Comparison of Adjuvant Chemotherapy Regimens in Treating Stage II/III Rectal Cancer

1. Group I (Pre-operative) Registration

   Inclusion Criteria:
   * Patients must have histologically proven adenocarcinoma of the rectum with no distant metastases. Clinical staging is required (T3N0M0, T4N0M0, TanyN1-3M0).
   * Patients must not have evidence of tumor outside of the pelvis including liver metastases, peritoneal seeding, or metastatic inguinal lymphadenopathy.
   * The distal border of the tumor must be at or below the peritoneal reflection, defined as within 12 cm of anal verge by proctoscopic examination. In addition, patients who have had a portion of their tumors confirmed to be below the peritoneal reflection at the time of surgery are eligible regardless of the distance determined by endoscopy.
   * Transmural penetration of tumor through the muscularis propria must be demonstrated by CT scan, endo-rectal ultrasound or MRI.
   * Tumors must be defined prospectively by the surgeon as clinically resectable or not.

     * Clinically resectable tumors will be defined by the surgeon as not fixed and completely resectable with negative margins based on the routine examination of the non-anesthetized patient.
     * Before pre-op treatment, the surgeon should estimate and record the type of resection anticipated: APR, LAR or LAR/coloanal anastomosis.
   * The tumor may be clinically fixed or initially not completely resectable, clinical stage T4 N0-2 M0 based on the presence of at least one of the following criteria:

     * Clinically fixed tumors on rectal examination with tumor adherent to the pelvic sidewall or sacrum.
     * Hydronephrosis on CT scan or IVP or ureteric or bladder invasion as documented by cystoscopy and cytology or biopsy, or invasion into prostate.
     * Vaginal or uterine involvement.
   * Patients must not have a previous or concurrent malignancy, with the exception of:

     * Nonmelanoma skin cancer or in situ cervical cancer.
     * Treated non-pelvic cancer from which the patient has been continuously disease-free for \>5 years.
   * Patients must have ECOG performance status 0-1.
   * Patients must be \> 18 years of age.
   * All females of childbearing potential must have a blood or urine test within 2 weeks prior to registration to rule out pregnancy.
   * Sexually-active women of childbearing potential and sexually active males are strongly advised to use an accepted and effective method of contraception

   Exclusion Criteria:
   * Patients have received prior chemotherapy or pelvic irradiation therapy.
   * Female patients must not be pregnant or breast-feeding.
   * Patients have an active inflammatory bowel disease or other serious medical illness which might limit the ability of the patient to receive protocol therapy.
2. Group II (Post-operative) Registration

   Inclusion Criteria:
   * Patients must have had histologically proven adenocarcinoma of the rectum with no distant metastases. Pathologic staging is required (T3N0M0, T4N0M0, TanyN1-3M0).
   * Patients must not have evidence of tumor outside of the pelvis including liver metastases, peritoneal seeding, or metastatic inguinal lymphadenopathy.
   * The distal border of the tumor must have been at or below the peritoneal reflection, defined as within 12 centimeters of anal verge by proctoscopic examination. In addition, patients who have had a portion of their tumors confirmed to be below the peritoneal reflection at the time of the surgery are eligible regardless of the distance determined by endoscopy.
   * Patients must not have received prior chemotherapy or pelvic irradiation therapy.
   * Patients must not have a previous or concurrent malignancy, with the exception of:

     * Non-melanoma skin cancer or in situ cervical cancer.
     * Treated non-pelvic cancer from which the patient has been continuously disease-free for \>5 years.
   * Patients must have ECOG performance status 0-1.
   * Patients must be \> 18 years of age.
   * All females of childbearing potential must have a blood or urine test within 2 weeks prior to registration to rule out pregnancy.
   * Sexually active women of childbearing potential and sexually active males are strongly advised to use an accepted and effective method of contraception.

   Exclusion Criteria:
   * Patients have an active inflammatory bowel disease or other serious medical illness which might limit the ability of the patient to receive protocol therapy.
   * Female patients are pregnant or breast-feeding.
3. Randomization (Groups I and II)

Inclusion Criteria:

* Patients must have a completely resected tumor and be within 21-56 days from the date of surgery.
* Patients who received combination chemotherapy/XRT prior to randomization (Group I) must have had a minimum radiation dose of 50.4 Gy.
* Patients must have ECOG performance status 0-1.
* Patients must have adequate renal function (creatinine \< 1.5 x ULN) obtained \< 4 weeks prior to randomization.
* Patients must have adequate hepatic function (bilirubin \< 1.5 x ULN, SGOT (AST) \< 3 x ULN) obtained \< 4 weeks prior to randomization).
* Patients must have absolute neutrophil count \> 1500/mm3 and platelet count \> 100,000/mm3 \< 4 weeks prior to randomization.

Exclusion Criteria:

• Patients have an active inflammatory bowel disease or other serious medical illness which might limit the ability of the patient to receive protocol therapy.