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Effect of Short-duration Preoperative Neoadjuvant Therapy With FOLFOX Based Therapy on Morbidity After Liver Resection for Colorectal Cancer Metastases

Phase 2
18 Years
Not Enrolling
Colorectal Cancer, Metastases

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Trial Information

Effect of Short-duration Preoperative Neoadjuvant Therapy With FOLFOX Based Therapy on Morbidity After Liver Resection for Colorectal Cancer Metastases

Although early stage, localized colon and rectal cancers are associated with 5 year survival
rates of nearly 90%, only a minority of patients present with localized disease.
Unfortunately, at the time of their initial presentation, approximately 35% of patients with
colon or rectal cancer have metastatic disease. Nearly two thirds of these patients with
stage IV disease have evidence of extrahepatic spread and have a median overall survival
rate of 8-10 months in the absence of further treatment. Even with the most intensive
chemotherapeutic regimens, the median overall survival for these patients ranges from 12
months to 20 months. However, a small subset of patients with stage IV disease has isolated
hepatic metastatic disease and can undergo resection. The patients with completely resected
liver metastases enjoy a significantly higher overall five-year survival, which is as high
as 58% in carefully selected patients. Ten-year overall survival has been reported in 22%
of patients. Despite this improvement, the five-year disease-free survival for these
patients is at best 35%, with hepatic recurrences occurring in 46%.

The fact that adjuvant chemotherapy improves the three-year survival rate for stage II
disease and five-year survival rates for stage III disease implies that it can treat
micrometastatic disease in some fraction of patients. Because micrometastatic disease is
likely the cause of the high recurrence rate in patients who undergo liver resection, there
is a clear biologic rationale for using postoperative adjuvant chemotherapy after liver
resection. Although this strategy is a common practice in many centers, no convincing data
that this improves survival have been reported. A large randomized phase III trial (EORTC
40983) examining this question is currently ongoing and effect on survival has not yet been
reported. Given that systemic chemotherapy after liver resection remains of unproven
benefit at the present time, many have wondered if preoperative treatment might have more
promise in improving recurrence rates.

Inclusion Criteria:

- Synchronous or metachronous colorectal metastases

- Technically resectable liver metastases

- Four or fewer metastases

- No tumors in porta hepatis

- Resection of no more than 70% of liver needed

- Medically suitable candidate for major liver resection

- FDG-PET scan without metastatic disease outside the liver

Exclusion Criteria:

- Near-obstructing or obstructing colon lesions in patients in whom combined resection
is planned (as delay for preoperative chemotherapy would be medially impossible)

- Treatment with FOLFOX or cetuximab within 12 months

- Treatment with irinotecan within 12 months

- Abnormal liver function (ALT or AST > 5x ULN, bilirubin > 3x ULN)

- Body mass index >/= 35 kg/m² (as the risk for steatohepatitis is increased)

- Renal insufficiency (Cr > 2.5mg/dL)

- Interstitial lung disease (because cetuximab has been rarely associated with
development of interstitial lung disease)

- ECOG performance score >/= 3

- Patients unable to give informed consent

- Pregnant patient (as cetuximab is a Class C drug)

- Peripheral neuropathy >/= grade II (as oxaliplatin causes neuropathy to worsen)

Type of Study:


Study Design:

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Total postoperative complication rate (Fraction of patients with any grade of complication I-V) at 30 days

Outcome Time Frame:

30 days following surgery

Safety Issue:


Principal Investigator

David Linehan, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Washington University School of Medicine


United States: Institutional Review Board

Study ID:




Start Date:

June 2007

Completion Date:

July 2011

Related Keywords:

  • Colorectal Cancer
  • Metastases
  • Colorectal Cancer
  • Metastasis
  • Neoadjuvant Therapy
  • Colorectal Neoplasms
  • Neoplasm Metastasis



Washington University School of Medicine Saint Louis, Missouri  63110