Find Information About:

Drugs & Supplements

Get information and reviews on prescription drugs, over-the-counter medications, vitamins, and supplements. Search by name or medical condition.

Pill Identifier

Pill Identifier

Having trouble identifying your pills?

Enter the shape, color, or imprint of your prescription or OTC drug. Our pill identification tool will display pictures that you can compare to your pill.

Get Started
My Medicine

My Medicine

Save your medicine, check interactions, sign up for FDA alerts, create family profiles and more.

Get Started

WebMD Health Experts and Community

Talk to health experts and other people like you in WebMD's Communities. It's a safe forum where you can create or participate in support groups and discussions about health topics that interest you.

  • Second Opinion

    Second Opinion

    Read expert perspectives on popular health topics.

  • Community


    Connect with people like you, and get expert guidance on living a healthy life.

Got a health question? Get answers provided by leading organizations, doctors, and experts.

Get Answers

Sign up to receive WebMD's award-winning content delivered to your inbox.

Sign Up

Colorectal Cancer Health Center

Font Size

Colon Cancer Treatment (PDQ®): Treatment - Health Professional Information [NCI] - Stage IV and Recurrent Colon Cancer Treatment


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.[58][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.[59,60]

Evidence (oxaliplatin):

  1. 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.
  2. The Spanish Cooperative Group randomly assigned 348 patients to CAPOX or FUOX.[59]
    • The TTP was 8.9 months versus 9.5 months (P = .153) and met the prespecified range for noninferiority.[59][Level of evidence: 1iiDiii]

When using an oxaliplatin-based regimen as first-line treatment of metastatic colorectal cancer, a CAPOX regimen is not inferior to a FUOX regimen.

Before the availability of cetuximab, panitumumab, bevacizumab, and aflibercept as second-line therapy, second-line chemotherapy with irinotecan in patients treated with 5-FU/LV as first-line therapy demonstrated improved OS when compared with either infusional 5-FU or supportive care.[61,62,63,64]

Similarly, a phase III trial randomly assigned patients who progressed on irinotecan and 5-FU/LV to bolus and infusional 5-FU/LV (LV5FU2), single-agent oxaliplatin, or FOLFOX4. The median TTP for FOLFOX4 versus LV5FU2 was 4.6 months versus 2.7 months (stratified log-rank test, 2-sided P < .001).[65][Level of evidence: 1iiDiii]


Bevacizumab is a partially humanized monoclonal antibody that binds to vascular endothelial growth factor. Bevacizumab can reasonably be added to either FOLFIRI or FOLFOX for patients undergoing first-line treatment of metastatic colorectal cancer.

Evidence (bevacizumab):

  1. After bevacizumab was approved, the BICC-C trial was amended, and an additional 117 patients were randomly assigned to receive FOLFIRI/bevacizumab or mIFL/bevacizumab.
    • Although the primary endpoint, PFS, was not significantly different, patients receiving FOLFIRI/bevacizumab had a significantly better OS (not yet reached with a median follow-up of 22.6 months vs. 19.2 months, P = .007).
  2. Patients with previously untreated metastatic colorectal cancer were randomly assigned to either IFL or IFL and bevacizumab.[66]
    • The patients randomly assigned to IFL and bevacizumab experienced a significantly better PFS (10.6 months in the group given IFL and bevacizumab, as compared with 6.2 months in the group given IFL and placebo; HR for disease progression, 0.54; P < .001) and OS (20.3 months in the group given IFL and bevacizumab, as compared with 15.6 months in the group given IFL and placebo corresponding to an HR for death, 0.66; P < .001).[66][Level of evidence: 1iiA]
  3. Despite the lack of direct data, in standard practice, bevacizumab was added to FOLFOX as a standard first-line regimen based on the results of the NCCTG-N9741 trial.[67] Subsequently, in a randomized phase III study, patients with untreated stage IV colorectal cancer were randomly assigned in a 2 × 2 factorial design to CAPOX versus FOLFOX4, then to bevacizumab versus placebo. PFS was the primary endpoint.
    • In this trial, 1,401 patients were randomly assigned, and the median PFS was 9.4 months for patients receiving bevacizumab and 8.0 months for the patients receiving placebo (HR, 0.83; 97.5% CI, 0.72-0.95, P = .0023).[68][Level of evidence: 1iiDiii]
    • Median OS was 21.3 months for patients receiving bevacizumab and 19.9 months for patients receiving placebo (HR, 0.89; 97.5% CI, 0.76-1.03, P = .077).
    • The median PFS (intention-to-treat analysis) was 8.0 months in the pooled CAPOX-containing arms versus 8.5 months in the FOLFOX4-containing arms (HR, 1.04; 97.5% CI, 0.93-1.16), with the upper limit of the 97.5% CI being below the predefined noninferiority margin of 1.23.[68,69]
    • The effect of bevacizumab on OS is likely to be less than what was seen in the original Hurwitz study.[66]
  4. Investigators from the Eastern Cooperative Oncology Group randomly assigned patients who had progressed on 5-FU-leucovorin and irinotecan to either FOLFOX or FOLFOX and bevacizumab.
    • Patients randomly assigned to FOLFOX and bevacizumab experienced a statistically significant improvement in PFS (7.43 months vs. 4.7 months, HR, 0.61; P < .0001) and OS (12.9 months vs. 10.8 months, HR, 0.75; P = .0011).[70][Level of evidence: 1iiA]
1 | 2 | 3 | 4 | 5 | 6 | 7 | 8 | 9 | 10
1 | 2 | 3 | 4 | 5 | 6 | 7 | 8 | 9 | 10
Next Article:

Today on WebMD

Colorectal cancer cells
The right diagnosis is the most important factor.
man with a doctor
Our health check will steer you in the right direction.
sauteed cherry tomatoes
Fight cancer one plate at a time.
bladder cancer x-ray
Do you know the warning signs?
Colon vs Rectal Cancer
New Colorectal Treatments
can lack of sleep affect your immune system
Cancer Facts Quiz
Virtual Colonoscopy
Picture of the Colon
Vitamin D