Metronomic Chemotherapy Was Originally Designed and First Used in 1994 for Early Stage Cancer -- Why Is It Taking So Long to Proceed?

Abstract

This is a personal case history from a researcher who was studying tumor growth when diagnosed in 1994 with stage IIIc colon cancer. The risk of relapse was 80% without therapy and 50% with conventional therapy. However his previous research led him to challenge the idea that tumor growth was described by the Gompertz equation. This is the fundamental theory underlying the concept that adjuvant chemotherapy should be started as soon as possible after primary surgery and should be administered at maximum tolerated dose and repeated when the patient’s immune system recovers from the last course of therapy. It turns out that Gompertz growth is based on a study by Laird in the 1960s that consisted of measuring tumor growth on 18 rodents and one rabbit. On the basis of those data and a fundamental mathematical error, Laird claimed “The pattern of growth defined by the Gompertz equation appears to be a general biological characteristic of tumor growth.” But then if the Gompertz equation assumption is wrong, how should adjuvant therapy be given? Patient/researcher opted for a low dose long term continuous infusion therapy with the mainstay colon cancer drug 5-flourouracil. This therapy had previously been used in late stage disease but never in early stage disease. Patient used this non-toxic therapy 6 hours a night for 2.5 years. Patient was on the staff of Judah Folkman and after discussing this with Folkman, oncologist-researcher Tim Browder tested low dose long term continuous infusion 5- fluorouracil to determine if it is antiangiogenic. It was found to be so. This therapy is now called metronomic chemotherapy and is slowly being tested in laboratory, clinical and veterinary situations. Patient/researcher remains disease free 17 years later and asks why it is taking so long to proceed.