AVIANO, Italy--Elderly women with node-positive breast cancer are
more vulnerable to chemotherapy-related toxicity. Physicians should
be prepared to help older patients prevent or manage these problems
and should not be too quick to reduce scheduled dosages, Diana
Crivellari, MD, said at her ASCO poster presentation for the
International Breast Cancer Study Group (IBCSG) Trial VII.
In this study, women over age 65 had a higher incidence of side
effects from the classic cyclophosphamide/methotrexate/fluorouracil
(CMF) schedule than younger women, Dr. Crivellari said.
She advised physicians to be aware of the kinds of toxicity that
might be expected from various regimens in treating elderly patients,
to give the patient thorough information in advance about what
problems may occur and how to cope with them, and to routinely use
simple measures such as cryotherapy with ice and increased water
intake to prevent mucositis and cystitis in elderly patients.
"Toxicity with CMF among patients over age 65 in this trial was
generally moderate, with only one instance of life-threatening
toxicity, a pulmonary embolism," Dr. Crivellari said. "There
were no differences in hepatic or hematologic toxicities in these
older patients. Mucosal toxicity was the reason for dose
reductions." Dr. Crivellari is in the Divisione Oncologia
Medica, Centro di Riferimento Oncologico, Aviano, Italy.
This study included 1,266 postmenopausal breast cancer patients with
node-positive disease (ER+ or ER-). Patients were treated by either
total mastectomy or a breast-conserving procedure followed by local
radiotherapy and then randomized to one of four adjuvant chemotherapy
options (see Table 1). Classic
CMF was planned at full doses without upfront dose reductions, even
in patients older than 65 years.
A total of 906 patients were accrued into the three chemotherapy arms
that included CMF, and 853 were evaluable for toxicity. Differences
according to age were observed both for patients treated with three
consecutive CMF cycles and those given delayed CMF.
The grade of mucositis (oral, gastrointestinal, vesicle), rather than
hematologic or other types of toxic effects, was primarily
responsible for differences in worst toxicity grade according to age
(see Table 2). Patients older
than 70 received less than their expected dose, compared with those
younger than 70.
According to Dr. Crivellari, the breast cancer death rate for
American women declined by 4.7% between 1989 and 1992, but this
improvement was limited to younger women. Adjuvant chemotherapy
reduces relapse and mortality in postmenopausal patients, and dose
reductions of classic CMF are associated with decreased efficacy, so
finding ways to maintain dose intensity is important.
In an interview with Oncology News International, Dr. Crivellari said
that "grade 3 mucosal toxicity is the point at which dose
reduction is considered." She noted that the colony-stimulating
factors can be used for protection, "but they are very expensive."
The approach Dr. Crivellari advises to try to prevent mucosal
toxicity is to give the patient ice to suck on during the infusions
and have the patient use mouthwashes during the following week. Also,
she said, "older women should be advised to drink a lot of water
to avoid treatment-related cystitis caused by excretion of cyclophosphamide."