Adjuvant Chemotherapy for Older Colon Cancer Patients: From Where is the Evidence?
Abstract & Commentary
Synopsis: Colon cancer is a disease of older people with the median age being close to 70 years. Adjuvant chemotherapy is beneficial in young patients as determined by clinical trial, but these trials have included disproportionately few patients older than 65 years. In the current analysis, a database that linked NCI SEER data with Medicare claims clearly demonstrated that for the approximate 50% of those older than age 65 years with node-positive colon cancer who were treated, a survival benefit comparable to younger patients was observed. The data support the use of adjuvant 5-FU in older, node-positive colon cancer patients.
Source: Sundararajan V, et al. Ann Intern Med. 2002;136:349-357.
Systemic chemotherapy used in the adjuvant setting has been the standard of care for node-positive colon cancer for over a decade, since the publication of the Moertel reports1,2 and the NIH consensus conference.3 The final report of that phase III trial (which included levamisole with 5-FU), showed that treatment reduced the recurrence rate by 40%, the mortality rate by 33%, and did not cause detectable late side effects. Yet, in that trial, like in most large cancer treatment studies, there were a disproportionate number of young patients. It should be recalled that nearly 75% of cases of colorectal cancer are diagnosed in patients older than 65 years,4 and yet, close to 50% of such patients (node positive, older than 65 years) are treated with adjuvant therapy.5
In the current report, Sundararajan and colleagues explored a derived database from the National Cancer Institute’s Surveillance, Epidemiology, and End Results (SEER) linked with Medicare claims forms. The SEER files provided information on tumor histology and location, disease stage, individual demographic features, primary surgical and radiation treatment and survival, and the Medicare claim files provided information on diagnostic and treatment costs.
Of the 4768 Medicare covered patients older than age 65 who received a diagnosis of node-positive colon cancer from 1992-1996 in the geographically diverse sites selected by SEER for surveillance, 52% received 5-FU. For this group, the hazard ratio for death was 0.66 (95% confidence interval, 0.61-0.73). By examining Medicare claims, issues such as comorbidity or organ impairment were examined for both treated and untreated patients. Upon rigorous analysis, it was concluded that for a confounding factor to influence this result (that treated patients had improved survival), that factor would have had to have been extremely disproportionately represented in either the treatment or non treatment group. Thus, Sundararajan et al conclude that adjuvant chemotherapy for node positive elderly patients reduces death from colon cancer comparable to younger patients.
Comment by William B. Ershler, MD
The incidence of colon cancer is 6 times greater in individuals aged 65-84 than for adults younger than 65 years. Clinical trials that have demonstrated the efficacy of adjuvant chemotherapy are disproportionately biased toward younger patients, and in practice, it appears that a large segment of those eligible for treatment do not receive it, presumably because of existing comorbidity or impaired organ function. Certainly, justification for intervention in the older age group is not supported by the large clinical trials, from which they were not adequately represented.
Short of a clinical trial aimed specifically at elderly patients, the analysis provided in the current report may have to suffice. The SEER-Medicare database is a useful way to examine the effectiveness of treatment among elderly patients. Medicare covers almost all patients older than 65 years, and the claims provide useful and reliable data on treatments received for cancer, as well as comorbidities and other treatments. However, there are some deficiencies, including an acknowledged inaccuracy with regard to in-hospital- administered chemotherapy and the use of oral prescription drugs. (The study was concluded well before Capecitabine was introduced for the treatment of colon cancer). More importantly, the Medicare data do not include functional (eg, performance) status, criteria which oncologists and geriatricians agree are predictive of favorable clinical outcomes.
With these caveats in mind, the data presented are the best we have to support the use of adjuvant chemotherapy in elderly colon cancer patients. Oncologists should review the conclusions of this study carefully. Although derived from community practice and not a prospective, randomized trial, the database was large and the analysis careful enough to conclude that comparable clinical benefits should be expected in older patients. What remains to be established is the fine-tuning. In general, 5-FU-based regimens are both safe and effective. Nonetheless, there are some for whom the toxicities encountered might impair survival or significantly diminish quality of life to such an extent that the intervention would be not beneficial. Carefully-designed, community based clinical trials are likely to be our best bet in determining where to draw the line.
Dr. Ershler of INOVA Fairfax Hospital Cancer Center, Fairfax, VA; Director, Institute for Advanced Studios in Aging, Washington, D.C.
References
1. Moertel CG, et al. N Engl J Med. 1990;322:352-358.
2. Moertel CG, et al. Ann Intern Med. 1995;122:321-326.
3. NIH Consensus Conference: Adjuvant chemotherapy for patients with colon and rectal cancer. JAMA. 1990;264:1444-1450.
4. Yancik R. Cancer. 1997;80:1273-1283.
5. Sandararajan V, et al. Cancer J. 2001;7:213-218.
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