Colon Cancer Treatment (PDQ®): Treatment - Health Professional Information [NCI] - Stage IV and Recurrent Colon Cancer Treatment
When 5-FU was the only active chemotherapy drug, trials in patients with locally advanced, unresectable, or metastatic disease demonstrated partial responses and prolongation of the time-to-progression (TTP) of disease [41,42] as well as improved survival and quality of life for patients receiving chemotherapy, compared with the best supportive care.[43,44,45] Several trials have analyzed the activity and toxic effects of various 5-FU-leucovorin regimens using different doses and administration schedules and showed essentially equivalent results with a median survival time in the 12-month range.
Prior to the advent of multiagent chemotherapy, two randomized studies demonstrated that capecitabine was associated with equivalent efficacy when compared with the Mayo Clinic regimen of 5-FU-leucovorin.[47,48][Level of evidence: 1iiA]
Three randomized studies demonstrated improved response rates, PFS, and OS when irinotecan or oxaliplatin was combined with 5-FU-leucovorin.[49,50,51]
- An intergroup study (NCCTG-N9741) compared IFL with FOLFOX4 in first-line treatment for patients with metastatic colorectal cancer.
- Patients assigned to FOLFOX4 experienced an improved PFS (median, 6.9 months vs. 8.7 months; P = .014; hazard ratio [HR], 0.74; 95% confidence interval [CI], 0.61–0.89) and OS (15.0 months vs. 19.5 months, P = .001; HR, 0.66; 95% CI, 0.54–0.82) compared with patients randomly assigned to IFL.[Level of evidence: 1iiA]
- Subsequently, two studies compared FOLFOX with FOLFIRI, and patients were allowed to cross over upon progression on first-line therapy, respectively.[52,53][Level of evidence: 1iiDiii]
- PFS and OS were identical between the treatment arms in both studies.
- The Bolus, Infusional, or Capecitabine with Camptosar-Celecoxib (BICC-C) trial evaluated several different irinotecan-based regimens in patients with previously untreated metastatic colorectal cancer, including FOLFIRI, mIFL, and Capecitabine/irinotecan (CAPIRI).[Level of evidence: 1iiA]
- The study randomly assigned 430 patients and was closed early due to poor accrual.
- The patients who received FOLFIRI had a better PFS than the patients who received either mIFL (7.6 months vs. 5.9 months, P = .004) or CAPIRI (7.6 months vs. 5.8 months, P = .015).
- Patients who received CAPIRI had the highest grade 3 or higher rates of nausea, vomiting, diarrhea, dehydration, and hand-foot syndrome.
Since the publication of these studies, the use of either FOLFOX or FOLFIRI is considered acceptable for first-line treatment of patients with metastatic colorectal cancer.
When using an irinotecan-based regimen as first-line treatment of metastatic colorectal cancer, FOLFIRI is preferred.[Level of evidence: 1iiDiii]
Randomized phase III trials have addressed the equivalence of substituting capecitabine for infusional 5-FU. Two phase III studies have evaluated FUOX versus CAPOX.[55,56]
- The AIO Colorectal Study Group randomly assigned 474 patients to either FUFOX or CAPOX.
- The median PFS was 7.1 months for the CAPOX arm and 8.0 months for the FUFOX arm (HR, 1.17; 95% CI, 0.96–1.43, P = .117), and the HR was in the prespecified equivalence range.
- The Spanish Cooperative Group randomly assigned 348 patients to CAPOX or FUOX.
- The TTP was 8.9 months versus 9.5 months (P = .153) and met the prespecified range for noninferiority.[Level of evidence: 1iiDiii]