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SAN ANTONIO (EGMN) - Advanced patient age doesn't diminish the efficacy of paclitaxel for metastatic breast cancer, but it does increase the incidence of selected toxicities, according to a Cancer and Leukemia Group B combined analysis of two phase III trials.
Particularly noteworthy is the age-dependent increase in both neurosensory and neuromotor toxicity due to single-agent paclitaxel (Taxol), Dr. Stuart M. Lichtman said at the San Antonio Breast Cancer Symposium.
The time to development of grade 3 or more neurotoxicity is accelerated in older patients, particularly when paclitaxel is given as second-line therapy, according to Dr. Lichtman of Memorial Sloan-Kettering Cancer Center, New York.
"For elderly patients the neuropathy is a big issue because a lot of them experience functional consequences - falls, other disability of some sort. Patients will stop driving, stop doing other things. It creates a whole social issue," he noted in an interview.
Paclitaxel-induced neurotoxicity is often not reversible within the remaining life span of patients with metastatic cancer. Pregabalin (Lyrica) "helps a little" for painful neuropathy and is somewhat less sedating than gabapentin (Neurontin), but its high cost is an issue for many older people, Dr. Lichtman observed.
He presented a combined analysis of CALBG trials 9342 and 9840 totaling 1,048 paclitaxel-treated metastatic breast cancer patients, 57% of whom received the drug as first-line therapy. First-line therapy elicited significantly higher tumor response rates than second-line therapy; however, response rates were similar regardless of whether patients were under age 55, were 55-64 years old, or were age 65 or older.
"There's an assumption by many oncologists that older people on paclitaxel get more side effects, but if you look at the whole spectrum of toxicity, it's not much different. The neuropathy, though, is different" because of the age-dependent accelerated onset, said the geriatric oncologist, who is on the CALBG Cancer in the Elderly Committee.
Other grade 3-plus toxicities that increased linearly with age were leucopenia, granulocytopenia, and anorexia (see chart). In contrast, rates of severe infection, anemia, diarrhea, stomatitis, nausea, and vomiting were unrelated to age.
"I like to drive home the point that age is not really an issue in the benefit of paclitaxel. It might be to some extent in ovarian cancer but not in breast, colon, or lung cancer. But I think we have to be mindful of the toxicities older patients get. You can't really prevent these problems, but at least you can talk to patients about the likelihood they're going to get them," Dr. Lichtman continued.
The CALBG 9342 trial (J. Clin. Oncol. 2004;22:2061-8) compared paclitaxel at dosages of 175 mg/m², 210 mg/m², and 250 mg/m² given as a 3-hour infusion every 3 weeks. CALBG 9840 (J. Clin. Oncol. 2008;26:1642-9) evaluated paclitaxel given once weekly at 80 mg/m² over a 1-hour period to the drug given at 175 mg/m² over a 3-hour period every 3 weeks.
Dr. Lichtman reported that he had no financial conflicts of interest related to these studies.
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