5028 Background: Patients (pts) with high risk gestational trophoblastic neoplasia (GTN) or who fail low risk single agent chemotherapy (CT) require multi agent CT to be cured. The most common regimen is etoposide (E), methotrexate and actinomycin D (A) alternating weekly with cyclophophamide and vincristine (EMA/CO). Cisplatin (P) is a very active drug but its role is controversial and usually restricted to second line. We report results of a platinum based therapy: APE. Methods: We evaluated the efficacy and safety on 103 pts treated at Institut Gustave Roussy (IGR) (n=80) or other French centers (n=23) between 1983 and 2010 with APE for high risk GTN (defined by IGR criteria [Azab, Cancer, 1988] and/or FIGO score >6). Pts with brain metastasis were excluded. Results: Efficacy was evaluated on 59 pts treated for high risk GTN in first line, and on 39 pts in >2nd line including 13 pts after multi agent CT. We excluded pts with placental site trophoblastic tumors (n=2), or with FIGO score <7 and without IGR criteria (n=3). Complete remission (CR) rate was 95%. Seven pts (7 %) relapsed and a second CR was obtained for all with surgery and/or CT. Only one patient died due to GTN, after successive CRs obtained with 3 regimens. Five year overall survival (median follow-up 6.6 years) was 98%. Toxicity was evaluated on 95 pts. No toxic death occurred. Given good efficacy and to avoid acute hematotoxicity and long-term G>1 neuro and ototoxicity APE regimen was modified as detailed in the Table (below). Long-term neuro (5 pts, G1), oto (2 pts, G1 and 2 pts, G2) and renal toxicities (1 pt, G1 ) were recorded. No long-term G2 toxicities were observed with APE3. One pt developed an AML 4 after 4cy APE and 6 cy EMA/CO. 37 pts of 40 who wished to be pregnant succeeded and all of them had at least one live birth. Conclusions: With a 98% long-term overall survival rate, an excellent reproductive outcome, and no detectable long-term toxicity, APE-3 should be regarded as an alternative standard option to EMA/CO for high-risk GTN. [Table: see text]