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Monday, July 26, 2004

WHAT PRICE PALLIATION????
This editorial appeared in last week's New England Journal of Medicine
The Price Tag on Progress — Chemotherapy for Colorectal Cancer. The moderator of the weekly cancer conference at Big Hospital gave a little talk about it today. It seems that we are paying a lot for a little time:
Better systemic therapy has considerably improved prognosis. Without chemotherapy, the median duration of survival among patients with metastatic colorectal cancer was eight months. With fluorouracil, it increased to 12 months. After 2002, the availability of three cytotoxic agents (fluorouracil, irinotecan, and oxaliplatin) further extended the median survival to 21 months. Although clinical-trial data are not yet mature, bevacizumab and cetuximab are likely to prolong median survival beyond 21 months. But despite the panoply of options, treatment remains palliative, and there is not yet evidence that the new therapies increase cure rates.


In the wake of the optimism generated by recent trial results, patients experience sticker shock when they encounter the prices of chemotherapy drugs. Physicians find themselves in the undesirable position of having to help patients make decisions about whether the potential clinical benefits warrant the financial strain that even the copayments for these medications may create. Consider the drug costs for a patient with colorectal cancer who is 170 cm tall, weighs 70 kg, and receives chemotherapy for eight weeks — the duration typically required to determine response. The Mayo Clinic regimen (fluorouracil and leucovorin) costs $63. The FOLFOX regimen (fluorouracil, leucovorin, and oxaliplatin) costs $11,889, and FOLFOX combined with bevacizumab costs $21,033 (see Table). The near-doubling of the median survival achieved over the past decade has been accompanied by a staggering 340-fold increase in drug costs — just for the initial eight weeks of treatment.
So for a regimen that is not even curative, the costs of the drugs rises rapidly.  The next paragraph brings it into more perspective:
The combination of irinotecan and cetuximab for second- and third-line treatment of metastatic colorectal cancer, as described by Cunningham et al. in this issue of the Journal (pages 337–345), increases the median survival by 1.7 months. In the United States, the regimen costs approximately $30,790 for an eight-week course. Assuming that an average patient continues to receive treatment until the median time to progression, 8 months of front-line therapy followed by 4.1 months of irinotecan–cetuximab therapy would cost $161,000. In 2004, 32,000 people in the United States will receive a diagnosis of stage IV colorectal cancer, and recurrent metastatic disease will develop in an additional 24,000. The drug costs for an eight-week course of initial treatment for these 56,000 patients will be approximately $666 million — or $1.2 billion with the addition of monoclonal-antibody therapy. These cost estimates are exclusively for drugs; they do not include the costs of preparation, administration and supervision, or supportive medications. They presume that every single milligram of drug is effectively utilized. Yet cetuximab, for example, is manufactured only in a 100-mg vial, and because the medication cannot be stored for long periods, leftovers go to waste, particularly in small practice environments.
Other items not included are hospitalizations due to chemotherapy complications or other medications, such as anti-emetics, that are used as well. How many screening colonoscopies could that kind of money pay for? Not only can the 1.7 months of increased survival be expensive, but what sort of quality can one have? Some may be well enough to take a trip or see a family member's graduation or wedding, all priceless events, but many others will spend that time nauseated, weak, and anemic. To throw another wrench in the works, monoclonal antibodies are now being used in the treatment of advanced lung cancer, a disease that affects close to three times the number of patients that advanced colorectal cancer does.
Then my evil, cynical side came out. Dr. Smith has already sung the praises of the NEJM for raising this issue and calls for future examinations of cost/benefit ratios.  What would have happened if an editorial asking the same questions about a politically-sensitive disease such as breast cancer or HIV/AIDS had been published?  Would it have been published?  The hue and cry would have been impressive to say the least. Lastly:
As a society, we are reluctant to systematically deny access to expensive treatments that extend life by only a few weeks, but the morality of refusing to make deliberated choices is itself questionable.
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