Inhibition of fluorouracil-induced stomatitis by oral cryotherapy

J Clin Oncol. 1991 Mar;9(3):449-52. doi: 10.1200/JCO.1991.9.3.449.


Mucositis is a significant dose-limiting toxicity associated with fluorouracil (5FU), particularly when it is combined with leucovorin. We hypothesized that oral cryotherapy would cause local vasoconstriction and would temporarily decrease blood flow to the oral mucous membranes. If cryotherapy were used during the time of peak serum 5FU levels, then the oral mucous membranes would have less exposure to 5FU and thus develop less mucositis. To test this hypothesis, 95 patients scheduled to receive their first cycle of 5FU plus leucovorin were randomized to have oral cryotherapy at the time of chemotherapy administration or to serve as a control group. Subsequent mucositis was significantly reduced in the group assigned to receive cryotherapy as judged by the attending physicians (P = .0002) and by the patients themselves (P = .0001). We now routinely recommend this cryotherapy procedure for our patients receiving daily bolus 5FU plus leucovorin.

Publication types

  • Clinical Trial
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Administration, Oral
  • Cryosurgery / methods*
  • Drug Synergism
  • Fluorouracil / adverse effects*
  • Fluorouracil / antagonists & inhibitors
  • Humans
  • Leucovorin / pharmacology*
  • Mouth Mucosa
  • Prospective Studies
  • Smoking
  • Stomatitis / chemically induced*
  • Stomatitis / prevention & control


  • Leucovorin
  • Fluorouracil