Phase II trial of oxaliplatin (OXA) combined with paclitaxel (P) as first-line chemotherapy for patients (pts) with advanced ovarian cancer (AOC): Preliminary results

Abstract

5075 Background: Despite the introduction of paclitaxel/platinum combinations in first line treatment of AOC, a small proportion of patients fail to respond. This has been linked to genetic or epigenetic deficiency in activity in mismatch repair (MMR; MLH1, MSH2). OXA has activity in MMR deficient cells and the OXA/ P combination has been shown to be safe and highly active in pre-treated AOC pts (Faivre et al. Ann Oncol 10:1125, 1999). This motivated the present phase II study in first line AOC. Methods: AOC pts with histologically proven stage IIc or IIIa-c after maximal debulking surgery (microscopic disease or macroscopic disease ≤2 cm) performed 2–7 weeks before study treatment start, received 175 mg/m2 P, 3-hour intravenous infusion, followed by 130 mg/m2 OXA, 2-hour intravenous infusion, every 3 weeks, on an outpatient basis, without G-CSF. A maximum of 6 cycles were administered before evaluation by second look laparoscopy or laparotomy. Pts with positive histology after second look surgery could receive up to 2 further cycles; pts with pathological complete response received no further treatment. Results: Between Aug 2001 and Jan 2003, 17 pts were entered in 9 centres (49 planned), 14 eligible, 3 ineligible (2 colorectal cancer with peritoneal presentation, 1 pre-treated with OXA/cisplatin/P). Median age 59 years (range 40–68); Performance status 0/1/2: 10/3/1; histology serous: 11, other: 3; FIGO stage IIIb: 5, IIIc: 9; microscopic residual disease: 3, macroscopic: 11. Patients received a median of 6 cycles (6–8). Efficacy: Of 13 pts evaluable for pathological response, 8 had complete response (62%) and 5 stable disease. With a median follow-up of 14 months (6–24), only 2 pts with macroscopic residual disease progressed. Median PFS: 14 months (5–22), 9 out of 12 patients have an ongoing PFS >12 months. Safety (NCI-CTC; 91 cycles) % by pts: neutropenia grade (Gr) 3/4: 7%/14%; febrile neutropenia: 7%, reversible neurosensory toxicity (OXA specific scale) ≥Gr2: 21%. Conclusion: The OXA/P combination shows high antitumor activity and a safe toxicity profile in first-line treatment for AOC. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration MGI Pharma, Inc. Sanofi