Pharmacokinetic Study of Perioperative Intravenous Ifosfamide
2011 (English)In: Annals of Surgical Oncology, ISSN 1068-9265, E-ISSN 1534-4681, 185092- p.Article in journal (Refereed) Published
The use of cancer chemotherapy as part of a surgical procedure in the management of patients with peritoneal carcinomatosis has gained prominence in recent years with selected patients showing benefit. Various combinations of intraperitoneal and systemic chemotherapy used with moderate hyperthermia constitute the cytotoxic component of this therapy. Ifosfamide, being a heat synergized drug, may be an important chemotherapy agent to use when attempting to optimize this treatment strategy.
Materials and methods
16 Patients with peritoneal surface malignancy following cancer resection were treated with intraperitoneal hyperthermic (41.5 - 42.5°C) cisplatin and doxorubicin combined with the infusion of systemic ifosfamide chemotherapy. Using high pressure liquid chromatography (HPLC) the concentrations of ifosfamide and 4-hydroxyifosfamide were determined in plasma, peritoneal fluid, urine, and when possible, within small tumor nodules less than 1 cm.
Urine ifosfamide and 4-hydroxyifosfamide concentrations exceeded those within the plasma and peritoneal fluid throughout the 90 minutes of drug infusion. Plasma concentrations of ifosfamide exceeded peritoneal fluid levels of ifosfamide during the 90 minutes of chemotherapy infusion; however, at 60 minutes after infusion ceased, the peritoneal fluid and plasma concentrations were equivalent. Both ifosfamide and 4-hydroxyifosfamide could be recovered from peritoneal tumor nodules throughout the 90 minutes of ifosfamide continuous infusion and exceeded plasma concentrations.
Clear understanding of the pharmacology of perioperative intraperitoneal hyperthermia combined with systemic chemotherapy may provide important information for the design of treatment regimens. 4-hydroxyifosfamide within cancerous tissue suggested a favorable pharmacologic endpoint in the study of ifosfamide administered in the operating room.
Place, publisher, year, edition, pages
2011. 185092- p.
Medical and Health Sciences
IdentifiersURN: urn:nbn:se:uu:diva-133274DOI: 10.1155/2011/185092OAI: oai:DiVA.org:uu-133274DiVA: diva2:360824