Body composition as an independent determinant of 5-fluorouracil-based chemotherapy toxicity.
OBJECTIVE
Evidence suggests that lean body mass (LBM) may be useful to normalize doses of chemotherapy. Data from a prospective study were used to determine if the highest doses of 5-fluorouracil (5-FU) per kilogram LBM would be associated with dose-limiting toxicity in stage II/III colon cancer patients treated with 5-FU and leucovorin.


METHODS
Toxicity after cycle 1 was graded according to National Cancer Institute Common Toxicity Criteria, version 2.0. Muscle tissue was measured by computerized tomography. An extrapolation to the LBM compartment of the whole body was employed.


RESULTS
Mean values of 5-FU/LBM of the entire population were different in terms of presence or absence of toxicity (P = 0.036). A cut point of 20 mg 5-FU/kg LBM seemed to be a threshold for developing toxicity (P = 0.005). This observation was pertinent to women (odds ratio, 16.73; P = 0.021). Women in this study had a relatively low proportion of LBM relative to their body surface area.


CONCLUSIONS
Our study shows that low LBM is a significant predictor of toxicity in female patients administered 5-FU using the convention of dosing per unit of body surface area. We conclude that variation in toxicity between females and males may be partially explained by this feature of body composition.
Prado
Carla M M
CM
Department of Oncology, University of Alberta, Edmonton, Alberta, Canada.
Baracos
Vickie E
VE
McCargar
Linda J
LJ
Mourtzakis
Marina
M
Mulder
Karen E
KE
Reiman
Tony
T
Butts
Charles A
CA
Scarfe
Andrew G
AG
Sawyer
Michael B
MB
D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000633:toxicity*; D001823:Body Composition; D015992:Body Mass Index; D001830:Body Surface Area; D004305:Dose-Response Relationship, Drug; D005260:Female; D005472:Fluorouracil / Q000494:pharmacology* / Q000633:toxicity*; D006801:Humans; D002955:Leucovorin / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012737:Sex Factors
D000970:Antineoplastic Agents; D002955:Leucovorin; D005472:Fluorouracil