Idarubicin Paired With Capecitabine as Entirely Oral First-Line Treatment

March 1, 2003

EDINBURGH-Idarubicin (Idamycin) paired with capecitabine (Xeloda) and administered orally is well tolerated and active as a first-line treatment for older women with breast cancer, according to results of a recent dose-finding study. The oral idarubicin/capecitabine regimen was associated with 8 responses among 16 postmenopausal women who had chemotherapy-naive locally advanced or metastatic breast cancer, according to David Cameron, MD, senior lecturer in oncology at Western General Hospital, University of Edinburgh.

EDINBURGH—Idarubicin (Idamycin) paired with capecitabine (Xeloda) and administered orally is well tolerated and active as a first-line treatment for older women with breast cancer, according to results of a recent dose-finding study. The oral idarubicin/capecitabine regimen was associated with 8 responses among 16 postmenopausal women who had chemotherapy-naive locally advanced or metastatic breast cancer, according to David Cameron, MD, senior lecturer in oncology at Western General Hospital, University of Edinburgh.

"We were trying to find an entirely oral combination for treatment, and this investigation was really to find the optimum dose," Dr. Cameron said. "We were not looking for how active it was, although we did see responses at every dose level."

Similar Efficacy

Capecitabine has been shown to be at least as effective as paclitaxel or the regimen of cyclophosphamide, methotrexate, fluorouracil (CMF) in advanced breast cancer, according to Dr. Cameron. The oral anthryacline idarubicin is active as a single agent in breast cancer, and has similar efficacy compared with doxorubicin, but with less cardiotoxicity, he added.

Women in the phase I dose-finding study had to be less than 75 years of age; the actual age range was 53 to 75 years. The patients could not have received prior chemotherapy, except for adjuvant CMF completed at least a year earlier. Prior endocrine therapy was also allowed.

Patients received idarubicin on the first 3 days and capecitabine on the first 14 days of a 21-day cycle. Idarubicin was given initially at 10 mg/m2 daily, and capecitabine in divided doses as 1,500, 2,000, or 2,500 mg/m2 per day. The maximum tolerated dose level was idarubicin 10 mg/m2/day and capecitabine 1,250 mg/m2 twice daily. Dose-limiting toxicities included diarrhea and myelotoxicity.

Subsequently, investigators evaluated the 1,000 mg/m2 twice daily dose of capecitabine with a somewhat higher dose of idarubicin (12 mg/m2/day), and found the combination to be tolerable. This dose level is currently being explored in an extended cohort of 12 patients to confirm activity. "This is potentially an active regime that is well tolerated," Dr. Cameron said.

Of the 16 patients enrolled, 13 were evaluable for response. Investigators reported eight responses overall, evenly distributed among the four dosage regimens evaluated.

Some Serious Toxicities

Serious toxicities included grade 3/4 diarrhea in four patients, and grade 3 neutropenia in four patients. A few cases of grade 1/2 nausea and vomiting were reported. Hand-foot syndrome of "very modest" grade 1 severity occurred in three patients.

Alopecia was observed in one patient in each dose group. "Even at the top dose levels, we don’t see a lot of alopecia," Dr. Cameron remarked. There were no significant changes in ejection fraction for any dose level.

Although many women with advanced breast cancer would prefer to receive an all-oral chemotherapy regimen, some are wary of accepting chemotherapy without needles, Dr. Cameron said. Notably, women in this study who had previously taken oral hormone tablets were sometimes hesitant to accept further oral therapy. "Other women did not have (oral hormone) tablets, and they were quite happy to have tablet chemotherapy," he noted.