Weekly Vinorelbine Is An Effective Palliative
Regimen after Failure with Anthracyclines and Taxanes in Metastatic Breast Carcinoma W e would like to dispute some of the statements made in the article by Zelek et al. 1 in Volume 92, Issue 9. The authors state that "currently, there is no gold standard for the treatment of patients with metastatic breast carcinoma who have experienced failure with anthracyclines and taxanes." They later mention that "among newer drugs, capecitabine appears to be promising with an [objective response] rate of 20% and a favorable tolerance profile."
Capecitabine (Xeloda; Hoffmann-LaRoche, Nutley, NJ) is the only approved agent for use in this indication and has received regulatory approval in both the United States and Europe. Therefore, from a regulatory standpoint, capecitabine can be considered a reference treatment for patients with anthracycline-and taxanepretreated metastatic breast carcinoma.
Capecitabine is a novel oral fluoropyrimidine carbamate with high activity against metastatic breast carcinoma and a favorable safety profile. By exploiting the significantly greater activity of thymidine phosphorylase against tumor tissue compared with healthy tissue, 2 capecitabine delivers 5-fluorouracil preferentially at the tumor site. In 4 multicenter studies, capecitabine (1250 mg/m 2 twice daily for 14 days, followed by a 7-day rest period) demonstrated considerable antitumor activity in patients with anthracycline-and taxanepretreated metastatic breast carcinoma 3-6 (Table ).
The authors also state that "other agents such as gemcitabine or pemetrexed (MTA, LY231514) are potential candidates, but to our knowledge no specific trial addressing their activity in taxaneresistant patients has been published to date with these drugs." In a recently published report of a Phase II study investigating gemcitabine in this indication, there were no objective responses to gemcitabine, the median time to disease progression was 1.9 months, and the median overall survival was 7.8 months. 7 The investigators in that study concluded that gemcitabine is ineffective in patients with heavily pretreated metastatic breast carcinoma and should not be used in that setting. Gemcitabine therefore appears not to be a potential candidate for treatment of anthracycline-and taxane-pretreated metastatic breast carcinoma. In the study performed by Zelek et al., vinorelbine yielded an objective response rate similar to the rate observed with capecitabine. However, the median overall survival of patients treated with vinorelbine was a disappointing 6 months. In contrast, over the course of four studies, capecitabine consistently has yielded noteworthy activity and survival results in this difficult-to-treat population (Table ).