Adjuvant Chemotherapy for Older Patients
Adjuvant Chemotherapy for Older Patients
By Gary R. Shapiro, MD, Medical Director, Cancer Center of Western Wisconsin, New Richmond, Wisconsin. Dr. Shapiro reports no financial relationships relevant to this field of study.
Synopsis: Four large data sets were analyzed to evaluate the effect of adjuvant treatment on survival in patients with stage III colon cancer diagnosed after age 75. While adjuvant chemotherapy was associated with a survival benefit, oxaliplatin-based regimens offered no more than a small incremental benefit over non-oxaliplatin-containing regimens.
Source: Sanoff HK, et al. Effect of adjuvant chemotherapy on survival of patients with stage III colon cancer diagnosed after age 75 years. J Clin Oncol 2012;30:2624-2634.
To assess outcomes in the general population of older patients, Sanoff and her colleagues gathered data from four observational data sources: the Surveillance, Epidemiology, and End Results registry linked to Medicare claims (SEER-Medicare); the New York State Cancer Registry (NYSCR) linked to Medicare claims; the Cancer Care Outcomes Research & Surveillance Consortium (CanCORS); and the National Comprehensive Cancer Network (NCCN) Outcomes Database. All 5489 patients had stage III adenocarcinoma of the colon (excluding rectal cancer), received chemotherapy within 120 days of surgery, and were 75 years or older at the time of diagnosis.
Use of adjuvant chemotherapy declined with age and comorbidity. Multivariate analysis showed age to be the most strongly associated factor: 63% of patients aged 75 to 79 years, 43% of those aged 80 to 84 years, and 14% of patients 85 years of age and older. The same SEER-Medicare analysis found 46% of patients in the 75 to 79 age group who were treated with chemotherapy received oxaliplatin, compared to 25% of the 80 to 84 group and only 7% of those aged 85 years and older.
Survival was better in those patients who received adjuvant chemotherapy than those who did not (HR 0.60; 95% confidence interval [CI], 0.53 to 0.68 in the SEER-Medicare analysis), but the incremental benefit of oxaliplatin over non-oxaliplatin-containing regimes was seen in only two of the three data sets analyzed (SEER-Medicare HR 0.84; 95% CI, 0.69 to 1.04; NYSCR-Medicare HR 0.82, 95% CI, 0.51 to 1.33).
Commentary
Half of colorectal cancer deaths occur in people older than age 75, and 40% of all colorectal cancer diagnoses are in those 75 years of age or older. Sanoff's database analysis of the 40% in this group who present with stage III disease showed that many do not receive life-saving adjuvant chemotherapy,1 despite overwhelming data in this and others studies2,3,4 that the benefits of adjuvant chemotherapy in older patients are similar in younger and older individuals.
Of note is Sanoff's observation that elderly black patients appear less likely to receive adjuvant chemotherapy than their white counterparts. Although the small sample size included too few African Americans to draw any definite conclusions, this would not be inconsistent with other reports,5 and it should remind us of the urgent need to develop strategies to overcome health care disparities in minority and underserved populations.
Sanoff found that those patients 75 years of age and older treated with adjuvant chemotherapy had a markedly lower risk of death than those who did not receive treatment (32% vs 47% 3-year death rate in the SEER-Medicare database). This effect was comparable to that in previously published studies. This is particularly significant given the fact that more than three-quarters of stage III colon cancer recurrences are within 3 years of diagnosis, well under the life expectancy of the average 75-year-old (9 to 12 years) or 85-year-old (5 to 7 years). Even an unhealthy 75-year-old man or woman will live 5 to 7 more years; long enough to suffer symptoms and early death from recurrent colon cancer.
Although previous subgroup analyses of key randomized, controlled trials showed equal efficacy in seniors getting adjuvant chemotherapy for stage III colon cancer, Sanoff et al wanted to see if this benefit was just as prevalent in older patients treated outside of a formal clinical trial in the community setting. Indeed, they found that the survival value of adjuvant chemotherapy was remarkably similar.
Sanoff and her colleagues believed that this type of comparison was especially warranted when considering the role of oxaliplatin in adjuvant colon cancer regimens. Although oxaliplatin increased cure rates in clinical trials, these studies included very few patients 75 years or older.4 Both the SEER-Medicare and NYSCR-Medicare database analyses confirmed the previously reported 5% absolute improvement in survival at 3 years in patients treated with oxaliplatin-based regimens, but, like the formal clinical trials, the relatively small sample sizes in the database analyses limited Sanoff's ability to draw definitive conclusions about the benefit of these regimens in the elderly.
Unfortunately, this study does not shed much light on the quality-of-life considerations that often are more important than longevity when deciding whether to treat older individuals with cancer. This is especially important when one considers the relatively high incidence of oxaliplatin-induced peripheral neuropathy that can lead to debilitating mobility abnormalities and falls in older individuals. Diarrhea, mucositis, nausea, and vomiting also are more frequent with oxaliplatin-containing regimens. Even though older patients appear to be at no more risk of these side effects than younger patients,2 they are susceptible to adverse events related to secondary dehydration.
Like the randomized, controlled studies, the Sanoff analysis establishes the efficacy and safety of adjuvant chemotherapy in elderly colon cancer patients. It also calls attention to the holes in our knowledge due to the lack of sophisticated geriatric assessments that help determine risk and benefit in this heterogeneous group of patients.
References
1. Muss HB. Adjuvant chemotherapy in older patients with stage III colon cancer: An underused lifesaving treatment. J Clin Oncol 2012;30:2576-2577.
2. Sargent DJ, et al. A pooled analysis of adjuvant chemotherapy for resected colon cancer in elderly patients. N Engl J Med 2001;345;1091-1097.
3. Iwashyna TJ, et al. Effectiveness of adjuvant fluorouracil in clinical practice: A population-based cohort study of elderly patients with stage III colon cancer. J Clin Oncol 2002;20:3992-3998.
4. Goldberg RM, et al. Pooled analysis of safety and efficacy of oxaliplatin plus fluorouracil/leucovorin administered bimonthly in elderly patients with colorectal cancer. J Clin Oncol 2006;24:4085-4091.
5. Shavers VL, et al. Racial and ethnic disparities in the receipt of cancer treatment. J Natl Cancer Inst 2002;94:334-357.
Four large data sets were analyzed to evaluate the effect of adjuvant treatment on survival in patients with stage III colon cancer diagnosed after age 75. While adjuvant chemotherapy was associated with a survival benefit, oxaliplatin-based regimens offered no more than a small incremental benefit over non-oxaliplatin-containing regimens.Subscribe Now for Access
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