Surgery With or Without Combination Chemotherapy in Treating Patients With Liver Metastases From Colorectal Cancer

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug and combining chemotherapy with surgery may kill more tumor cells. It is not yet known if surgery is more effective with or without chemotherapy for liver metastases. PURPOSE: Randomized phase III trial to compare the effectiveness of surgery with or without combination chemotherapy in treating patients who have liver metastases from colorectal cancer.

Sex

All

Minimum age

18 Years

Maximum age

80 Years

DISEASE CHARACTERISTICS:

* Diagnosis of potentially resectable colorectal liver metastases that meets one of the following criteria:

  * Metachronous metastases after complete resection of primary tumor without gross or microscopic evidence of residual disease
  * Synchronous metastases after complete resection of primary tumor more than 1 month before study
  * Synchronous metastases with sufficient evidence (i.e., CAT scan or diagnostic laparoscopy) that both the primary tumor and liver metastases can be completely resected during the same procedure and resection of primary may be delayed 3-4 months

PATIENT CHARACTERISTICS:

Age:

* 18 to 80

Performance status:

* WHO 0-2
* Karnofsky 60-100%

Life expectancy:

* Not specified

Hematopoietic:

* Absolute neutrophil count greater than 1,500/mm\^3
* Platelet count greater than 100,000/mm\^3

Hepatic:

* No hepatic insufficiency

Renal:

* Creatinine less than 2 times upper limit of normal

Cardiovascular:

* No uncontrolled congestive heart failure or angina pectoris
* No hypertension or arrhythmia

Other:

* No other malignancy within the past 10 years except adequately treated carcinoma in situ of the cervix or nonmelanoma skin cancer
* No peripheral neuropathy greater than grade 1
* No prior significant neurologic or psychiatric disorders
* No active infection
* Not pregnant or nursing
* Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy:

* No concurrent biologic therapy

Chemotherapy:

* No prior chemotherapy for advanced disease
* Prior adjuvant chemotherapy for primary cancer allowed unless included oxaliplatin
* No other concurrent chemotherapy

Endocrine therapy:

* No concurrent anticancer endocrine therapy

Radiotherapy:

* No concurrent radiotherapy

Surgery:

* See Disease Characteristics

Other:

* At least 30 days since prior investigational drugs
* No concurrent investigational drugs

• RESULTSorbye H, Mauer M, Gruenberger T, et al.: Predictive factors for the effect of perioperative FOLFOX for resectable liver metastasis in colorectal cancer patients (EORTC phase III study 40983). [Abstract] J Clin Oncol 28 (Suppl 15): A-3544, 2010.
• RESULTSorbye H, Mauer M, Gruenberger T, et al.: Evaluation of carcinoembryonic antigen (CEA) as a predictive baseline factor for the benefit of perioperative FOLFOX in resectable liver metastasis from colorectal cancer (EORTC study 40983). [Abstract] American Society of Clinical Oncology 2010 Gastrointestinal Cancers Symposium, 22-24 January 2010, Orlando, Florida. A-407, 2010.
• RESULTBenoist S, Nordlinger B. The role of preoperative chemotherapy in patients with resectable colorectal liver metastases. Ann Surg Oncol. 2009 Sep;16(9):2385-90. doi: 10.1245/s10434-009-0492-7. Epub 2009 Jun 25. PMID 19554377
• RESULTNordlinger B, Sorbye H, Glimelius B, Poston GJ, Schlag PM, Rougier P, Bechstein WO, Primrose JN, Walpole ET, Finch-Jones M, Jaeck D, Mirza D, Parks RW, Collette L, Praet M, Bethe U, Van Cutsem E, Scheithauer W, Gruenberger T; EORTC Gastro-Intestinal Tract Cancer Group; Cancer Research UK; Arbeitsgruppe Lebermetastasen und-tumoren in der Chirurgischen Arbeitsgemeinschaft Onkologie (ALM-CAO); Australasian Gastro-Intestinal Trials Group (AGITG); Federation Francophone de Cancerologie Digestive (FFCD). Perioperative chemotherapy with FOLFOX4 and surgery versus surgery alone for resectable liver metastases from colorectal cancer (EORTC Intergroup trial 40983): a randomised controlled trial. Lancet. 2008 Mar 22;371(9617):1007-16. doi: 10.1016/S0140-6736(08)60455-9. PMID 18358928
• RESULTJulie C, Lutz MP, Aust D, et al.: Pathological analysis of hepatic injury after oxaliplatin-based neoadjuvant chemotherapy of colorectal cancer liver metastases: results of the EORTC Intergroup phase III study 40983. [Abstract] American Society of Clinical Oncology 2007 Gastrointestinal Cancers Symposium, 19 -21 January 2007, Orlando, Florida A-241, 2007.
• RESULTNordlinger B, Sorbye H, Collette L, et al.: Final results of the EORTC Intergroup randomized phase III study 40983 [EPOC] evaluating the benefit of peri-operative FOLFOX4 chemotherapy for patients with potentially resectable colorectal cancer liver metastases. [Abstract] J Clin Oncol 25 (Suppl 18): A-LBA5, 2007.