Intraperitoneal drug delivery of antineoplastics

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.