Chronic Illness and the Success of Adjuvant Colon Cancer Chemotherapy: Some Good News
Abstract & Commentary
By William B. Ershler, MD, Editor, INOVA Fairfax Hospital Cancer Center, Fairfax, VA; Director, Institute for Advanced Studies in Aging, Washington, DC.
Synopsis: The effectiveness of adjuvant chemotherapy for patients with stage III colon cancer is well established but it is less frequently prescribed in older patients. One possible explanation is a concern that existing comorbidities may reduce effectiveness of treatment. In an analysis of SEER-Medicare data on a large sample of elderly (median age, 76 years) stage III colon cancer patients. Gross and colleagues demonstrated reduced use of adjuvant therapy when patients had coexisting congestive heart failure, diabetes or chronic obstructive lung disease. However, for those that were treated, there was a demonstrable survival advantage.
Source: Gross GP, et al. Cancer. 2007;109:2410-2419.
It has long been suspected that the presence of comorbidity influences both the use and effectiveness of chemotherapy. To address this issue, Gross and colleagues at Yale University queried the Surveillance, Epidemiology, End Results-SEER Medicare Claims database to explore whether patients with comorbidity that included stage III colon cancer between the years 1993 and 1999 were treated with adjuvant chemotherapy. Specifically, the correlations between receipt of adjuvant chemotherapy in the presence of heart failure, diabetes, and/or chronic obstructive pulmonary disease were assessed. Multivariable regression analysis was used to assess the risk of death or hospitalization as a function of treatment and comorbidity status.
The sample included 5330 patients from the SEER database. This population-based tumor registry has been linked with Medicare Administrative Claims data and includes in addition to those claims, characteristics such as cancer type, site, histologic grade, and disease staged. For this analysis, patients aged greater than 67 years (median age for the sample studied, 76 years) were diagnosed with primary adenocarcinoma of the colon. Medicare claims data were used to identify those with existing comorbidity.
Of the 5330 patients in this analysis, it was found that the use of adjuvant therapy was related significantly to heart failure (36.2% for those with heart failure and 64.9% for those without). The adjusted odds ratio (OR) was 0.49; a 95% confidence interval (95% CI) was 0.40 to 0.60. Similar but less robust findings were observed for COPD (OR, 0.83; 95% CI, 0.70 to 0.99) and diabetes (OR, 0.81; 95% CI, 0.68 to 0.97). Among patients who had heart failure, the five-year survival was significantly higher among those who received adjuvant chemotherapy (adjusted five-year survival rate, 43%; 95% CI, 40% to 47%) than among those who did not receive adjuvant chemotherapy (30%; 95% CI, 27% to 34%). Among patients without heart failure, the five-year survival estimates among treated and untreated patients were 54% (95% CI, 52% to 56%) and 41% (95% CI, 38% to 44%), respectively. The probability of all cause, condition specific, or toxicity-related hospitalization associated with adjuvant therapy was not altered by the presence of any of the three comorbid conditions.
Commentary
It will probably come as no surprise to practicing oncologists that adjuvant chemotherapy was offered less commonly in this older age group with existing comorbidity. In fact, even in the absence of comorbidity there was a relatively low rate of adjuvant chemotherapy offered (approximately 65% of patients).
This reflects practice patterns of approximately a decade ago, and possibly the numbers would be better today inasmuch as there have been reported trials indicating the effectiveness of adjuvant chemotherapy in this age group.1,2 Of the three study comorbidities, CHF appeared to have the largest negative impact upon the offering of adjuvant chemotherapy. This may be because physicians are aware that congestive heart failure itself is associated with limited survival and the drugs used for adjuvant chemotherapy might have been considered to negatively influence the effectiveness of congestive heart failure treatment. Nonetheless, it is gratifying that for those patients who had stage III colon cancer and CHF, the benefits of adjuvant chemotherapy were clearly apparent. The five-year survival was significantly higher for those who received adjuvant chemotherapy than for those who did not (43% vs 30%). Furthermore, the hospitalization rate for all treated patients (with or without any of the three comorbidities) was not different. Thus, this report should bolster the moxie of oncologists when approaching the more typical older patients with recently diagnosed stage III colon cancer. The presence of comorbidity is not an absolute contraindication to therapy as its effectiveness has been clearly demonstrated in the community for those selected patients who were treated.
References
1. Iwashyna TJ, Lamont EB. J Clin Oncol. 2002;20:3992-3998.
2. Sargent DJ, et al. N Engl J Med. 2001;345:1091-1097.