Intraperitoneal spread of gastrointestinal malignancies is a significant clinical problem and contributes to an incidence of distant relapse as high as 30% in gastric cancer. Local dissemination of tumour cells into the peritoneal cavity determines the outcome in advanced gastric cancer and diffuse-type carcinoma, and patients with negative peritoneal washings have a more favourable prognosis. Extensive lymph node dissection has been shown (by quantitative reverse transcription-polymerase chain reaction for carcinoembryonic antigen and cytokeratin 20 combined with extensive intraoperative peritoneal lavage¹) to open lymphatic channels and spread viable cancer cells into the peritoneal cavity. Hence patient subpopulations that might benefit from intraperitoneal therapy regimens may be identified.

Malignant disease localised within the abdominal cavity has been a target for the staged development of clinical gene therapy approaches because of the smaller doses of experimental agent and increased safety margins over systemic administration. There has been extensive—and safe—experience of p53 gene therapy which culminated in a randomised phase III trial in which women with p53 null or p53 mutant ovarian cancer were randomised to chemotherapy alone or chemotherapy plus intraperitoneal Ad p53 following optimum debulking primary surgery. However, the first interim analysis indicated that not only did Ad p53 fail to improve effectiveness but it was also associated with increased toxicity. As a result, the study has been abandoned (reported in Zeimet and Marth²). Two broad possibilities exist to explain why the trials were relatively unsuccessful. Firstly, there is the perennial problem of suboptimal gene transfer. Secondly, there is the possibility that p53 is the “wrong” transgene. Although p53 mutations are found in many malignancies³ and defective p53 function may be causally linked to chemotherapy resistance,⁴ many …