Phase II clinical trial of titanocene dichloride in patients with metastatic breast cancer

Background: Titanocene dichloride (MKT4) is a recently developed cytostatic agent that shows preclinical activity against human breast cancer xenograft models in nude mice. A phase II trial was conducted to evaluate the clinical activity of this inorganic early-transition metal complex in patients with metastatic breast cancer. Patients and Methods: Fifteen patients were enrolled into this multicenter phase II trial. Twelve patients with a median age of 58 years were eligible for toxicity and response. All 12 patients had prior surgery and metastatic disease at study entry. Seven patients had prior radiotherapy, 9 patients had prior hormone therapy, and 8 patients had prior adjuvant chemotherapy. No previous chemotherapy for metastatic disease was allowed. Titanocene dichloride was intravenously administered at a dose of 270 mg/m(2) every 3 weeks. Results: Among the 12 eligible patients evaluable for response, no objective remission was observed. Two patients (17%) showed a 'minor remission: and 5 patients (42%) experienced a 'no change' situation of their disease. Moderate to severe drug-related toxicities (CTC grade II-III) affecting the gastrointestinal, neurological, hepatic and renal system occurred in the majority of patients. Therefore, in 5 patients the dose had to be reduced to 240 mg/m(2). Conclusion: MKT4, given at a dose of 240-270 mg/m(2) in this schedule, was not effective in patients with metastatic breast cancer. The tolerability of the 3-weekly dosing regimen was acceptable when the MKT4 dose was reduced to 240 mg/m(2).