Elderly Colon Cancer Patients Benefit From Adjuvant Chemotherapy

ROCHESTER, Minnesota—Fluorouracil (5-FU)-based chemotherapy after surgery can be given safely to selected elderly patients with stage II/III colon cancer, and these patients derive the same benefits from the treatment as do their younger counterparts, according to results of a pooled analysis of seven clinical trials.

Physicians will be seeing growing numbers of elderly patients with colorectal cancer over the next 30 years. By that time, an estimated 20% of Americans will be over age 65, commented lead investigator Daniel J. Sargent, PhD, of the Mayo Clinic.

The Current Standard

Currently, treatment with 5-FU plus leucovorin for 6 to 8 months is standard adjuvant treatment for patients with stage III colon cancer. "The benefits of 5-FU-based therapy for stage II colon cancer are unclear, although many trials permit the enrollment of patients after resection of either stage II or stage III disease," Dr. Sargent said.

He pointed out, however, that elderly patients with stage II/III colon cancer are less likely than younger patients to be offered or to receive adjuvant chemo-therapy. Data from the National Cancer Institute’s Surveillance Epidemiology, and End Results Program (SEER) show that only 48% of patients aged 65 to 74 years received adjuvant chemotherapy for node-positive colorectal cancer, and only 24% of those patients aged 80 to 84.

Reasons for withholding adjuvant chemotherapy from elderly patients may include coexisting conditions, fear of toxicity, declining functional and mental status, and lack of social support, Dr. Sargent said, but "most people older than 75 are independent, and their life expectancy without cancer is 10 to 12 years."

To investigate the effects of adjuvant chemotherapy in the elderly, the researchers pooled data from seven randomized trials comparing 5-FU-based regimens after surgery with no adjuvant chemotherapy for patients with stage II/III colon cancer. Five studies used 5-FU plus leucovorin, and two tested 5-FU plus levamisole.

A total of 3,351 eligible patients were divided into four age groups: age 50 or under (564 patients); 51 to 60 (1,012); 61 to 70 (1,269), and greater than 70 (506).

The oldest patients (older than 70) had a higher probability of dying without evidence of recurrence than the youngest patients (50 or younger) (13% vs 2%), and were more likely to die of causes other than cancer (32% of deaths vs 5% in the younger group). However, the researchers pointed out, most deaths in all age groups were due to colon cancer (about 30% in each group).

Adjuvant Therapy Results in Longer Survival

Overall results from the pooled analysis showed a significantly longer survival for patients receiving adjuvant therapy. Five-year survival was 71% for treated patients vs 64% for untreated patients (P < .001). Five-year recurrence-free survival was 69% vs 58%, respectively (P < .001).

The researchers observed no significant interaction between age and treatment effect for overall or recurrence-free survival (for a complete report, see N Engl J Med 345:1091-1097, 2001).

"The curves for overall survival and freedom from recurrence comparing adjuvant treatment with no adjuvant treatment according to age group were very similar for the 5 years of follow-up," Dr. Sargent commented. "The survival curves for the patients who were older than 70 years of age converged slightly after 5 years, probably because of deaths from other causes."

Older patients receiving chemotherapy did not have a higher incidence of severe (grade 3 or higher) nausea or vomiting, stomatitis, or diarrhea, he said. Rates of severe leukopenia were higher among elderly patients receiving chemotherapy, significantly so in those receiving 5-FU plus levamisole (P < .001) and of borderline significance in those receiving 5-FU plus leucovorin (P = .05).

Dr. Sargent and his colleagues concluded that "there is no evidence that the susceptibility of colon cancer to chemotherapy differs in younger and older patients."

He cautioned that the study results may not be applicable to the general population of older patients, because the trial participants were a select group due to exclusion criteria and screening.

"Although many elderly patients in the community have similar characteristics, others have multiple coexisting conditions, malnutrition, and poor social support," Dr. Sargent said. He concluded that until further studies are conducted, "the decision to treat an elderly patient who has several other problems should involve the physicians, patient, and family."