Adjuvant Chemotherapy for Elderly Stage III Colon Cancer Patients

Abstract & Commentary

By William B. Ershler, MD

Synopsis: In a retrospective review of adjuvant chemotherapy for elderly (≥ 75 years) patients with stage III colon cancer, performance status and comorbidities were important treatment decision factors. Disease recurrence rates were not different for those who received adjuvant treatment vs those who did not, but 1-year and 5-year survival was significantly better for the treated group. The difference at 5 years remained apparent in multivariate analysis controlling for age, performance status, and comorbidities.

Source: Hoeben KWJ, et al. Treatment and complications in elderly stage III colon cancer patients in the Netherlands. Ann Oncol 2013;24: 974-979.

Much has been written about recognition and treatment of cancer in the elderly. This is particularly relevant because for many of the common tumors, the median age approaches 70 years or more. It is clearly understood that the elderly are not well represented in clinical trials and thus the application of evidence-based standard treatments is problematic. Such standards are often impractical based on age-associated physiological changes or, more commonly, on the existence of comorbidities, social factors (transportation, finances, etc.), or patient and family preferences. Such was the foundation for the research by Hoeben and colleagues in the Netherlands. They conducted a retrospective analysis of tumor registry data to examine factors associated with the selection of adjuvant chemotherapy for stage III colon cancer among patients 75 years and older and compared outcomes, notably, overall survival and various measures of toxicity among those who received adjuvant therapy and those who did not.

To accomplish this, population-based data from five regions included in the Netherlands Cancer Registry were used. Patients with resected stage III colon cancer aged ≥ 75 years diagnosed in 1997-2004 who received adjuvant chemotherapy (n = 216) were included as well as a random sample (n = 341) of patients who only underwent surgery.

The most common explanations for withholding adjuvant chemotherapy were a combination of high age, comorbidity, and poor performance status (PS, 43%) or refusal by the patient or family (17%). In 57% of patients receiving chemotherapy, adaptations were made in treatment regimens. Patients who received adjuvant chemotherapy developed more complications (52%) than those with surgery alone (41%).

Of the total population under analysis (517 elderly patients) who had survived at least 30 days after surgery, 211 patients (41%) developed recurrence of disease. The median time to recurrence was 420 days (4-2629 days). There was no significant difference between both treatment groups. However, for patients not receiving adjuvant chemotherapy, mortality in the first year after surgery was relatively high (33%) compared with 6% in the adjuvant treatment group. Five-year survival for the patients who had survived the first year after surgery remained significantly better for those who had received adjuvant chemotherapy (52% vs 34%, P < 0.0001). This effect remained significant after adjustment for differences in age, comorbidity, and PS (hazard ratio, 0.73; 95% confidence interval, 0.55-0.98). Other independent negative prognostic factors in multivariate survival analysis were advanced age (> 80 years) and extensive comorbidity.

Despite significant rates of chemotherapy-related toxicity and the frequent need for treatment schedule modifications (in approximately 50%), elderly patients who received chemotherapy seemed to have a better 1- and 5-year survival rate.

Commentary

This was a descriptive, retrospective review open to a number of explanations, one of which was that the administration of adjuvant chemotherapy had beneficial effects in terms of survival. However, as the authors clearly point out, alternative explanations are also quite reasonable. Prime among these would be that patients who were relatively fit were more likely to be offered adjuvant chemotherapy. The data clearly indicated that those who did not receive adjuvant chemotherapy had a worse performance score and significantly more comorbidity. Yet, the 5-year survival remained superior for those receiving adjuvant therapy even when data were adjusted for age, comorbidity, and performance status.

The analysis included registered patients from 1997 through 2004 and thus, the great majority received 5FU-leukovorin (87%) whereas only 1% received a combination including oxaliplatin. Data from younger patients would suggest that measures of adjuvant therapy efficacy would be improved by the inclusion of oxaliplatin,1 but such would possibly be less well tolerated in those over 75 years.2

Clearly, continued clinical research including the development of appropriate assessment models for identifying those elderly patients for whom the risk/benefit ratio for adjuvant chemotherapy is favorable as well as additional prospective studies to determine optimal age-specific treatment regimens for elderly colon cancer patients is warranted.

References

1. Andre T, et al. N Engl J Med 2004;350:2343-2351.

2. Goldberg RM, et al. J Clin Oncol 2006;24:4085-4091.