A recent New York Magazine front page headline, "The Cancer Drug Racket," highlighted an investigative report (1) about the increasing costs of cancer drugs in America. This article describes the anger felt by Leonard Saltz, director of G.I. Oncology at Memorial Sloan-Kettering Cancer Center, when he was asked to approve an exorbitantly-priced new cancer drug, Zaltrap, very similar to several medications already on the Memorial formulary.
This article highlights what I consider to be the tip of an iceberg, the dramatically escalating cost of new cancer drugs that are quickly outstripping the ability of the nation to pay. In this new era of personalized medicine, a few of these drugs may someday markedly improve the survival of some cancer patients. However, the majority of these "promising" drugs often gain approval after "eeking" out a small, though "statistically significant" increase in survival or response in clinical trials, but at what cost? A huge price tag that is often associated with significant toxicity.
As noted by Light and Kantarjian in a commentary in the journal Cancer this month (2), 12 of the 13 new cancer drugs approved in 2013 carry an average annual price of about $100,000 while only one has demonstrated improved survival greater than two months. Because of the enormous financial benefit to the drug manufacturer, there's a premium on developing such targeted drugs. Because of the significant shift in the financial incentives as well as the attraction of being at the frontline in cancer drug development, many of my colleagues have left the practice of medicine for more lucrative positions in the pharmaceutical world. Very few medical oncologists who continue to treat cancer patients on a daily basis can afford to practice in an outpatient private practice setting. Why? Because of the lack of affordability and the financial risk to provide these medicines. In my final year in private practice, my monthly pharmaceutical costs exceeded half a million dollars. With reimbursement by insurance companies close to or below cost, as well as delays and denial of payment, it simply became financially unsustainable.
As a result of this new reality, there is the increasing consolidation of cancer therapies into large institutional settings such as hospital-based clinics and specialized cancer centers. Many medical oncologists are leaving private practice for hospital-based positions or are choosing to retire early. In this setting cancer care is BIG BUSINESS. One disturbing trend is the recent announcement of the opening of outpatient cancer treatment centers by non-medical organizations, including a large grocery chain in the Midwest! (3). Yes it's hard to believe, and let me tell you about some of the ramifications.
While there may be benefit in promoting more standardized cancer treatments, it adds to the already prohibitive cost of health care and often leads to the loss of the personal care provided by a private oncologist. Many academic oncologists work within the system and are devoted to the "latest and greatest" targeted cancer agents. They are often eager to enroll new patients, often streaming drug trial-related revenues to that institution. There is a palpable excitement when attending meetings reporting on these new agents. These new drugs in many cases reflect the most exciting breakthroughs in the molecular biology of cancer and, while some may yield significant long term benefits, their promise in many cases may go unfulfilled but their costs will be unsustainable.
In the midst of this revolution in cancer biology, there is emerging evidence suggesting improved survival rates of some cancer patients using common non-cancer medications. Two important articles, from researchers at the Harvard Medical School represent mirror images of the same critical new understanding of cancer. One article (4), "Hiding in Plain View: The Potential for Commonly Used Drugs to Reduce Breast Cancer Mortality," authored by Michelle Holmes and colleagues, is based on the relationship between the use of common non-cancer medications and improved survival of women with breast cancer noted in the Nurses Health Study (NHS) and other similar cohorts. The NHS is a long-term prospective cohort of women health professionals followed at the Harvard School of Public Health over several decades, some of whom during that period developed breast cancer and were followed with their disease. What they observed is a remarkable improvement in survival in breast cancer with the use of many common over-the-counter or generically-available prescription medications that rival or exceed in benefit the current targeted and systemic chemotherapy drugs. These include some medications recently recognized to have potential benefits in cancer (5, 6) such as the diabetic medication metformin as well as other common agents such as aspirin, non-steroidal anti-inflammatory agents, lipid lowering agents and common blood pressure medicines. Yes, aspirin!
The case for aspirin is already supported by significant evidence of reduction in colorectal cancer in those taking aspirin (9, 10). Two important papers appeared in Lancet in April 2012 (11, 12) reporting the striking findings from five large randomized cardiovascular prevention trials with many thousands of individuals from Great Britain. Participants were randomized to either daily low dose aspirin or a placebo. Those individuals on aspirin had a significant reduction in overall cancer mortality and more importantly, the largest benefit appeared to be in limiting the spread of cancer or cancer metastasis. This particular benefit produced a greater than 50 percent reduction in risk of cancer spread in the common subtypes of cancer, carcinomas such as colon, breast and lung.
