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(Drug information on 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."