Phase II trial of preoperative 3D conformal radiotherapy, protracted venous infusion 5-fluorouracil, and weekly CPT-11, followed by surgery for ultrasound-staged T3 rectal cancer

Vivek K. Mehta*, Cheryl Cho, James M. Ford, C. Jambalos, Joseph Poen, Albert Koong, Albert Lin, J. Augusto Bastidas, Harvey Young, Eamonn P. Dunphy, George Fisher

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

124 Scopus citations

Abstract

Purpose: CPT-11 sensitizes tumor cells to radiation and in combination therapy with 5-fluorouracil (5-FU) results in enhanced cytotoxicity to metastatic colorectal cancer. We report the results from a Phase II trial of preoperative radiotherapy (RT), CPT-11, and 5-FU for patients with ultrasound-staged T3 rectal cancer. Methods and Materials: Between April 1999 and August 2001, 32 patients (21 men, 11 women; median age 52 years, range 40-74) with biopsy-proven adenocarcinoma of the rectum were enrolled in the study. All patients underwent endorectal ultrasonography for staging (uT3N0 = 19; uT3N1 = 13; uT2N1 = 1). RT was prescribed to the draining lymph nodes (45 Gy in 1.8-Gy daily fractions) and tumor (50.4 Gy in 1.8-Gy daily fractions). Patients also received concurrent CPT-11 (50 mg/m2, Days 1, 8, 15, and 22) and 5-FU (200 mg/m2 daily, 7 d/wk, Days 1-33). Surgical resection was performed 6-10 weeks after completing chemoradiotherapy. Results: Acute toxicity was frequently observed, and 18 patients (56%) required either a chemotherapy dose reduction or RT interruption of >3 days. One patient withdrew because of diarrhea and abdominal cramping (Grade III) after 10 days of treatment. Although no Grade IV toxicity was observed, Grade III diarrhea (n = 9, 28%), mucositis (n = 7, 21%), rectal sores (n = 7, 21%), abdominal cramping (n = 3, 9%) were noted. Of the 32 patients who underwent surgery, 12 had a complete pathologic response. Of the 32 patients, the disease of 23 (71%) was downstaged. The average length of hospitalization was between 5 and 12 days, with 1 patient staying 33 days. All patients were followed for disease-free survival. Conclusion: Although associated with frequent acute toxicity, the regimen is associated with significant tumor "downstaging." Additional patients and longer follow-up are necessary to define the role of this regimen fully.

Original languageEnglish
Pages (from-to)132-137
Number of pages6
JournalInternational Journal of Radiation Oncology Biology Physics
Volume55
Issue number1
DOIs
StatePublished - 1 Jan 2003
Externally publishedYes

Keywords

  • 5-Fluorouracil
  • CPT-11
  • Chemoradiotherapy
  • Neoadjuvant
  • Preoperative
  • Protracted venous infusion
  • Radiotherapy
  • Rectal cancer

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