title: Prospective phase I evaluation of radiation therapy, 5-fluorouracil, and levamisole in locally advanced gastrointestinal cancer.
abstract: OBJECTIVE
  A recent clinical trial in patients with resected node-positive colon cancer demonstrated a clear survival advantage for patients treated with adjuvant 5-fluorouracil and levamisole. This finding led to interest in development of a Phase III trial comparing 5-fluorouracil and levamisole with 5-fluorouracil, levamisole, and radiation therapy in colon cancer patients at high risk for local recurrence. A prospective evaluation of 5-fluorouracil, levamisole, and radiation therapy was undertaken with the goal of establishing a satisfactorily tolerated regimen.
  
  
  METHODS
  Fifteen patients were studied who had locally advanced or locally recurrent upper abdominal gastrointestinal cancer (11 patients) or large bowel cancer confined to the pelvis (4 patients). The tumor and regional lymph nodes received 45 Gy in 25 fractions. Patients with pelvic tumors subsequently were treated with a radiation boost of 5.4-9 Gy in 3-5 fractions. Systemic therapy consisted of 5-fluorouracil, 450 mg/m2, given intravenously for 3 consecutive days during the first and last weeks of radiation therapy. Levamisole, 50 mg, given orally 3 times daily was used for 3 consecutive days concurrent with initiation of radiation therapy and 5-fluorouracil, at the beginning of the third week of radiation therapy, and concurrent with the final 3-day course of 5-fluorouracil.
  
  
  RESULTS
  Therapy was generally well tolerated. In two patients, > or = grade 3 nonhematologic toxicity developed and consisted of transient small bowel obstruction in one and severe nausea and vomiting related to levamisole administration in another. One patient experienced grade 3 hematologic toxicity with a leukocyte count nadir of 1,600 cells/microL.
  
  
  CONCLUSIONS
  These results are similar to the toxicity profile reported elsewhere for radiation therapy and 5-fluorouracil. The addition of levamisole to radiation therapy and 5-fluorouracil does not appear to increase toxicity significantly.
authors.affiliation: Division of Radiation Oncology, Mayo Clinic, Rochester, MN 55905.
authors.forename: J A
authors.initials: JA
authors.lastname: Martenson
authors.forename: A J
authors.initials: AJ
authors.lastname: Schutt
authors.forename: G L
authors.initials: GL
authors.lastname: Grado
authors.forename: W J
authors.initials: WJ
authors.lastname: Maples
authors.forename: R F
authors.initials: RF
authors.lastname: Marschke
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D003131:Combined Modality Therapy; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects; D005770:Gastrointestinal Neoplasms / Q000628:therapy*; D006801:Humans; D007978:Levamisole / Q000008:administration & dosage / Q000009:adverse effects; D011446:Prospective Studies; D011878:Radiotherapy / Q000009:adverse effects
chemical_list: D007978:Levamisole; D005472:Fluorouracil