Neo-adjuvant Chemoradiation With Oxaliplatin/5-FU in Rectal Cancer

A Phase II Open-labeled, Prospective Study to Determine the Efficacy of Preoperative Chemoradiation With Oxaliplatin/5-FU in Locally Advanced Rectal Cancer Followed by Total Mesorectal Excision and FOLFOX6

RATIONALE: 5FU based neoadjuvant chemoradiation (nCRT) is the standard of care for Stage II/III rectal cancer. Pathologic complete response (pCR) and downstaging have been associated with improved outcomes. The addition of oxaliplatin (OXA) to neoadjuvant therapy may reduce distant disease recurrence. Adjuvant treatment with OXA for rectal cancer has been motivated by benefits demonstrated in stage III colon cancer.

Objective: To determine the feasibility, toxicity, and efficacy of preoperative OXA/5FU and RT followed by total mesorectal excision (TME) and adjuvant

PURPOSE: This phase II trial is studying the side effects and how well giving neo-adjuvant combination chemotherapy with radiation works in treating patients undergoing surgery for rectal cancer.

OBJECTIVES:

Primary

• To assess the complete pathologic response rate in patients with rectal cancer treated with radiation, modified neoadjuvant FOLFOX 6 chemotherapy followed by total mesorectal excision and adjuvant modified FOLFOX 6 chemotherapy.

Secondary

• To observe the overall pathologic response rate in these patients.
• To correlate pathologic staging with preoperative ultrasound and pelvic MRI staging.
• To assess toxic side effects of these regimens in these patients.
• To assess patterns of disease relapse, disease-free survival outcomes, and overall survival outcomes of these patients.

OUTLINE:

Patients with stage II/III rectal cancer were treated with OXA 60mg/m2 weekly continuous infusion 5FU of 225 mg/m2/d d1-5 with pelvic RT of 1.8Gy/d for 28 doses. Adjuvant therapy consisted of 6 cycles of biweekly FOLFOX6.

Surgery: Patients undergo total mesorectal excision by anterior resection or an abdominal perineal resection within 4 weeks after completion of neoadjuvant therapy.

Adjuvant therapy: Within 4 weeks after surgery, patients receive modified FOLFOX 6 chemotherapy comprising oxaliplatin and leucovorin calcium IV over 2 hours on day 1 and continuous fluorouracil IV over 46 hours on days 1-2. Treatment repeats every 14 days for 6 courses in the absence of disease progression or unacceptable toxicity.

Patients complete quality of life assessment questionnaires at baseline and at each follow-up visit.

After completion of study treatment, patients are followed every 3 months for 2 years, every 6 months for 3 years, and annually thereafter.

Inclusion Criteria

• Histologically proven adenocarcinoma of the rectum with no distant metastases.
• T3-4N0M0, TanyN1-3M0 assessed by clinical exam, TRUS, MRI and CT
• The distal border of the tumor must be at or below the peritoneal reflection, defined as within 12 centimeters of the anal verge by protoscopic examination.
• No prior chemotherapy or pelvic irradiation.
• ECOG performance status 0-1
• Age 18 to 70 years
• ANC >= 1500/mm3 and platelets >= 100,000/mm3
• Serum creatinine <= 1.5 x ULN; bilirubin <= 1.5 x ULN; ALT<= 2.5 x ULN

Exclusion Criteria

• Pregnant or lactating females; patients not practicing active contraception while sexually active.
• No other serious medical condition
• A psychiatric disorder that would prohibit the subject from participating fully.
• Peripheral neuropathy > grade 1
• History within the past 5 years of a cancer diagnosis except for non-melanomatous skin cancers or in situ cervix carcinoma.
• HIV positive patients