Capecitabine and Oxaliplatin or Standard Follow-Up Care in Treating Patients Who Have Undergone Surgery for Locally Advanced Rectal Cancer

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. Giving combination chemotherapy after surgery may kill any tumor cells that remain after surgery. It is not yet known whether giving capecitabine together with oxaliplatin is more effective than standard follow-up care in treating rectal cancer that was removed by surgery.

PURPOSE: This randomized phase III trial is studying capecitabine and oxaliplatin to see how well they work compared with standard follow-up care in treating patients who have undergone surgery for locally advanced rectal cancer.

OBJECTIVES:

* Compare the efficacy of adjuvant chemotherapy comprising capecitabine and oxaliplatin vs standard follow-up care, in terms of disease-free and overall survival, in patients with clear margins after complete resection of locally advanced rectal cancer.

OUTLINE: This is an open-label, randomized, controlled, prospective, multicenter study. Patients are stratified according to surgeon and nodal status (node positive vs node negative vs unknown). Patients are randomized to 1 of 2 treatment arms.

* Arm I: Patients undergo standard follow up.
* Arm II: Patients receive oral capecitabine twice daily on days 1-14 and oxaliplatin IV over 2 hours on day 1. Treatment repeats every 3 weeks for up to 6 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed every 3 months for 2 years, every 6 months for 5 years, and then annually thereafter.

Peer Reviewed and Funded or Endorsed by Cancer Research UK

PROJECTED ACCRUAL: A total of 800 patients will be accrued for this study.

Eligibility Criteria:
DISEASE CHARACTERISTICS:

* Histologically confirmed adenocarcinoma of the rectum

  * Within 15 cm of the anal verge
  * Locally advanced disease
* Underwent complete resection of primary tumor within the past 12 weeks

  * ypT0-4, N0-2 with definitive histology at surgery
  * Circumferential resection margin \> 1 mm
  * No gross evidence of residual disease
* Received neoadjuvant fluoropyrimidine-based chemoradiotherapy with ≥ 45 Gy planned total radiation dose, given in 1 of the following fashions:

  * Prolonged fluorouracil IV during radiotherapy
  * Low-dose leucovorin calcium and fluorouracil (days 1-5 and 29-33) concurrently with radiotherapy
  * Oral capecitabine concurrently with radiotherapy
* No evidence of metastatic disease

PATIENT CHARACTERISTICS:

* WHO performance status 0-1
* Absolute neutrophil count ≥ 1,500/mm³
* Platelet count ≥ 100,000/mm³
* Creatinine clearance ≥ 50 mL/min
* Bilirubin ≤ 1.25 times upper limit of normal (ULN)
* AST and ALT ≤ 1.25 times ULN
* Not pregnant or nursing
* Negative pregnancy test
* Fertile patients must use effective contraception during and for ≥ 3 months after completion of study treatment
* No known dihydropyrimidine dehydrogenase deficiency
* No hypersensitivity to platinum compounds
* No preexisting peripheral neuropathy ≥ grade 1
* No lack of physical integrity of the upper gastrointestinal tract
* No malabsorption syndrome
* No other serious uncontrolled medical condition or concurrent medical illness that would compromise life expectancy and/or preclude study compliance, including any of the following:

  * Serious uncontrolled infections
  * Significant cardiac disease (e.g., uncontrolled angina, congestive heart failure, cardiomyopathy, or arrhythmias) or myocardial infarction within the past 12 months
  * Interstitial pneumonia or symptomatic lung fibrosis
* No other malignancies except adequately treated in situ carcinoma of the cervix or basal cell or squamous cell carcinoma of the skin, unless disease-free for ≥ 10 years
* No history of uncontrolled seizures, CNS disorders, or psychiatric disability that would preclude study compliance

PRIOR CONCURRENT THERAPY:

* See Disease Characteristics
* No prior chemotherapy exceeding 6 weeks in duration

  * Prior chemotherapy given as part of neoadjuvant treatment (i.e., chemoradiotherapy) may last a maximum of 11-12 weeks
* No prior oxaliplatin
* Prior mitomycin C, irinotecan hydrochloride, or cetuximab allowed
* No concurrent warfarin, antiviral agents, or phenytoin