Neo-adjuvant Chemoradiation With Oxaliplatin/5-FU in 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