. Hematological docetaxel-induced toxicity was limited, while the incidence of wound complications was relatively high and probably caused by the direct exposure of the wound to docetaxel during CHPPC. The maximal i.p. versus plasma concentration ratio ranged from 17 to 95 (average 45), while the i.p. versus systemic exposure ratio varied between 105 and 555 (average 207). We conclude that the use of docetaxel in CHPPC following cytoreductive surgery seems feasible and results in a high i.p. versus systemic exposure ratio. The AUC for the peritoneal cavity is on average 13-27 times higher after i.p. administration of 75 mg/m2 during CHPPC than the AUC achieved in the systemic compartment after i.v. administration of the recommended dose of 100 mg/m2, while docetaxel-induced systemic toxicity is highly limited.
authors.affiliation: Department of Surgical Oncology, University Hospital, Herakleion, Greece. debree@edu.uoc.gr
authors.forename: Eelco
authors.initials: E
authors.lastname: de Bree
authors.forename: Hilde
authors.initials: H
authors.lastname: Rosing
authors.forename: Jos H
authors.initials: JH
authors.lastname: Beijnen
authors.forename: John
authors.initials: J
authors.lastname: Romanos
authors.forename: John
authors.initials: J
authors.lastname: Michalakis
authors.forename: Vasilis
authors.initials: V
authors.lastname: Georgoulias
authors.forename: Dimitris D
authors.initials: DD
authors.lastname: Tsiftsis
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000493:pharmacokinetics*; D019540:Area Under Curve; D001682:Biological Availability; D002277:Carcinoma / Q000378:metabolism* / Q000556:secondary / Q000601:surgery; D003131:Combined Modality Therapy; D000077143:Docetaxel; D005260:Female; D006801:Humans; D006979:Hyperthermia, Induced; D007274:Injections, Intraperitoneal; D007430:Intraoperative Care; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D017239:Paclitaxel / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics*; D010534:Peritoneal Neoplasms / Q000378:metabolism* / Q000556:secondary / Q000601:surgery; D043823:Taxoids; D014018:Tissue Distribution
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D043823:Taxoids; D000077143:Docetaxel; D017239:Paclitaxel