|
Advertisement |
|
|
||
 |
|
|||||
|
|||||
|
 |
||||||
|
||||||
|
||||||
|
Journal of Clinical Oncology, Vol 26, No 13 (May 1), 2008: pp. 2224-2226 © 2008 American Society of Clinical Oncology. DOI: 10.1200/JCO.2008.16.2826
Pharmacoeconomic Benefits of Capecitabine-Based Chemotherapy in Metastatic Colorectal CancerYale Cancer Center, Yale University School of Medicine, New Haven, CT
Ocala Oncology, Ocala, FL To the Editor: We are writing in response to the recent Journal of Clinical Oncology editorial by Mayer,1 comparing the costs of metastatic colorectal cancer (CRC) treatment with oxaliplatin and either capecitabine (XELOX) or infusional fluorouracil (FU) and/or leucovorin regimens, including FUOX (oxaliplatin 50 mg/m2 on day 1 and FU 1,125 mg/m2 daily of infusion on days 1 through 2 and days 8 through 9), FOLFOX-4 (oxaliplatin 85 mg/m2 on day 1, FU 400 mg/m2 daily bolus on days 1 and 2, and FU 600 mg/m2 daily infusion on days 1 and 2), and modified FOLFOX-6 (oxaliplatin 85 mg/m2 and FU 400 mg/m2 daily bolus on day 1, and FU 1,200 mg/m2 daily infusion on days 1 and 2). In this editorial, Dr Mayer notes that the criteria used to distinguish between these alternative approaches should include clinical efficacy, safety profile, patient convenience, and pharmacoeconomics. Given the equivalent clinical efficacy of the oral XELOX and infusional FU/oxaliplatin regimens as recently reported by Cassidy et al2 and Bennouna et al3 in two randomized phase III trials, the issues of adverse effect profile, patient preference, and cost take on greater importance. The cost of care is indeed an important consideration in determining a particular treatment regimen; however, drug price alone represents but one factor in the overall context of "cost of therapy." The analysis presented by Dr Mayer unfortunately misses several key factors, which, if not considered, severely undermine the validity of the analysis and its potential use as an accurate guide for helping patients with metastatic CRC, as well as physicians, to make critical decisions about treatment. Cost analyses of medical treatments require multiple elements that extend beyond the actual price of the drug and related administration procedures. Specifically, the cost of drug administration, the costs associated with managing adverse events, supportive care costs, and societal impact, which includes the indirect costs of lost productivity, must all be taken into account. Although the Mayer analysis includes the costs of drugs and the cost of drug administration, there are clear limitations in how these figures were determined. First, the cost of chemotherapy was based on the average wholesale price (AWP). In fact, AWP may not be the most accurate measure of drug cost given the wide disparity between actual selling price and the published AWP. An alternative approach would be to use wholesale acquisition cost, which would seem to be a better proxy than AWP for true drug cost, as it is the manufacturer list price offered to customers. The limitations of using AWP are highlighted in Table 1, which compares the difference in drug costs resulting from an analysis using the Center for Medicare Services (CMS) fees versus the one used in the editorial. Based on this model, the AWP for capecitabine in US dollars is nearly 500% higher than the CMS price, whereas the price for FU is quite similar, regardless of the method used. Using costs for drug administration that are identical to those in the editorial and changing only the costs of chemotherapy to those in the CMS model would show a markedly different overall cost, as seen in Table 2. Using AWP, the cost of XELOX treatment is approximately 200% higher than the FU regimens, as was noted by Dr Mayer. However, when CMS values are used, the total drug costs are only approximately 17% higher.
Dr Mayer assumes that all patients will have a central line placed. Garrison et al4 and Scheithauer et al5 state that patients receiving FOLFOX chemotherapy had about 2 to 2.5 times more central lines placed per patient than those receiving XELOX. In addition, Dr Mayer also assumes that the infusion needles and pumps would be disconnected by the patient; however, this is clearly not the case in both the academic and private practice settings. Patients typically return to the clinic to have the needle removed and return the pump into service. In the Mayer analysis, provisions are made for the infusion room charge and the pump cost. However, no mention is made of the costs of central line placement, the maintenance costs of the central line, or the costs resulting from complications associated with central venous catheters and infusional pumps. It is likely that the relatively small, (17%) difference in chemotherapy costs would be offset if these other catheter-related costs were taken into account. Recently, two different analyses of the medical resource use and costs associated with XELOX and infusional FU/oxaliplatin regimens have been reported. Garrison and colleagues compared the expected costs of XELOX and FOLFOX-4 from the United States third-party payer and societal perspectives during the study period of the randomized NO16966 phase III trial.4 In their analysis, they showed that patients receiving FOLFOX-4 required approximately 15 to 20 more office visits for drug administration than patients treated with XELOX (22 to 27 visits v 7 to 9 visits). In addition, patients receiving intravenous FOLFOX-4 spent at least 160 more hours in office and clinic visits compared with those treated with XELOX. The total direct medical costs were found to be comparable between XELOX ($44,500) and FOLFOX-4 ($45,800). Though treatment with XELOX resulted in higher drug costs, FOLFOX-4 was associated with higher drug administration costs and required about 15 more clinic visits. Moreover, the indirect costs, as determined by time and travel costs associated with treatment, were estimated to be significantly lower with XELOX chemotherapy versus FOLFOX-4, on the order of $1,500 to $1,700. However, other key societal costs (including lost wages for patients and caregivers, as well as employer costs, which would include lost worker productivity) were not factored into this analysis, which might then underestimate the overall indirect costs of treatment.
