title: Pre-operative combined 5-FU, low dose leucovorin, and sequential radiation therapy for unresectable rectal cancer.
abstract: OBJECTIVE
  We performed a Phase I trial to determine the maximum tolerated dose of combined pre-operative radiation (5040 cGy) and 2 cycles (bolus daily x 5) of 5-FU and low dose LV (20 mg/m2), followed by surgery and 10 cycles of post-operative LV/5-FU in patients with unresectable primary or recurrent rectal cancer.
  
  
  METHODS
  Twelve patients were entered. The initial dose of 5-FU was 325 mg/m2. 5-FU was to be escalated while the LV remained constant at 20 mg/m2. Chemotherapy began on day 1 and radiation on day 8. The post-operative chemotherapy, was not dose escalated; 5-FU: 425 mg/m2 and LV: 20 mg/m2. The median follow-up was 14 months (7-16 months).
  
  
  RESULTS
  Following pre-operative therapy, the resectability rate with negative margins was 91% and the pathologic complete response rate was 9%. For the combined modality segment (preoperative) the incidence of any grade 3+ toxicity was diarrhea: 17%, dysuria: 8%, mucositis: 8%, and erythema: 8%. The median nadir counts were WBC: 3.1, HGB: 8.8, and PLT: 153,000. The maximum tolerated dose of 5-FU for pre-operative combined LV/5-FU/RT was 325 mg/m2 with no escalation possible. Therefore, the recommended dose was less than 325 mg/m2.
  
  
  CONCLUSIONS
  Since adequate doses of 5-FU to treat systemic disease could not be delivered until at least 3 months (cycle 3) following the start of therapy, we do not recommend that this 5-FU, low dose LV, and sequential radiation therapy regimen be used as presently designed. However, given the 91% resectability rate we remain encouraged with this approach.
authors: Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, NY 10021.
authors: B D
authors: BD
authors: Minsky
authors: A M
authors: AM
authors: Cohen
authors: N
authors: N
authors: Kemeny
authors: W E
authors: WE
authors: Enker
authors: D P
authors: DP
authors: Kelsen
authors: G
authors: G
authors: Schwartz
authors: L
authors: L
authors: Saltz
authors: J
authors: J
authors: Dougherty
authors: J
authors: J
authors: Frankel
authors: J
authors: J
authors: Wiseberg
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D003131:Combined Modality Therapy; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage*; D006801:Humans; D002955:Leucovorin / Q000008:administration & dosage*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D011878:Radiotherapy / Q000009:adverse effects; D012004:Rectal Neoplasms / Q000188:drug therapy / Q000532:radiotherapy / Q000601:surgery / Q000628:therapy*
chemical_list: D002955:Leucovorin; D005472:Fluorouracil