An Approach to the Therapy of Metastases from Cancer of the Upper Rectum: A Working Hypothesis

Abstract

Previously reported analyses of autopsy data gathered from patients dying from the sequelae of adenocarcinomas of the upper rectum revealed a step-wise sequence in the development of distant metastases. First, dissemination via the portal vein led to secondary hepatic metastases. Cancer cells from these liver metastases (not the primary cancer) disseminated via the inferior vena cava to generate tertiary pulmonary metastases. Cancer cells from the lung metastases (not the primary or secondary cancers) then disseminated via the arterial route to give rise to metastases in other organs. We propose a protocol for the treatment of patients with upper rectal carcinomas, based on the expectation that, at different times after diagnosis, some patients will have no distant metastases, metastases in the liver only, or in the liver and lungs only. The protocol for therapy is based on currently available liposome technology, by means of which high doses of drugs can be targeted to the liver and lungs containing the metastases, yet distinct from the metastases. It is argued that selective local delivery of this type would increase the dose of cytotoxic agent delivered, thereby increasing the chances of overcoming the relative drug-resistance of the metastatic cancer cells and, at the same time, reduce the risk of nonspecific toxicity. Liver and lung-selective liposomes could, when necessary, be delivered at the same time, in the same systemic venous infusion.