A cost-minimization analysis was conducted by Perrocheau et al6 based on the phase III randomized trial that compared XELOX with FOLFOX-6. The investigators of this study found the average cost of chemotherapy per cycle per patient to be significantly lower with XELOX when compared with FOLFOX-6 ( Finally, a retrospective database analysis was recently performed by Chu et al,7 which was based on MarketScan databases and included a large, national sample of patients with metastatic CRC who received XELOX and FOLFOX chemotherapy. For each month of treatment, this analysis determined that the XELOX regimen was associated with higher acquisition costs when compared with FOLFOX ($6,800 v $5,837). However, the higher XELOX drug cost was canceled out by the increased cost of other medications that patients receiving FOLFOX required (ie, antiemetics, growth factors, and antibiotics). When estimating the total monthly health care costs, there was a substantial savings ($2,700 per month) associated with XELOX compared with FOLFOX chemotherapy ($11,955 v $14,655). Taken together, the findings of these prospective pharmacoeconomic and cost analyses, along with the retrospective claims database analysis provide a consistent view that capecitabine-based therapy is associated with a favorable cost comparison over infusional FU-based therapy in patients with CRC. These analyses certainly provide a significantly different conclusion than that argued in the Mayer editorial. Dr Mayer is to be commended for opening the dialogue on the critical role of pharmacoeconomics in the treatment decision-making process. However, it is clear that a more comprehensive analysis of healthcare costs beyond simply estimating drug costs, infusion room charges, and pump cost is required before any meaningful conclusions can be drawn as to the real pharmacoeconomic advantages of one regimen over another. Although additional work is required to determine total societal costs of XELOX compared with FOLFOX chemotherapy, there is indeed strong supportive evidence that substitution of capecitabine for infusional FU, whether it be FOLFOX-4 or FOLFOX-6, results in a more convenient regimen, reduces the number and duration of infusion visits, and reduces overall patient costs. Given the available data for clinical equivalence of XELOX and FOLFOX chemotherapy, the safety profile equivalence, the clear patient preference for oral capecitabine versus intravenous FU chemotherapy, and the more detailed cost analyses showing at least cost equivalence, if not superiority, we believe that the case can now be made for the substitution of capecitabine for infusional FU as the backbone for oxaliplatin-based combinations. AUTHORS’ DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST Although all authors completed the disclosure declaration, the following author(s) indicated a financial or other interest that is relevant to the subject matter under consideration in this article. Certain relationships marked with a "U" are those for which no compensation was received; those relationships marked with a "C" were compensated. For a detailed description of the disclosure categories, or for more information about ASCO's conflict of interest policy, please refer to the Author Disclosure Declaration and the Disclosures of Potential Conflicts of Interest section in Information for Contributors. Employment or Leadership Position: None Consultant or Advisory Role: Edward Chu, Roche (C); Thomas H. Cartwright, Roche (C) Stock Ownership: None Honoraria: Edward Chu, Roche; Thomas H. Cartwright, Roche Research Funding: None Expert Testimony: None Other Remuneration: None
REFERENCES
1. Mayer RJ: Should capecitabine replace infusional fluorouracil and leucovorin when combined with oxaliplatin in metastatic colorectal cancer? J Clin Oncol 25:4165-4167, 2007 2. Cassidy J, Clarke S, Diaz-Rubio E, et al: XELOX vs. FOLFOX4: Efficacy results from XELOX-1/NO16966, a randomized phase II trial in first-line metastatic colorectal cancer (MCRC). J Clin Oncol 25:171s, 2007 (suppl; abstr 4030)[CrossRef] 3. Ducreux M, Bennouna J, Hebbar M, et al: Efficacy and safety findings from a randomized phase II study of capecitabine (X) + oxaliplatin (O) (XELOX) vs. infusional 5-FU/LV + O (FOLFOX-6) for metastatic colorectal cancer (MCRC). J Clin Oncol 25:170s, 2007 (suppl; abstr 4029) 4. Garrison L, Cassidy J, Saleh M, et al: Cost comparison of XELOX compared to FOLFOX-4 with or without bevacizumab (bev) in metastatic colorectal cancer. J Clin Oncol 25:182s, 2007 (suppl; abstr 4074) 5. Scheithauer W, Cassidy J, Figer A, et al: A comparison of medical resource use for 4 chemotherapy regimens as first-line treatment for metastatic colorectal cancer (MCRC): XELOX vs. FOLFOX-4 bevacizumab (A). J Clin Oncol 25:188s, 2007 (suppl; abstr 4098) 6. Perrocheau G, Bennouna J, Ducreux M, et al: Cost-minimization analysis of a phase III study of capecitabine + oxaliplatin (XELOX) vs. infusional 5-FU/LV + oxaliplatin (FOLFOX-6) as first-line treatment for metastatic colorectal cancer (MCRC) in the French setting. J Clin Oncol 25:184s, 2007 (suppl; abstr 4083) 7. Chu E, Zelt S, Song X: A claims database cost-comparison analysis of capecitabine in the treatment of patients with colon or rectal cancer (CRC). Gastrointestinal Cancer Symposium, January 26-28, 2008 (abstr 364) Related Reply
Related Article
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|
|||||||||||
|
|||||||||||
|
|
Copyright © 2008 by the American Society of Clinical Oncology, Online ISSN: 1527-7755. Print ISSN: 0732-183X
|
608 ± 446 v 