My own work has focused on an antibiotic that, in Japan (13-16), in combination with conventional chemotherapy, appeared to significantly improve survival in advanced lung cancer. Despite this promising lead, it has been difficult to find interest or funding within the research community to pursue this potentially significant finding.
These studies highlight the dilemma with many widely available drugs that are difficult to study within the current system of drug research. Despite the possibility of enormous benefit for many thousands of people, the absence of significant financial incentive has delayed or prevented this critical research. These observations provide tantalizing clues that many common medicines, already widely available, have the potential to dramatically improve cancer outcomes. Until we find both the will and resources to confirm or refute these findings, many cancer patients may miss an opportunity for improved survival.
1. The Cancer Drug Racket, Hall S. New York Magazine, October 28, 2013.
2. Market spiral pricing of cancer drugs. Light DW, Kantarjian H. Cancer. 2013 Sep 3.
3. Grocery Chain to offer Chemotherapy, Other IV Treatments. Advisory.com/Daily Briefing/ 2013/ 11/ 7.
4. Hiding in plain view: the potential for commonly used drugs to reduce breast cancer mortality.
Holmes MD, Chen WY. Breast Cancer Res. 2012 Dec 10; 14 (2):216.
5. New perspective for an old antidiabetic drug: metformin as anticancer agent. Leone A, Di Gennaro E, Bruzzese F, Avallone A, Budillon A. Cancer Treat Res. 2014;159:355-76.
6. Investigating metformin for cancer prevention and treatment: the end of the beginning. Pollak MN. Cancer Discov. 2012 Sep; 2(9):778-90.
7. Statin a day keeps cancer at bay. Singh S, Singh PP. World J Clin Oncol. 2013 May 10; 4(2):43-6.
8. Therapeutic effect of β-blockers in triple-negative breast cancer postmenopausal women. Botteri E, Munzone E, Rotmensz N, Cipolla C, et al. Breast Cancer Res Treat. 2013 Aug; 140(3):567-75.
9. Aspirin use after diagnosis improves survival in older adults with colon cancer. Lai SW, Liao KF. J Am Geriatr Soc. 2013 May; 61(5):843-4.
10. Long-term effect of aspirin on colorectal cancer incidence and mortality: 20-year follow-up of five randomized trials. Rothwell PM, Wilson M, Elwin CE, Norrving B, et al. Lancet. 2010 Nov 20; 376(9754):1741-50.
11. Effect of daily aspirin on risk of cancer metastasis: a study of incident cancers during randomized controlled trials. Rothwell PM, Wilson M, Price JF, Belch JF, et al.
Lancet. 2012 Apr 28; 379(9826):1591-601.
12. Short-term effects of daily aspirin on cancer incidence, mortality, and non-vascular death: analysis of the time course of risks and benefits in 51 randomized controlled trials.
Rothwell PM, Price JF, Fowkes FG, Zanchetti A, et al. Lancet. 2012 Apr 28; 379(9826):1602-12.
13. Effect of clarithromycin on prolonging the life expectancy of patients with primary lung cancer. Mikasa K, Sawaki M, Kita E, Hamada K, et al. Jpn J Antibiot. 1997 Mar; 50 Suppl A: 45-8.
14. Significant survival benefit to patients with advanced non-small-cell lung cancer from treatment with clarithromycin. Mikasa K, Sawaki M, Kita E, Hamada K, et al. Chemotherapy. 1997 Jul-Aug; 43(4):288-96.
15. Clarithromycin is a potent inhibitor of tumor-induced angiogenesis.
Yatsunami J, Turuta N, Wakamatsu K, Hara N, Hayashi S. Res Exp Med (Berl). 1997; 197(4):189-97.
16. Clarithromycin suppresses invasiveness of human lung adenocarcinoma cells. Wada T, Sata M, Sato J, Tokairin Y, Machiya J, Hirama N, Arao T, Inoue S, Takabatake N, Shibata Y, Kubota I. Chemotherapy. 2007;53(2):77-84.