Combination Chemotherapy and Radiation Therapy in Treating Patients With Recurrent Metastatic Colorectal Cancer

OBJECTIVES:

Primary

• Determine the response rate in patients with recurrent metastatic colorectal cancer treated with neoadjuvant oxaliplatin, fluorouracil, and leucovorin calcium followed by radiotherapy and concurrent fluorouracil and oxaliplatin.

Secondary

• Determine the overall survival and disease-free survival of patients treated with this regimen.
• Determine the primary site of recurrence and time to recurrence in patients treated with this regimen.
• Determine quality of life of patients treated with this regimen.

OUTLINE: This is a nonrandomized, open-label, multicenter study.

• Neoadjuvant chemotherapy: Patients receive oxaliplatin IV over 2 hours and leucovorin calcium IV over 2 hours on day 1. Patients also receive fluorouracil IV continuously over 46 hours beginning day 1. Treatment repeats every 14 days for 4 courses in the absence of disease progression or unacceptable toxicity. Two to 5 weeks later, patients with stable or responding disease proceed to chemoradiotherapy.
• Chemoradiotherapy: Patients receive fluorouracil IV continuously 5 days a week for 5 weeks and oxaliplatin IV over 1 hour on days 1, 8, 15, 22, and 29. Patients also undergo radiotherapy 5 days a week for 5 weeks beginning on day 1.

Quality of life is assessed at baseline, 1 week after the completion of neoadjuvant chemotherapy, on days 15, 30, and 42 of chemoradiotherapy, and at 1 and 2 months after the completion of study treatment.

After completion of study treatment, patients are followed periodically.

PROJECTED ACCRUAL: A total of 39 patients will be accrued for this study.

DISEASE CHARACTERISTICS:

• Histologically confirmed adenocarcinoma of the colon or rectum

• Metastatic disease isolated to the following lymph nodes:

• Aortic
• Interaortic
• Celiomesenteric
• Retroperitoneal, including the following sites:

• Peri-uretal
• Liver
• Iliac
• Clavicle
• Mediastinum
• Inguinal
• Cervical
• Incompletely resected disease
• Recurrent disease, defined by 1 of the following criteria:

• Progression occurred within 6 months after prior oxaliplatin or after the patient received no prior oxaliplatin
• Progressive disease after cisplatin or fluorouracil
• Must be able to be encompassed in radiation field

PATIENT CHARACTERISTICS:

• ECOG performance status (PS) 0-2 or Karnofsky PS 60-100%
• Life expectancy more than 12 weeks
• Absolute neutrophil count ≥ 1,500/mm^3
• Platelet count ≥ 100,000 /mm^3
• Alkaline phosphatase ≤ 5 times normal
• Bilirubin ≤ 2 times normal
• Creatinine < 2 times normal or creatinine clearance ≥ 40 mL/min
• No peripheral neuropathy > grade 1
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No weight loss > 15% since diagnosis of recurrent disease
• No uncontrolled heart disease
• No angina
• No symptomatic disease of the inferior artery
• No psychological, familial, sociological, or geographical condition that would preclude study treatment or compliance

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics
• No prior chemotherapy or radiotherapy
• No concurrent corticosteroids