ORAL DOXIFLURIDINE PLUS LEVOLEUCOVORIN IN ELDERLY PATIENTS WITH ADVANCED BREAST-CANCER

BACKGROUND. There currently is no agreement regarding the appropriate treatment of elderly patients with advanced breast carcinoma (ABC). Do xifluridine (5-dFUR), a prodrug of 5-fluorouracil, has been found to b e effective in this entity, but its use is limited by neurotoxicity an d cardiotoxicity that are not observed when the oral formulation is us ed. The objective of this Phase II trial was to evaluate the effective ness and tolerability of oral 5-dFUR, biomodulated with levoleucovorin (l-leucovorin), in elderly patients (age > 70 years) with ABC. METHOD S. 5-dFUR was administered orally at 600 mg/m(2) twice daily for 4 con secutive days every 12 days, and oral l-leucovorin was administered as 25 mg 2 hours before each 5-dFUR administration. Response was assesse d every five cycles according to the World Health Organization criteri a. In the presence of response or stable disease, the patients were tr eated for a maximum of 15 cycles. RESULTS. Seventy-three eligible pati ents were enrolled, 27 of whom had been pretreated with chemotherapy a nd/or hormonotherapy; all were assessable far response and toxicity af ter a median follow-up of 15 months. The objective response rate was 2 6% (95% confidence interval, 17.4-45.4). Regression predominantly occu rred in the presence of soft tissue involvement (skin, lymph nodes, an d breast). The median time to response was 2 months (range, 1-2 months ) and the median response duration was 7 months (range, 2-17+ months). The median survival was 24 months (range, 2-42+ months). The treatmen t was very well tolerated, and the side effects were manageable and al ways reversible. CONCLUSIONS, The results of the current study show th at 5-dFUR plus l-leucovorin, both given orally, are associated with ex cellent patient compliance. Although the results are suboptimal in ter ms of an objective response, this characteristic could allow 5-dFUR to be used in elderly patients considered unsuitable for ''aggressive'' chemotherapy. (C) 1998 American Cancer Society.