Efficacy of pegylated liposomal doxorubicin (PLD) and oxaliplatin (OX) in pre-treated advanced epithelial ovarian cancer (EOC) and relation to p53 status.

15054 Background: The efficacy of PLD+Ox in pre-treated advanced EOC in third and fourth line suggests that the elevated survival in these patients might activate the p53 pathway.,Inclusion criteria: Performance Status≤2, relapse or progression after 1-3 lines of therapy; ≤4 prior antiblastic drugs; life expectancy >3 months; LVEF >50%.Treatment consisted of 1 hr infusion of PLD 30-35 mg/m on day 1 and 70 mg/m of Ox in 2 hrs on day 2 for 8 cycles, then 2 cycles of PLD alone. Clinical response was evaluated by CT scan every 3 cycles. Primary endpoints were overall survival and its correlation with p53.,From June 2000, 65 pre-treated pts were enrolled. They were divided according to platinum sensitivity into sens, part-sens and res (time to progression after platinum therapy of ≥12, ≥6 or <6 months). Median age = 65 yrs, range 41-84, (23 pts >70 yrs). 56 pts were evaluable for response: 28 sens with an ORR = 79%, 15 part-sens ORR = 47%, and 12 res ORR = 50%. 445 cycles were administered (median = 6 cycles/pt). Median survival from 1 cycle was 19 months, 10 and 8 months in sens and part-sens and res groups respectively (p = 0.00021). Major (G3-4) toxicities were: neutropenia (6 episodes), gastrointestinal (3 episodes). G1-2 neurosensorial toxicity was seen in 18 pts and PPE in 10 pts. 1 toxic-related death was recorded. Median LVEF showed no significant changes during treatment. There is no clear correlation between OS and amount of Platinum/Taxol administered previously. p53 was analyzed for expression and mutations. Mutations were sought in exons 5, 6, 7 and 8. Immunohistochemistry of 11 amplified samples showed p53 overexpression in 8 pts, of these 7/11 had a CR and/or PR (64%). The analysis is ongoing. The 5-yr survival after first relapse is 64%, 24% and 0% for sens, part-sens and res respectively. 6/6 (100%) evaluable patients with BRCA mutations responded to therapy (5 BRCA1 pts, 1 BRCA2 pt): 4 CR and 2 PR, presently all living.,The therapy is effective in increasing OS in Platinum-sensitive patients after re-exposure to Carboplatin and Taxol and may be effective in p53+/mutated pts and for pts with BRCA mutation. For Pt-refractory and Pt-partially-sensitive pts an optimized use of this treatment must be identified. No significant financial relationships to disclose.