Induction Intra-arterial Chemotherapy (IAC) with Epirubicin and Mitoxantrone in Locally Advanced Breast Cancer

Abstract

Background: It is known that 15% of patients with breast cancer present with locally advanced disease without distant metastases. This phase II trial is aimed at investigating the activity of epirubicin and mitoxantrone combination as induction intra-arterial chemotherapy (IAC) in locally advanced breast cancer patients.

Patients and Methods: Seventy-two patients with locally advanced disease and no prior exposure to doxorubicin received the following regimen: epirubicin 30 mg/mq and mitoxantrone 10 mg/mq by IAC short infusion on day 1, every 3 weeks for up to six cycles. Prior to IAC, an arteriogram of subclavian, internal mammary, and lateral thoracic arteries was obtained in all patients, followed by infusion of a blue dye solution into the arteries, to determine the most appropriate vessel that supplies the tumor area. Results: Objective responses, confìrmed at least 4 weeks after the first documentation, were observed in 50 patients (70%; 95% CI, 68–84%): 6 CR, 44 PR. Although only six of the patients showed complete tumor regression, operative removal or toilet mastectomy became feasible in all 50 patients since tumor shrinkage was 75% or more. A total of 50 mastectomies were carried out in all 72 patients. At presentation eight patients had bulky tumors (>13 cm tumor diameter), while 16 patients had ulcerated tumors, four of which presented with complete infiltration of normal breast tissue. The median times to progression and median overall survival were 12 and 28 months, respectively. The time to local response was 3 weeks and time to mastectomy was 9 weeks. Transient neurological disorders developed in 12 patients and overlying skin chemical burns with painful inflammatory reactions were encountered in 20 patients. No systemic toxicity was observed in terms of bone marrow depression or hair loss. No cardiotoxicity was observed. In all specimens necrosis was reported (complete 6 cases, partial 32, and minimal 12). Conclusion: A combination of epirubicin and mitoxantrone as IAC appears to be a safe and well-tolerated treatment for locally advanced breast cancer without clinical evidence of distant metastases. When combined with surgery it offers interesting results in terms of local control and allows a high rate of mastectomies in otherwise inoperable cases.