Cancer Chemotherapy and Pharmacology. 2008 Jul 25. [Epub ahead of print] [Link]
Van der Speeten K, Stuart OA, Mahteme H, Sugarbaker PH.
Department of Surgical Oncology, Ziekenhuis Oost-Limburg, Schiepse Bos 6, 3600, Genk, Belgium, firstname.lastname@example.org.
Purpose: A pharmacologic analysis of intracavitary doxorubicin in the treatment of patients with intracavitary cancer dissemination was performed to further evaluate the possible benefits of this treatment modality.
Methods: Twenty appendiceal malignancy patients with peritoneal carcinomatosis (PC), three appendiceal malignancy patients with direct extension into the pleural cavity, 20 patients with peritoneal mesothelioma and one patient with pleural mesothelioma were available for pharmacologic monitoring. After intraperitoneal or intrapleural administration of doxorubicin, plasma and peritoneal fluid samples were obtained at 15, 30, 45, 60 and 90 min in all patients. After intrapleural administration, plasma and pleural fluid samples were collected at similar intervals. Tumor and normal tissues were obtained when available. Doxorubicin concentrations were determined by high-performance liquid chromatography (HPLC).
Results: Intraperitoneal doxorubicin showed a prolonged retention in the peritoneal cavity. Doxorubicin concentrations in tumor tissue were consistently elevated above intraperitoneal concentrations from 30 through 90 min. For appendiceal malignancy, the concentrations of doxorubicin were significantly higher in minimally aggressive mucinous tumors. Pleural chemotherapy solutions retained doxorubicin to a greater extent than peritoneal fluid.
Conclusions: Doxorubicin shows characteristics favorable for intracavitary administration with sequestration of doxorubicin in cancer nodules.
Keywords: Intraperitoneal chemotherapy – Intrapleural chemotherapy – Doxorubicin – Pharmacokinetics – Pharmacodynamics – Appendiceal cancer – Peritoneal mesothelioma – Pleural mesothelioma