A multistep randomized phase II/III trial comparing oxaliplatin (OXA)+5 fluorouracil (FU) to vinorelbine (VIN)+FU (FUN) after taxane (T)/anthracycline (A) failure in advanced/metastatic breast cancer (MBC) patients (pts): Final results

Abstract

660 Background: OXA is a new DACH platinum (Pt) with preclinical evidence of activity in vivo and in mammary cell lines. Previous clinical study has shown promising activity both for OXA alone (Ann Oncol 2001 Feb 12(2):179–82) and with FU (JCO 2002 15;20:2551–8) in pretreated MBC. Methods: In order to compare tolerance and activity of OXA/FU to reference regimen FUN in pts pretreated with both T and A, we conduct a randomized phase II-III trial. Pts are assigned either to OXA 130 mg/m2 2 hours IV on day (D) 1 plus FU 750 mg/m2 daily by continuous IV infusion D1 to D5 q 3 wks or VIN 25 mg/m2 IV bolus plus the same FU. Eligibility criteria included relapsing progressive MBC, at least one previous chemotherapy (CT) for MBC, no more than 3 prior CT, previous A, previous T therapy given for MBC in an appropriate dose and schedule, at least one measurable target lesion (RECIST criteria), WHO PS 0–2, adequate baseline organs functions. Stratification factors: institution, best response to T: PR or CR vs no response, visceral site: yes vs no, number of previous chemotherapy lines in metastatic disease: 1 vs 2. Efficacy was evaluated by radiological assessment every 6 wks; responses are confirmed at least 4 wks later. Results: Between 7/00 and 7/02 137 Pts have been randomized in 33 centers (68 in OXA arm and 69 in VIN arm). Main pts characteristics, safety (G 3–4 AE by pts) and efficacy (RR, PFS, OS) results are shown in the table below. The study was prematurely discontinued due to accrual difficulty related to competitive drugs introduced (Capecitabine®) in the same clinical setting. Conclusion: OXA-5FU combination achieve similar results in term of RR, PFS and OS and favorable safety profile when compared to VIN-5FU combination which is one of the most active CT regimen in post taxane MBC. No significant financial relationships to disclose.