ROCHESTER, MinnesotaDespite 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 theyre 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 patients age, and to learn whether elderly patients
experience more toxicity from adjuvant therapy than younger patients
For the first goal, the endpoints were overall survival and time to
tumor recurrence. For the second goal, the endpoint was grade 3 or
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.
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
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 levamisoles 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.
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.