The non-invasive monitoring of low dose, infusional 5-fluorouracil and its modulation by interferon-alpha using in vivo 19F magnetic resonance spectroscopy in patients with colorectal cancer: a pilot study.
BACKGROUND
5-Fluorouracil (5-FU) is the most widely used cytotoxic drug 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 varying the delivery schedule and combining it with modulators. With the development of whole body magnetic resonance systems it is now possible 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.


METHODS
Magnetic Resonance Spectroscopy (MRS) was used to non-invasively monitor the metabolism of 5-FU in the liver metastases 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 with 5-FU, 11 (42%) achieving partial response. Of the 15 given interferon when disease became refractory to 5-FU, 4 showed signs of further response. In patients observed by MRS during the first 8 weeks of 5-FU treatment, those with a visible 5-FU signal were likely to respond to treatment (p = 0.017). At the time of interferon-alpha addition, MRS showed that 7 patients developed new or increased 5-FU signals, and 4 patients showed a signal from the active metabolites of 5-FU. The patients who exhibited a new or increased 5-FU signal were more likely to show further response to interferon-alpha (p = 0.007).


CONCLUSIONS
MRS is a powerful technique for monitoring intratumoural metabolism and modulation of 5-FU enabling prediction of tumour outcome. Direct metabolic information may facilitate the rapid development of optimal clinical schedules 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 metabolism of a fluorinated drug is of interest.
Findlay
M P
MP
CRC Section of Medicine, Royal Marsden Hospital, Sutton, Surrey, United Kingdom.
Leach
M O
MO
Cunningham
D
D
Collins
D J
DJ
Payne
G S
GS
Glaholm
J
J
Mansi
J L
JL
McCready
V R
VR
D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D015179:Colorectal Neoplasms / Q000188:drug therapy*; D004334:Drug Administration Schedule; D016903:Drug Monitoring / Q000379:methods*; D005462:Fluorine Radioisotopes; D005472:Fluorouracil / Q000008:administration & dosage / Q000378:metabolism*; D006801:Humans; D016898:Interferon-alpha / Q000008:administration & dosage; D008113:Liver Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000556:secondary*; D009682:Magnetic Resonance Spectroscopy; D010865:Pilot Projects
D005462:Fluorine Radioisotopes; D016898:Interferon-alpha; D005472:Fluorouracil