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

Abstract

5014 Background: The MITO-2 (Multicentre Italian Trials in Ovarian cancer) study is a randomized phase III study comparing CP to CLD in 1st-line AOC patients (pts). Due to the lack of published phase II data on the CLD schedule, an early safety analysis had been planned. Methods: Pts 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. Primary objective of the trial is progression-free survival. Toxicity is coded according to the NCI-CTC, v2.0 and is reported as percent of pts. Results: A preliminary analysis of safety, planned a priori, was performed as of July 2004 and is reported here. Data were available for 96 pts (49 CP and 47 CLD). Median age (range) was 56 (34–75). PS was 0, 1, 2 in 59, 32, 5 pts, respectively. 49 pts were optimally debulked. In the CLD arm, 87% of the pts completed the 6 cycles (86% with CP). No toxic deaths were recorded in CLD arm (1 toxic death in CP). As for hematological toxicity, G3 anemia was reported in 17% (CP 10%), G3/4 neutropenia in 34%/11% (CP 24%/24%), G3/4 thrombocytopenia in 19%/4% (CP 10%/-). Allergy was reported in 6 CLD pts and in 4 CP pts. Organ toxicity was not frequent with CLD: pulmonary 4% G1, heart rhythm 6% G1, hepatic 6% G1, 4% G2 and 2% G3. Complete hair loss was observed in 4% of pts with CLD and 81% with CP. Neuropathy was G1 in 1 pt with CLD while it was G1 in 33% and G2 in 8% with CP. Palmar-plantar erythrodysesthesia was recorded in 15% with CLD (13% G1, 2% G2). Conclusions: A planned safety analysis showed that CLD every 3 weeks is feasible in AOC pts. Safety profile of CLD seems different from CP, with markedly less neurotoxicity and hair loss, and higher incidence of mild skin toxicity. The trial is ongoing; as of December 2nd, 2004, 196 patients have been enrolled. No significant financial relationships to disclose.