Carboplatin plus paclitaxel versus carboplatin plus Stealth liposomal doxorubicin in patients with advanced ovarian cancer (AOC): Preliminary activity results of the MITO-2 randomized multicenter trial

Abstract

5532 Background: The MITO-2 (Multicentre Italian Trials in Ovarian cancer) study is a randomized phase III study comparing the effect on progression-free survival of carboplatin/paclitaxel versus carboplatin/stealth liposomal doxorubicin (CLD) in 1st-line AOC patients. Due to the lack of published phase II data on the CLD schedule, safety and activity analyses were planned within the trial. The former, previously reported for the first 50 patients treated with CLD, showed mild haematological toxicity, while non-hematological events seldom were higher than grade 2. Methods: AOC patients with AOC (stage IC-IV), aged =75, ECOG PS =2, are randomized to CP (carboplatin AUC 5 / paclitaxel 175 mg/m2, d1q21) or to CLD (carboplatin AUC 5 + Stealth liposomal doxorubicin 30 mg/m2, d1q21), both treatments for 6 cycles. According to a phase 2 design with p0=30%, p1=50%, alfa=0.10, 50 patients with measurable target lesions as defined by RECIST criteria were required and ≥20 responses had to be observed in order to define that the experimental schedule was sufficiently active to warrant phase III continuation. Results: Out of the first 137 patients randomly assigned to CLD, 87 were not eligible for response assessment by RECIST (35 had only non target lesions; 28 had only Ca 125 increased; 23 had no lesion and normal Ca 125; 1 never started treatment). Out the 50 patients eligible for response assessment, overall 34 responses were recorded (14 complete, 20 partial) for a response rate of 68% (95% CI: 53.3–80.5). In addition, among 35 patients with all non-target lesions 9 (26%) complete responses and 18 (51%) nonCR- nonPD were observed. In the remaining 28 patients evaluable only for Ca 125, this normalized in 96% of the cases at the end of the 6 cycles. Conclusions: An a priori planned activity analysis showed that CLD every 3 weeks is feasible and active in AOC patients suboptimally debulked and with measurable lesions. The trial is ongoing; as of December 28th, 2006, 615 patients have been enrolled out of 810 planned. No significant financial relationships to disclose.