MANHASSET, New York—Early clinical results suggest that capecitabine(Drug information on capecitabine) (Xeloda) may work well in several new combinations for metastatic breast cancer, according to Daniel R. Budman, MD, professor of medicine at New York University and associate director of medical oncology at North Shore University Hospital, Manhasset, New York.
Beyond its successful pairing with docetaxel(Drug information on docetaxel) (Taxotere), capecitabine may have potential in combination with paclitaxel(Drug information on paclitaxel) (Taxol), vinorelbine (Navelbine), irinotecan(Drug information on irinotecan) (CPT-11, Camptosar), and in triplet therapy with docetaxel and epirubicin(Drug information on epirubicin) (Ellence).
Speaking at an industry-sponsored symposium held in conjunction with the 38th Annual Meeting of the American Society of Clinical Oncology, Dr. Budman said that the docetaxel/capecitabine experience suggests several new directions for combination therapy, including different schedules of giving docetaxel and substituting a different taxane, such as paclitaxel (Taxol).
In a 47-patient phase II study of paclitaxel (175 mg/m² on day 1 every 3 weeks) and capecitabine (825 mg/m² twice a day on days 1 to 14), the median time to progression was more than 44 weeks, and the total response rate was nearly 40% when given as first-line therapy and more than 50% as second-line therapy (see Figure 1).
In another approach, capecitabine is being studied in combination with vinorelbine. Results of three small phase I or II trials indicate overall response rates around 50%.
In one study of 36 women age 65 or older—the Swiss SAKK 25/99 trial—all patients received, as first-line therapy, 20 mg/m² of vinorelbine on days 1 and 8, but the capecitabine dose varied from 800 mg/m² to 1,250 mg/m² twice daily on days 1 to 14. Dose-limiting toxicities were neutropenia, stomatitis, diarrhea, and thrombosis (Hess DD et al: Proc Am Assoc Clin Oncol 21(part 2):247b, 2002, abstract 2915).
"Antitumor responses were seen at all dosage levels," Dr. Budman said. "This brings up a different point because all of us try to use next to the maximum tolerated dose. But if you can get true synergism, it’s entirely conceivable—although we haven’t really clinically studied it up front—to see whether we can give a relatively less toxic combination and yet get the same activity, which then becomes a major quality-of-life advantage."
