Phase III Randomized Study of Preoperative vs Postoperative 5-FU/CF/Radiotherapy in Patients with Operable Adenocarcinoma of the Rectum

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Alternate Title

Chemotherapy and Radiation Therapy Before or After Surgery in Treating Patients With Rectal Cancer That Can Be Surgically Removed

Basic Trial Information

PhaseTypeStatusAgeSponsorProtocol IDs
Phase IIITreatmentCompleted18 to 76NCINSABP-R-03


I.  Compare disease-free and overall survival in patients with operable 
carcinoma of the rectum treated with preoperative vs. postoperative 

II.  Compare the local recurrence rates in patients treated with these 2 

III.  Evaluate the response of rectal tumors to preoperative 
chemoradiotherapy, and correlate response with disease-free and overall 

IV.  Assess the down-staging effect of preoperative chemoradiotherapy on tumor 
size and pathologic status of regional lymph nodes.

V.  Estimate the proportion of patients receiving preoperative 
chemoradiotherapy who can be converted to sphincter-saving surgery from 
abdominoperineal resection and of those who can be converted from 
sphincter-saving surgery to local excision alone.

Entry Criteria

Disease Characteristics:

Histologically proven, resectable, invasive rectal adenocarcinoma

  Tumor palpable on rectal exam or accessible endoscopically
     Distal border no more than 15 cm from anal verge

  Diagnosis by surgical or endoscopic biopsy required
     Majority of tumor must remain after biopsy
     No excisional biopsy

  Resectability based on:
     Tumor moveable on clinical exam without fixation to pelvis or adjacent
     organs beyond limits of exenteration

     Enlarged perirectal or pelvic lymph nodes must not be fixed to pelvis

  No radiographic evidence of metastasis
     Abdominopelvic CT with biopsy of suspicious areas required

  Intestinal obstruction allowed provided only treatment is decompressing

  Free perforation (free air or fluid in abdomen) not eligible
     Walled-off perforation allowed

  Synchronous rectal lesions allowed

  No synchronous colon tumors

No histology other than adenocarcinoma

Treatment must begin within 49 days of histologic diagnosis

Prior/Concurrent Therapy:

No prior therapy for rectal cancer except an incisional diagnostic biopsy and
a preliminary decompression colostomy

Patient Characteristics:

  18 to 76

Performance status:

Life expectancy:
  At least 10 years excluding the cancer

  WBC at least 4,000
  Platelets at least 100,000

  Bilirubin no greater than 1.5 times normal
  AST or ALT no greater than 1.5 times normal
  No hepatic disease that would preclude treatment

  Creatinine no greater than 1.5 times normal
  No renal disease that would preclude treatment

  No cardiovascular disease that would preclude treatment

  No active inflammatory bowel disease
  No nonmalignant systemic disease that would preclude treatment
  No psychiatric or addictive disorder that would preclude informed consent
  No prior or concurrent second malignancy except:
     Nonmelanomatous skin cancer
     Adequately treated in situ cervical cancer
  No pregnant women

Expected Enrollment

It is anticipated that 180 patients/year will be accrued for 5 years.  Interim 
analyses will be conducted q 6 months beginning 2.5 years into the study; if a 
significant survival benefit is seen in one arm, the study may close early.


Randomized study.

Arm I:  Single-Agent Chemotherapy with Drug Modulation followed by 
Radiotherapy plus Single-Agent Chemotherapy/Radiosensitization with Drug 
Modulation followed by Surgery followed by Single-Agent Chemotherapy with Drug 
Modulation.  Fluorouracil, 5-FU, NSC-19893; with Leucovorin calcium, CF, 
NSC-3590; followed by pelvic irradiation with megavoltage equipment (minimum 
energies at least 4 MV, Co60); plus 5-FU/CF; followed by tumor excision; 
followed by 5-FU/CF.

Arm II:  Surgery followed by Single-Agent Chemotherapy with Drug Modulation 
followed by Radiotherapy plus Single-Agent Chemotherapy/Radiosensitization 
with Drug Modulation followed by Single-Agent Chemotherapy with Drug 
Modulation.  Tumor excision; followed by 5-FU/CF; followed by pelvic 
irradiation as in Arm I; plus 5-FU/CF; followed by 5-FU/CF.

Published Results

Roh MS, Colangelo LH, O'Connell MJ, et al.: Preoperative multimodality therapy improves disease-free survival in patients with carcinoma of the rectum: NSABP R-03. J Clin Oncol 27 (31): 5124-30, 2009.[PUBMED Abstract]

Hyams DM, Mamounas EP, Petrelli N, et al.: A clinical trial to evaluate the worth of preoperative multimodality therapy in patients with operable carcinoma of the rectum: a progress report of National Surgical Breast and Bowel Project Protocol R-03. Dis Colon Rectum 40 (2): 131-9, 1997.[PUBMED Abstract]

Trial Contact Information

Trial Lead Organizations

National Surgical Adjuvant Breast and Bowel Project

Norman Wolmark, MD, Protocol chair
Ph: 412-359-3336; 866-680-0004

Note: The purpose of most clinical trials listed in this database is to test new cancer treatments, or new methods of diagnosing, screening, or preventing cancer. Because all potentially harmful side effects are not known before a trial is conducted, dose and schedule modifications may be required for participants if they develop side effects from the treatment or test. The therapy or test described in this clinical trial is intended for use by clinical oncologists in carefully structured settings, and may not prove to be more effective than standard treatment. A responsible investigator associated with this clinical trial should be consulted before using this protocol.