LOS ANGELES--For patients with refractory metastatic breast cancer,
ideal therapy would offer palliation with ease of administration and
limited side effects. The new agent capecitabine (Xeloda) can be
taken orally at home, making it unique among currently available
salvage regimens for metastatic breast cancer, Joanne L. Blum, MD,
PhD, of Texas Oncology, Dallas, said at the 34th Annual Meeting of
the American Society of Clinical Oncology (ASCO).
She reported the results of an open-label phase II trial of
capecitabine in heavily pretreated patients. "For patients with
metastatic breast cancers refractory to anthracyclines and taxanes,
effective treatments without severe side effects are limited,"
she said. "The ideal agent would offer a reasonable chance for
response without a substantial risk of prohibitive toxicities."
Capecitabine is a novel, selectively tumor-activated fluoropyrimidine
carbamate. It is an oral prodrug of 5-flourouracil (5-FU) that is
first metabolized in the liver, limiting systemic exposure to 5-FU
(see box). With capecitabine, concentrations of 5-FU in tumor have
been shown to be much higher than in plasma.
Capecitabine Maximizes Tumor Exposure to 5-FU
After oral administration and gastrointestinal absorption,
"Pharmacokinetic studies have shown that intratumoral
The trial, conducted at 25 centers in the United States and Canada,
enrolled 162 patients who had progressed after receiving two or three
prior chemotherapy regimens, one of which had to include paclitaxel
(Taxol). Most patients (84%) had received prior doxorubicin; other
prior treatments included cyclophosphamide, 5-FU, methotrexate, and
Sixty-two of the women were pre-menopausal and 100 were
postmenopausal. The median time from initial diagnosis to recurrence
was 2.5 years.
Capecitabine was given twice daily, to a total dose of 2,510
mg/m²/day, in 3-week cycles (2 weeks on the drug followed by a
1-week rest period).
Responses were seen in 27 (20%) of the 135 patients with measurable
disease (3 complete and 24 partial responses) and occurred in
visceral, soft tissue, and breast involvement sites. Disease remained
stable in 54 patients (40%). "Therefore, 60% had responses or
remained stable," Dr. Blum said. She noted that 46 of these
patients (34%) had progressive disease within the first 6 weeks of
capecitabine treatment (8 patients had missing or incomplete data).
Of the 27 patients with clinically evaluable disease, 5 (19%) had a
tumor response; 12 (44%) were stable; and 10 (37%) progressed on capecitabine.
Overall, the median duration of response was 241 days and median
survival was 384 days. "So, in summary," Dr. Blum said,
"a strong response was seen in a heavily pretreated patient
population with an excellent duration of response and long
survivals." In addition, she said, 47% of symptomatic patients
had a significant pain response with capecitabine.
In general, adverse events were easily managed with dose reductions,
she said. Diarrhea, hand-foot syndrome, and stomatitis were the most
common treatment-related adverse events. Grade 4 adverse events
occurred in 4% of patients, and 7% withdrew due to treatment-related
events; 10% required hospitalization, primarily for dehydration
secondary to diarrhea. No alopecia or significant myelosuppression
was reported, and there were no treatment-related deaths.
"Capecitabine offers treatment without patients having to
endure venipunc-ture, IV infusion, and long intervals in the
chemotherapy infusion suite or long-duration infusional therapy via
indwelling catheters and pumps," Dr. Blum said. "Patients
have expressed a striking 9 to 1 preference for oral palliative therapy."
Discussant William Gradishar, MD, Northwestern University, said that
"the duration of survival in this heavily pretreated patient
population was quite good at 1 year. Most important, palliation was
achieved; about 50% of patients had better pain control on capecitabine."