ROCHESTER, Minnesota—Despite their age, people over 70 who have colon cancer can benefit from adjuvant chemotherapy, Daniel Sargent, PhD, assistant professor of biostatistics, Mayo Clinic, Rochester, Minnesota, reported at the 36th annual meeting of the American Society of Clinical Oncology (ASCO).
Two Unanswered Questions
Adjuvant chemotherapy has been controversial in elderly patients because of two unanswered questions, said Richard Goldberg, MD, co-principal investigator of the study and director of GI Cancer Research for the Mayo Clinic Cancer Center, in an interview with ONI.
First, do people over 70 live long enough after adjuvant chemotherapy to benefit from it? And second, do people over 70 have more side effects from adjuvant chemotherapy just because they’re older and possibly less resilient?
The meta-analysis reported at ASCO was designed to answer these questions and had two goals: to determine whether the benefits of adjuvant therapy for stage II and stage III colon cancer depend on the patient’s age, and to learn whether elderly patients experience more toxicity from adjuvant therapy than younger patients do.
For the first goal, the endpoints were overall survival and time to tumor recurrence. For the second goal, the endpoint was grade 3 or higher toxicities.
Drs. Sargent and Goldberg and their coauthors performed a meta-analysis of mature phase III randomized trials that compared surgery plus adjuvant chemotherapy to surgery alone in Dukes’ B2 or C colon cancer patients. Seven studies were included in the analysis, and 15% of their subjects were older than 70. Of these, five studies used 5-fluorouracil (5-FU) plus leucovorin in the chemotherapy arm, and two used 5-FU plus levamisole(Drug information on levamisole).
The researchers broke the 3,351 patients down by age in two ways: first into four age categories of equal size, and second into groups based on decade of life (less than 50 years, 50 to 60 years, 60 to 70 years, more than 70 years).
No matter which age breakdown was used, the results were the same. Both overall survival and time to tumor recurrence were significantly longer in the people on adjuvant therapy. Five-year survival was 71% in patients getting chemotherapy vs 64% in those treated with surgery alone.
Both treatments caused some grade 3 or higher toxicities, although fewer than 20% of patients suffered any one symptom (nausea or vomiting, diarrhea, stomatitis, or leukopenia). Rates of different kinds of toxicities were generally similar between people older than 70 and those 70 and younger, with one exception. People over 70 were significantly more likely to get leukopenia in one of the trials that used 5-FU plus levamisole.
“However, 5-FU/leucovorin has really replaced 5-FU/levamisole,” so levamisole’s greater side effects are mostly of historical interest, Dr. Goldberg told ONI. “When we compared 5-FU/leucovorin regimens, and there were several different regimens in this study, there was no difference in side-effect profile on the basis of age.”
Same Benefit
Dr. Sargent concluded that for patients participating in clinical trials, younger and older patients get the same benefit from adjuvant therapy and people over 70 did not experience significantly more toxicity overall. As a result, age alone is no reason to deny an otherwise healthy person adjuvant chemotherapy.
Extrapolating these results to older people as a whole takes some care, Dr. Goldberg told ONI. The studies included in the meta-analysis had entry requirements: generally, that patients must have recovered from their surgery and have a performance score of 0, 1, or 2. So these results are based on older people who are relatively fit and may not apply to the ill and infirm, he said.
“Patients and their physicians should not eliminate the possibility of taking adjuvant therapy on the basis of age alone, because selected older patients can benefit as much as younger patients without an increase in side effects,” Dr. Goldberg said.
