Doxorubicin plus ifosfamide as salvage treatment for patients with advanced breast cancer refractory to epirubicin plus cyclophosphamide

Objective: To investigate the response and toxicity of a salvage regimen in patients with advanced breast cancer whose tumours became resistant to flu orouracil-epirubicin-cyclophosphamide (FEC). By substituting doxorubicin fo r epirubicin and ifosfamide for cyclophosphamide, we aimed to evaluate the possible lack of cross-resistance between the two anthracyclines and the tw o alkylating agents. Patients and Participants: The study included 37 evaluable patients with hi stologically or cytologically proven breast cancer and evidence of progress ive metastatic disease whose disease had progressed under FEC chemotherapy (15 patients) or had recurred within 6 months after FEC chemotherapy (22 pa tients). Interventions: A regimen of intravenous doxorubicin 50 mg/m(2) on day 1 plu s intravenous ifosfamide 5 g/m(2) delivered over 2 days with mesna plus int ravenous fluorouracil 600 mg/m(2) on day 1 was administered every 4 weeks. Nonresponding patients after two courses of treatment received intravenous paclitaxel 175 mg/m(2) over 3 hours. Results: Objective response was achieved by eight patients, with one comple te and seven partial responses (21%; 95% confidence interval 10 to 38%). Me dian response duration was 3 months (range 2 to 7 months), time to progress ion was 5 months (3 to s months) and survival was 8 months (4 to 20 months) . Myelotoxicity was significant, with five episodes of neutropenic fever, a nd 10 patients developed congestive heart failure. Cardiac toxicity develop ed in patients who received a median cumulative dose of >200 mg/m(2) of epi rubicin plus 400 mg/m(2) of doxorubicin. Conclusion: Administration of doxorubicin plus ifosfamide in patients with tumour recurrence after FEC chemotherapy represents a moderately effective regimen, suggesting that the two anthracyclines and the two alkylating agen ts sequential administration of anthracyclines precludes use of this regime n in patients with impaired cardiac function and in those who have received a cumulative dose of anthracyclines >600 mg/m(2).