THE NONINVASIVE MONITORING OF LOW-DOSE, INFUSIONAL 5-FLUOROURACIL ANDITS MODULATION BY INTERFERON-ALPHA USING IN-VIVO F-19 MAGNETIC-RESONANCE SPECTROSCOPY IN PATIENTS WITH COLORECTAL-CANCER - A PILOT-STUDY

Background: 5-Fluorouracil (5-FU) is the most widely used cytotoxic dr ug in oncology and the only one useful in the management of colorectal cancer - a leading cause of cancer death worldwide. Recent studies of 5-FU have focused on increasing efficacy and reducing toxicity by var ying the delivery schedule and combining it with modulators. With the development of whole body magnetic resonance systems it is now possibl e to examine the metabolism of 5-FU in vivo by exploiting the magnetic properties of the fluorine atom which is an integral component of the drug. Patients and methods: Magnetic Resonance Spectroscopy (MRS) was used to non-invasively monitor the metabolism of 5-FU in the liver me tastases of colorectal cancer patients. The patients were treated with a continuous low dose intravenous infusion of 5-FU until the point of refractory disease, at which time interferon-alpha was added with the objective of modulating 5-FU activity. MRS was performed at specific phases of the treatment. Results: Twenty-six patients were treated wit h 5-FU, 11 (42%) achieving partial response. Of the 15 given interfero n when disease became refractory to 5-FU, 4 showed signs of further re sponse. In patients observed by MRS during the first 8 weeks of 5-FU t reatment, those with a visible 5-FU signal were likely to respond to t reatment (p = 0.017). At the time of interferon-a addition, MRS showed that 7 patients developed new or increased 5-FU signals, and 4 patien ts showed a signal from the active metabolites of 5-FU. The patients w ho exhibited a new or increased 5-FU signal were more likely to show f urther response to interferon-alpha (p = 0.007). Conclusions: MRS is a powerful technique for monitoring intratumoural metabolism and modula tion of 5-FU enabling prediction of tumour outcome. Direct metabolic i nformation may facilitate the rapid development of optimal clinical sc hedules for 5-FU and its modulators, thus maximising antitumour effect and minimising toxicity to the patient. This technique may be applied to other areas of clinical medicine where knowledge of the tissue met abolism of a fluorinated drug is of interest.