Combination Chemotherapy in Treating Patients With Unresectable Metastatic Colorectal Cancer

Summary

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 may kill more tumor cells. It is not yet known which regimen of combination chemotherapy is more effective for advanced colorectal cancer. PURPOSE: Randomized phase III trial to compare the effectiveness of fluorouracil combined with leucovorin and either irinotecan or oxaliplatin in treating patients who have unresectable metastatic colorectal cancer.

Timeline

Start

2000-05

Primary completion

—

Completion

2003-12

Outcome

Met primary endpoint

paper However, log-rank comparison of each group against control showed that only C-ir--the first-line combination strategy including irinotecan--satisfied the statistical test for superiority (p=0.01). PMID 17630037 ↗

Publications

• Background Richman SD, Chambers P, Seymour MT, Daly C, Grant S, Hemmings G, Quirke P. Intra-tumoral heterogeneity of KRAS and BRAF mutation status in patients with advanced colorectal cancer (aCRC) and cost-effectiveness of multiple sample testing. Anal Cell Pathol (Amst). 2011;34(1-2):61-6. doi: 10.3233/ACP-2011-0005.
• Results Braun MS, Richman SD, Thompson L, Daly CL, Meade AM, Adlard JW, Allan JM, Parmar MK, Quirke P, Seymour MT. Association of molecular markers with toxicity outcomes in a randomized trial of chemotherapy for advanced colorectal cancer: the FOCUS trial. J Clin Oncol. 2009 Nov 20;27(33):5519-28. doi: 10.1200/JCO.2008.21.6283. Epub 2009 Oct 26.
• Results Richman SD, Seymour MT, Chambers P, Elliott F, Daly CL, Meade AM, Taylor G, Barrett JH, Quirke P. KRAS and BRAF mutations in advanced colorectal cancer are associated with poor prognosis but do not preclude benefit from oxaliplatin or irinotecan: results from the MRC FOCUS trial. J Clin Oncol. 2009 Dec 10;27(35):5931-7. doi: 10.1200/JCO.2009.22.4295. Epub 2009 Nov 2.
• Results Seymour MT, Maughan TS, Ledermann JA, Topham C, James R, Gwyther SJ, Smith DB, Shepherd S, Maraveyas A, Ferry DR, Meade AM, Thompson L, Griffiths GO, Parmar MK, Stephens RJ; FOCUS Trial Investigators; National Cancer Research Institute Colorectal Clinical Studies Group. Different strategies of sequential and combination chemotherapy for patients with poor prognosis advanced colorectal cancer (MRC FOCUS): a randomised controlled trial. Lancet. 2007 Jul 14;370(9582):143-152. doi: 10.1016/S0140-6736(07)61087-3.
• Results Maughan T: Fluorouracil (FU), oxaliplatin (OX), CPT-11 (irinotecan, Ir), use and sequencing, in advanced colorectal cancer (ACRC): the UK MRC FOCUS (CR08) trial. [Abstract] American Society of Clinical Oncology 2005 Gastrointestinal Cancers Symposium, 27-29 January 2005, Miami, Florida. A-165, 2005.
• Results Seymour MT: Fluorouracil, oxaliplatin and CPT-11 (irinotecan), use and sequencing (MRC FOCUS): a 2135-patient randomized trial in advanced colorectal cancer (ACRC). [Abstract] J Clin Oncol 23 (Suppl 16): A-3518, 250s, 2005.
• Results Seymour M: An update on the MRC FOCUS/CR08 trial: the first 300 patients. [Abstract] Br J Cancer 85 (suppl 1): A-P45, 44, 2001.

Drugs

Indications