Phase II trial of oxaliplatin (OXA) combined with paclitaxel (P) inplatinum + taxanes sensitive advanced ovarian cancer (AOC) patients: Final results

Abstract

5023 Background: OXA is active in mismatch repair (MMR) deficient cells, a condition prevalent in pretreated AOC. OXA/P shows high activity in investigator initiated studies (Faivre et al, Ann Oncol 10:1125, 1999). We evaluated efficacy and safety of OXA/P in AOC pts with clinically evaluable disease pretreated with 1 platinum based regimen ± taxanes and a progression-platinum-free interval (PPFI) ≥6 months (mo). Methods: From Dec 99 to Apr 02, 105 pts, 14 centres received P 175 mg/m2, 3h iv followed by OXA 130 mg/m2, 2h iv, every 3 weeks, for up to 9 cycles (cy) without G-CSF. Median (m) age: 58 years (range 37–83), 96% PS 0/1. PPFI: 69 pts >12 mo, 34 pts 6–12 mo; 80 pts (76%) taxane-pretreated. Results: 708 cy administered; m 7 cy/pt (1–9). Relative dose intensity: OXA 0.95, P 0.97. Efficacy: 98 pts eligible, 7 non-eligible (3 bowel occlusion, 3 >1 prior platinum-based chemotherapy, 2 PPFI not determinable). 98 pts evaluable for response (see table) ORR: 81% (95%CI 71–88), all but 3 responses third party reviewed; 90 pts evaluable for biological response (baseline CA125 ≥50 UI/ml): 89% response (decrease >75% or CA125 normalization >1 mo). Combined RECIST /biological response: 88% (95%CI 80–94). M follow-up: 27 mo (14–48); m PFS: 10.2 mo; projected OS >28 mo (44 events). Safety (NCI-CTC); % pts with grade (gr) 3/4: neutropenia 21/46; thrombocytopenia 15/1; nausea-vomiting 9/2; asthenia 7/1; allergic reaction: 1/1; cumulative reversible neurotoxicity gr 2/3 (OXA specific scale): 50/25 after a m 7 cy (3–9); febrile neutropenia: 9 episodes/8 pts; 4% cy required G-CSF; no treatment-related deaths. Conclusion: The OXA/P combination shows the highest level of efficacy in platinum-sensitive third party reviewed large phase II studies in platinum/taxane pretreated AOC pts with PPFI >6 mo, and can be administered in an outpatient setting without special safety measures. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration MGI Pharma, Inc.