The administration of
antineoplastic agents directly into the peritoneal cavity as treatment of localised
cancer is based on sound pharmacokinetic principles. This unique technique has to the potential to optimise outcome in settings where preclinical and clinical data suggest that cytotoxicity of a specific
drug against a particular tumour type is enhanced by either increasing the
drug concentration or duration of exposure. Phase I trials have confirmed the safety and pharmacokinetic advantage for a number of agents delivered by the intraperitoneal relative to the systemic route, including
cisplatin (10- to 20-fold advantage for regional delivery),
carboplatin (10- to 20-fold advantage), and
paclitaxel (1,000-fold advantage). In phase II trials, performed mostly in patients with
ovarian cancer, this approach has achieved objective responses in settings where intravenous
drug delivery has not achieved the desired effect (e.g. surgically documented complete response using intraperitoneal
cisplatin as second-line
therapy of
ovarian cancer). Phase III trials employing intraperitoneal
cisplatin as initial treatment of small volume advanced
ovarian cancer have demonstrated that regional
therapy results in a modest, but statistically significant, improvement in both progression-free and overall survival compared to intravenous
cisplatin. Further exploration of this novel method of treatment, including the conduct of definitive randomised phase III clinical trials, is indicated in
ovarian cancer and in other tumour types where clinical manifestations are principally localised to the peritoneal cavity.