Combined treatment with fulvestrant plus capecitabine in elderly advanced breast cancer (EABC): Three-year evaluation of efficacy and safety

Background: EABC affects about 45% of all advanced breast cancers and actually treatments are always more toxic than effectiveness. Fulvestrant (F), the first of a new class of pure estrogen receptor antagonists, competitively binds to estrogen receptors on tumors and inhibit tumor growth. Capecitabine (C) is converted to 5-FU by thymidine phosphorylase and shows good efficacy and low toxicity as single agent in EABC. Since elderly cancer pts are extremely susceptible in development of rapid toxicity during treatment with cytotoxic drugs, we design this chemo-hormone combined schedule to evaluate if F + C could increase efficacy profile in EABC women. Methods: 41 EABC pts (mean age 72; range 65-88) PD after TAM or SERM were included in the study starting in 2007. Written informed consent for treatment's schedule was acquired from all pts. Comprehensive Geriatric Assessment (CGA) was performed to assess eligibility for chemotherapy. Furthermore the C dose was adjusted according to Cocroft and Kintzel-Dorr formulas. Primary endpoint: clinical response rates (RR) according to WHO criteria. Secondary endpoints: TTP, Toxicity Profile and QoL score measured by NCI-CTC v2.0 and EORTC QLQ-C30 questionnaires. Results: 41/41 pts were evaluated. All pts received C 1,000 mg/m2 b.i.d p.o. on days 1st to 14th every 21 days and F 250 mg i.m. once-monthly until disease progression. Based on CGA all patients were included into groups I-II, according to Balducci's classification of frailty. None of the pts needed any delay in drugs delivery. We observed 13/41 (32%) partial responses and 17/41 (41%) stable disease, for a Clinical benefit of 73%. Median time to progression was 15,6 months. No grade-4 toxicity was experienced. QoL score improvement was appreciated in all pts after end of treatment. Conclusions: Efficacy and Safety results show that this schedule is feasible for EABC pts affected by one or two comorbidities and also in frail condition. All pts are still alive and under monitoring for long-term toxicity and QoL. These results shows that F+C schedule increase clinical benefit-enhancing effectiveness and safety. Although a larger number of EABC pts must be enrolled to consolidate these findings