Phase I Study of Preoperative Radiation Therapy With Concurrent Protracted Continuous Infusion 5-FU and Dose Escalating Oxaliplatin Followed by Surgery, 5-FU, and Leucovorin for Locally Advanced (T3 and T4) Rectal Adenocarcinoma

Study start date: May 1, 1999

Inclusion Criteria: Histologically confirmed, locally advanced, non-metastatic primary T3 or T4 primary adenocarcinoma of the rectum No evidence of tumor outside of the pelvis including liver metastases, peritoneal seeding, or metastatic inguinal lymphadenopathy No intra-operative radiotherapy (IORT) or brachytherapy will be allowed The distal border of the tumor must be at or below the peritoneal reflection, defined as within 12 centimeters of anal verge by proctoscopic examination Transmural penetration of tumor through the muscularis propria must be demonstrated by either of the following: CT scan plus endorectal 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 mobile 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 Sciatica attributed to sacral root invasion with CT scan/MRI evidence of the lack of clear tissue plane will be considered evidence of fixation 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 ECOG performance status 0-2 and surgical evaluation confirms the patient's medical condition would tolerate the proposed surgical procedure Caloric intake should be >= 1500 kilocalories/d WBC >= 3500/uL Platelets >= 100,000/uL Serum creatinine =< 2.0 mg/dL Serum bilirubin less than 2.0 mg/dL Alk Phos =< 2 x ULN SGOT =< 2 x ULN CEA should be determined prior to initiation of therapy Absence of clinical evidence of high-grade (lumen diameter < 1cm) large bowel obstruction, unless diverting colostomy has been performed Pregnant or lactating women are not eligible Women of childbearing potential and sexually active males are strongly advised to use an accepted and effective method of contraception No prior chemotherapy or pelvic irradiation therapy No previous or concurrent malignancy is allowed, except: Nonmelanoma skin cancer or in situ cervical cancer Treated non-pelvic cancer from which the patient has been continuously disease free more than five years No active inflammatory bowel disease or other serious medical illness which might limit the ability of the patient to receive protocol therapy