Preoperative treatment of patients with locally advanced unresectable rectal adenocarcinoma utilizing continuous chronobiologically shaped 5-fluorouracil infusion and radiation therapy

Cancer. 1996 Jul 15;78(2):217-25. doi: 10.1002/(SICI)1097-0142(19960715)78:2<217::AID-CNCR5>3.0.CO;2-I.


Background: This study was designed to determine the efficacy and maximally tolerated dose of 5-fluorouracil when administered by chronobiologically shaped prolonged infusion in combination with radiation therapy in patients with both locally advanced and unresectable rectal carcinoma.

Methods: Eighteen sequential patients determined clinically to have either locally advanced or unresectable rectal carcinoma were treated by 4500 centigray (cGy) or 5580 cGy, respectively, combined with continuous chronobiologically modulated 5-FU infusion starting at 250 mg/m2/day, with the dose escalating in each cohort of 5 patients if no Grade 3 or higher toxicity was observed in each cohort. Imaging studies were obtained prior to and after completion of treatment.

Results: All 18 patients completed the full course of radiation therapy and all were subsequently resectable for potential cure. The maximum tolerated dose of 5-FU was 275/m2/day for 5 weeks. Seven patients had a sphincter-sparing procedure, and ten patients underwent an abdominoperineal resection, all with clear margins. Five complete pathologic responses (28%) were obtained. The average follow-up time was 12 months with a range of 6 to 37 months. With the exception of two patients, one of whom declined surgery and one of whom died of widespread disease, all of the patients have remained free of disease.

Conclusions: The combination of radiation therapy and continuous chronobiologically shaped 5-FU infusion at a dose of up to 275/m2/day is well tolerated and appears to be more effective in downsizing and possibly downstaging locally advanced and unresectable rectal carcinoma than radiation therapy alone. Longer follow-up will determine whether ultimate disease free and overall survival are improved by this method.

MeSH terms

  • Adenocarcinoma / drug therapy*
  • Adenocarcinoma / radiotherapy*
  • Adenocarcinoma / surgery
  • Adult
  • Aged
  • Anal Canal / surgery
  • Antimetabolites, Antineoplastic / administration & dosage
  • Antimetabolites, Antineoplastic / therapeutic use*
  • Cohort Studies
  • Combined Modality Therapy
  • Disease-Free Survival
  • Drug Tolerance
  • Female
  • Fluorouracil / administration & dosage
  • Fluorouracil / therapeutic use*
  • Follow-Up Studies
  • Humans
  • Infusions, Intravenous
  • Male
  • Middle Aged
  • Preoperative Care
  • Radiotherapy Dosage
  • Rectal Neoplasms / drug therapy*
  • Rectal Neoplasms / radiotherapy*
  • Rectal Neoplasms / surgery
  • Remission Induction
  • Survival Rate


  • Antimetabolites, Antineoplastic
  • Fluorouracil