Capecitabine Studies Show Flexible Dose Effective, Recurrent Breast Cancer Responsive

New data from a pair of studies presented at the 36^th 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 Baylor–Charles 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 for toxicity.

“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 verify this.”