A Phase II Study of Capecitabine, Oxaliplatin and Selenomethionine and Radiation Therapy in Patients With Stage II and III Rectal Adenocarcinoma
A Phase II Study of Capecitabine, Oxaliplatin and Selenomethionine and Radiation Therapy in Patients With Stage II and III Rectal Adenocarcinoma
RATIONALE: Drugs used in chemotherapy, such as capecitabine and oxaliplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Selenomethionine may slow the growth of tumor cells. Radiation therapy uses high-energy x-rays to kill tumor cells. Giving combination chemotherapy together With selenomethionine and radiation therapy may kill more tumor cells.
PURPOSE: This phase II trial is studying how well selenomethionine works when given together with capecitabine, oxaliplatin, and radiation therapy in treating patients undergoing surgery for newly diagnosed stage II or stage III rectal cancer.
OBJECTIVES:
Primary
Secondary
OUTLINE: Patients receive neoadjuvant therapy comprising oral selenomethionine twice daily for 1 week prior to radiotherapy and then once daily for 6 weeks. Patients also receive oxaliplatin IV over 2 hours on days 1-7 and oral capecitabine twice daily on days 1-5 for 6 weeks and undergo radiotherapy 5 days a week for 6 weeks. Treatment continues in the absence of disease progression or unacceptable toxicity.
Within 4-8 weeks after completion of neoadjuvant therapy, patients undergo curative-intent surgery. Beginning 4-8 weeks after surgery, patients may receive up to 9 courses of standard adjuvant combination chemotherapy (FOLFOX).
Blood samples are collected at baseline and weekly during treatment and analyzed by absorption spectrophotometry for selenium measurement of drug concentration. Pharmacokinetic studies are also performed.
After completion of study treatment, patients are followed for up to 5 years.
DISEASE CHARACTERISTICS:
Histologically confirmed rectal adenocarcinoma that is involving the distal 12 cm of the rectum (above the anal verge)
No evidence of distant or known metastases
PATIENT CHARACTERISTICS:
ECOG performance status (PS) 0-1 OR Karnofsky PS 70-100%
Life expectancy > 1 year
Leukocytes ≥ 3,000/µL
Absolute neutrophil count ≥ 1,500/µL
Platelet count ≥ 100,000/µL
Total bilirubin ≤ upper limit of normal (ULN)
AST/ALT ≤ 2.5 times ULN
Creatinine ≤ ULN OR creatinine clearance ≥ 60 mL/min
Able to receive oral medication
Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception
No other concurrent or previous malignancies unless disease free for > 5 years (excluding nonmelanoma skin cancer)
No neuropathy ≥ grade 2
No history of allergic reaction attributed to compounds of similar chemical or biologic composition to oxaliplatin, capecitabine, or selenomethionine
No uncontrolled intercurrent illness including, but not limited to, any of the following:
PRIOR CONCURRENT THERAPY: