Commentary (Extermann): Management of Colorectal Cancer in Older Patients

In their article, Xiao and Lichtman do an excellent job of assembling the available evidence on treating colon cancer in the elderly. It is clear from their review that healthy elderly patients should be offered a wide range of therapeutic options, if not all standard treatments currently available for colon cancer. At the same time, their report illustrates the limitations of how we obtain data on the treatment of older colon cancer patients, and more broadly, of older cancer patients in general.

Three Considerations

The authors' review can be summarized as follows:

(1) Most of the data presented come from retrospective subgroup analyses of large trials in which elderly patients are underrepresented.

(2) These data mostly pertain to the young and "fit" elderly. For example, in the Sargent et al meta-analysis, only 23 of 3,351 patients, or 0.7%, were over 80 years of age. Yet this age group represents one-fourth of colon cancer patients in the population.[1]

(3) These datasets rarely provide any information on comorbidity. This has two consequences. First, these datasets ignore potential confounding factors that can have effects as great as the treatment itself. Consider, for example, Figure 1. The impact of diabetes on disease-free survival is comparable to the impact of adjuvant fluorouracil (5-FU)/levamisole on disease-free survival in stage III colon cancer.[2,3] Therefore an uncontrolled imbalance in diabetic patients could significantly flaw the results of an adjuvant trial. Similarly, an imbalance in inflammatory diseases could skew findings on the use of nonsteroidal anti-inflammatory drugs (NSAIDs).[4]

The second consequence of the lack of comorbidity data is that we are deprived of extremely helpful information when it comes to translating results to the everyday patient. For example, as highlighted by Xiao and Lichtman, patients with major cardiovascular conditions were excluded from the bevacizumab (Avastin) trials. But how many patients had stable coronary artery disease? Or well compensated congestive heart failure? Or vascular renal disease? Or a history of peptic ulcer? Or a diabetic microangiopathy? What was the outcome in these subgroups?

Cooperative Group Studies

Potential strategies to address these issues have been illustrated by three sets of cooperative group studies. The North Central Cancer Treatment Group (NCCTG) conducted two phase II lung cancer trials specifically targeting the elderly in parallel with "regular" phase II studies.[5] They accrued a clearly different population-older and less fit-without competing with accrual into the other studies. Toxicity was less common and survival similar.

The Eastern Cooperative Oncology Group (ECOG) conducted a study targeting patients more than 75 years old with metastatic colorectal cancer. Patients were treated with uracil/tegafur (UFT) and leucovorin. The median age was 81 (range: 75-89), showing that this study indeed accrued very old patients. The drug was well tolerated and the response rate within the expected range for such compounds. The abstract does not provide details on functional status and physical conditions of these patients.[6]

The third set is a pair of European studies targeting frail elderly patients with non-Hodgkin's lymphoma.[reference 7, and Pierre Soubeyran et al, personal communication, International Society of Geriatric Oncology conference, Geneva, Switzerland, Sept 29-Oct 1, 2005]. These investigations provided very helpful information on outcomes in this rarely targeted population, which would never have been enrolled in a "regular" trial.

Conclusions

These studies prove that (1) It is possible to conduct cooperative studies targeting older patients. (2) They accrue a different population than other trials. (3) It is possible to carry out a comprehensive geriatric assessment in a cooperative group study setting. Hopefully, in the future, Xiao and Lichtman will be able to cite many more studies that prospectively target the elderly, with relevant comorbidity and health status information.

-Martine Extermann, MD

Disclosures:

The author(s) have no significant financial interest or other relationship with the manufacturers of any products or providers of any service mentioned in this article.

References:

1. Sargent DJ, Goldberg RM, Jacobson SD, et al: A pooled analysis of adjuvant chemotherapy for resected colon cancer in elderly patients. N Engl J Med 345:1091-1097, 2001.

2. Meyerhardt JA, Catalano PJ, Haller DG, et al: Impact of diabetes mellitus on outcomes in patients with colon cancer. J Clin Oncol 21:433-440, 2003.

3. Moertel CG, Fleming TR, Macdonald JS, et al: Fluorouracil plus levamisole as effective adjuvant therapy after resection of stage III colon carcinoma: A final report. Ann Intern Med 122:321-326, 1995.

4. Extermann M: Biological basis of the association of cancer and aging comorbidity. Cancer Treat Res 124:173-186, 2005.

5. Jatoi A, Hillman S, Stella P, et al: Should elderly non-small-cell lung cancer patients be offered elderly-specific trials? Results of a pooled analysis from the North Central Cancer Treatment Group. J Clin Oncol 23:9113-9119, 2005.

6. Popa EC, Luo W, Hochster H, et al: A phase II study of ORZEL (UFT+leucovorin) in elderly (=75 years old) patients with colorectal cancer: Results of ECOG 1299. J Clin Oncol 23(16S):273s, 2005.

7. Monfardini S, Aversa SM, Zoli V, et al: Vinorelbine and prednisone in frail elderly patients with intermediate-high grade non-Hodgkin's lymphomas. Ann Oncol 16:1352-1358, 2005.