New data from a pair of studies presented at the 36th
annual meeting of the American Society of Clinical Oncology (ASCO)
suggest that capecitabine (Xeloda) doses can be adjusted without
compromising efficacy in patients with advanced breast cancer, and
that capecitabine therapy can reduce tumor sizes by more than 50% in
patients whose breast cancer has recurred after high-dose
chemotherapy with autologous stem-cell support.
In the first study, investigators from Baylor University Medical
Center in Dallas concluded that, in order to help minimize side
effects for patients with metastatic or advanced breast cancer,
physicians can reduce therapy with the oral agent capecitabine to
meet patients individual needs without jeopardizing tumor
response, duration of the response, the time to treatment failure, or
the length of survival.
A high therapeutic index offers the possibility of flexible
drug dosing, which is important for physicians treating women with
metastatic or advanced breast cancer, said Alain Thibault, md,
medical director of Oncology at Roche Laboratories. This study
suggests that the dose of Xeloda can be reduced for those who cannot
tolerate the full starting dose, without compromising efficacy. These
data are also encouraging because Xeloda is being investigated in
combination with several anticancer agents, and flexibility in dosing
is an important factor in combination therapy.
Results of Four Clinical Trials
The retrospective study of four phase II clinical trials conducted at
the BaylorCharles A. Sammons Cancer Center at Baylor University
Medical Center evaluated 321 women with metastatic or advanced breast
cancer. The analysis compared 131 patients who had received reduced
doses of capecitabine with 190 patients who had not.
In patients experiencing significant adverse events, the starting
dose (2,510 mg/m²/d) was administered daily for 2 weeks,
followed by a 1-week rest period. Initially, capecitabine was reduced
by 25% after a median of 49 days and then by 50% after a median of
105 days. Dose reduction had no negative effect on efficacy.
Tumor Size Reduced by More Than Half
In another presentation at ASCO, Dr. Thibault announced that
capecitabine may be an effective treatment for metastatic breast
cancer patients whose disease has recurred after receiving high-dose
chemotherapy with autologous stem-cell support. New data from a phase
II clinical trial show that capecitabine reduces tumor size by more
than half in 70% (7/10) of the patients in the study.
More than 75% of breast cancer patients relapse after high-dose
chemotherapy, and are left with poor prognosis and extremely limited
treatment options, if any, said Dr. Thibault. This study
suggests that Xeloda may be a promising option and should be studied
further in this patient population.
More than 15,000 women with advanced and metastatic breast cancer
have undergone high doses of chemotherapy followed by transplants of
the patients own blood cells to replace bone marrow damaged by
the treatment. To date, this aggressive, arduous procedure has not
shown a survival advantage over conventional therapy. When it fails,
patients have virtually no effective treatment options.
Clinical Trial Design
The phase II study followed 10 patients with metastatic breast cancer
whose disease progressed after high-dose chemotherapy with autologous
stem-cell support. All patients commenced capecitabine at a dose of
2,500 mg/m²/d divided into two daily doses for a 3-week cycle
consisting of 2 weeks of treatment followed by 1 week with no
treatment. Patients received a median of eight cycles of treatment,
ranging from 4 to 24 cycles.
Two patients achieved a complete response and five achieved partial
responses, for an overall response rate of 70%. In addition, three
patients achieved a minimal response or stable disease. Median
follow-up was 279 days after commencing capecitabine therapy, at
which time all patients were alive and five were in remission. Five
patients progressed after remissions that lasted between 124 and 320 days.
In the study, the most common adverse events reported were hand-foot
syndrome, diarrhea, and neutropenia. Adverse events were manageable
and reversible with treatment interruption, dose reduction, and
symptomatic treatment. None of the patients required in-patient care
The lack of hair loss and outpatient administration may prove
to be a benefit to patients, said Asad Bashey, md, phd,
assistant professor of medicine at University of California, San
Diego (UCSD) School of Medicine and director of the unrelated donor
transplant service of the UCSD Blood and Marrow Transplantation
Program. From this trial, Xeloda appears to be active and
tolerable in this patient population that has been extensively
pretreated with chemotherapy, and further studies will be needed to