Open Access Highly Accessed Open Badges Research article

Unsupported off-label chemotherapy in metastatic colon cancer

Jonas A de Souza12*, Blase Polite123, Monica Perkins4, Neal J Meropol5, Mark J Ratain126, Lee N Newcomer4 and G Caleb Alexander7

Author Affiliations

1 Section of Hematology/Oncology, The University of Chicago Medicine, Chicago, IL, USA

2 Comprehensive Cancer Center, The University of Chicago Medicine, Chicago, IL, USA

3 Center for Interdisciplinary Health Disparities Research, The University of Chicago Medicine, 5841 South Maryland Avenue, MC 2115, Chicago, IL, 60637-1470, USA

4 UnitedHealthcare, Edina, Minnesota, USA

5 Division of Hematology and Oncology, University Hospitals Case Medical Center Seidman Cancer Center, Case Western Reserve University, Case Comprehensive Cancer Center, Cleveland, Ohio, USA

6 Committee on Clinical Pharmacology and Pharmacogenomics and Center for Personalized Therapeutics, The University of Chicago, Chicago, IL, USA

7 Section of General Medicine and Center for Health and the Social Sciences, University of Chicago, Chicago, IL, USA

For all author emails, please log on.

BMC Health Services Research 2012, 12:481  doi:10.1186/1472-6963-12-481

Published: 29 December 2012



Newer systemic therapies have the potential to decrease morbidity and mortality from metastatic colorectal cancer, yet such therapies are costly and have side effects. Little is known about their non-evidence-based use.


We conducted a retrospective cohort study using commercial insurance claims from UnitedHealthcare, and identified incident cases of metastatic colon cancer (mCC) from July 2007 through April 2010. We evaluated the use of three regimens with recommendations against their use in the National Comprehensive Cancer Center Network Guidelines, a commonly used standard of care: 1) bevacizumab beyond progression; 2) single agent capecitabine as a salvage therapy after failure on a fluoropyridimidine-containing regimen; 3) panitumumab or cetuximab after progression on a prior epidermal growth factor receptor antibody. We performed sensitivity analyses of key assumptions regarding cohort selection. Costs from a payer perspective were estimated using the average sales price for the entire duration and based on the number of claims.


A total of 7642 patients with incident colon cancer were identified, of which 1041 (14%) had mCC. Of those, 139 (13%) potentially received at least one of the three unsupported off-label (UOL) therapies; capecitabine was administered to 121 patients and 49 (40%) likely received it outside of clinical guidelines, at an estimated cost of $718,000 for 218 claims. Thirty-eight patients received panitumumab and six patients (16%) received it after being on cetuximab at least two months, at an estimated cost of $69,500 for 19 claims. Bevacizumab was administered to 884 patients. Of those, 90 (10%) patients received it outside of clinical guidelines, at an estimated costs of $1.34 million for 636 claims.


In a large privately insured mCC cohort, a substantial number of patients potentially received UOL treatment. The economic costs and treatment toxicities of these therapies warrant increased efforts to stem their use in settings lacking sufficient scientific evidence.

Colorectal cancer; Off-label; Evidence-based medicine; Physician practice patterns