Portyansky, Elena, Drug Topics
Targeted breast cancer drug offers better tolerability profile
Perhaps modeled after the great magic bullet theory, a recently approved oral, tumor-activated antineoplastic agent appears to aim its cytotoxic ammo at the tumor, while bypassing healthy tissue.
Manufactured by Hoffmann-La Roche, Xeloda (capecitabine) is indicated for the treatment of patients with metastatic breast cancer who are resistant to both paclitaxel and an anthracycline-containing regimen. These regimens, noted Mike Carrol, an oncology R.Ph. at Park Medical Center in Columbus, Ohio, usually include cyclophosphamide and 5-fluorouracil (5-FU), with either methotrexate or doxorubicin. Patients who fail these treatments face few options, one of which is a continuous infusion of 5FU.
Fabio Benedetti, M.D., medical director of oncology at Roche, explained that capecitabine, a fluoropyramide carbamate, undergoes enzymatic conversion to mostly inactive intermediate compounds until it reaches the tumor site, where it's converted to active 5-FU by thymidine phosphorylase. The enzyme is highly concentrated in tumors and found in low concentrations in normal tissues.
In a phase II trial, 18.5% of patients whose tumors were no longer responding to the aforementioned regimens experienced a reduction in tumor size of more than 50% after receiving capecitabine. One patient underwent a complete remission.
Because of capecitabine's selective tumor activation, common chemotherapy-related adverse effects, such as alopecia and bone marrow suppression, are minimized. Carrol noted that "although current 5-FU is relatively well tolerated, compared with other antineoplastic agents, the drug is surely not without its side effects."
Capecitabine's most frequently reported adverse effects, which were generally manageable and reversible after dosage adjustment, included diarrhea, nausea, vomiting, fatigue, stomatitis, and handfoot syndrome (palms of the hands or soles of the feet tingle or become numb, painful, swollen, or red). Potentially serious risks associated with the drug include severe diarrhea, grade 3 or 4 neutropenia, thrombocytopenia, and decreases in hemoglobin.
The recommended dose of capecitabine is 2,500 mg/m^sup 2^ in two divided oral doses at the end of a meal for two weeks, followed by a one-week rest period, given in threeweek cycles. …