Ifosfamide combination chemotherapy in advanced breast cancer

The objective of our clinical studies was to develop an effective combination chemotherapy regimen (CHT) with acceptable side effects, consisting of the two most potent drugs used as single agents in breast cancer. We tested the combination of an anthracycline, epirubicin (A) at 70 mg/m2 i.v. on day 1 or (B) at 120 mg/m2 i.v. on day 1 with an alkylating drug ifosfamide (IFO), (C) at 2.5 g/m2 in an i.v. infusion given over 4 h on days 1-3 or (D) at 5 g/m2 in a 24-h i.v. infusion given on day 1. Courses were repeated every 4 weeks. The combinations were given as first-line therapy as follows: CHT (A, C) in six cases and CHT (B, C) in five cases of advanced breast carcinoma, and CHT (B, D) in seven patients with primary inflammatory breast cancer. Due to side effects (e.g., stomatitis, mental disturbances) and applicability, CHT regimen (B, D) was preferred. Responses (12/18) occurred 1-3 cycles earlier than those previously achieved using the conventional epirubicin/cyclophosphamide CHT. We conclude that 5 g/m2 IFO given i.v. over 24 h with uroprotection (mesna) in a two-drug regimen is an effective dose with tolerable toxicity. Alopecia was seen in all cases. However, according to our experience, myelotoxicity is the dose-limiting factor for both of these drugs.