Intraperitoneal drug delivery of antineoplastics

The administration of antineoplastic agents directly into the peritoneal ca vity as treatment of localised cancer is based on sound pharmacokinetic pri nciples. 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 incre asing 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 systemi c route. including cisplatin (10- to 20-fold advantage for regional deliver y), carboplatin (10- to 20-fold advantage), and paclitaxel (1000-fold advan tage). In phase II trials. performed mostly in patients with ovarian cancer , this approach has achieved objective responses in settings where intraven ous drug delivery has not achieved the desired effect (e.g. surgically docu mented complete response using intraperitoneal cisplatin as second-line the rapy of ovarian cancer). Phase III trials employing intraperitoneal cisplat in as initial treatment of small volume advanced ovarian cancer have demons trated that regional therapy results in a modest, but statistically signifi cant, improvement in both progression-free and overall survival compared to intravenous cisplatin. Further exploration of this novel method of treatment, including the conduc t of definitive randomised phase III clinical trials, is indicated in ovari an cancer and in other tumour types where clinical manifestations are princ ipally localised to the peritoneal cavity.