5538 Background: Nasopharyngeal carcinoma (NPC) is a chemo-sensitive disease but there is yet no consensus on the best regimen for recurrent or metastatic diseases. Pemetrexed is a new agent with good efficacy and toxicity profiles in other cancers. This phase II study aims to evaluate its use in combination with cisplatin for NPC. METHODS Patients (pts) with metastatic or extensive recurrence (unsuitable for radical surgery or re-irradiation) were included. All had prior treatment with platinum-based chemotherapy. The regimen consisted of pemetrexed 500mg/m2 (with vitamin B12 and folic acid support) and cisplatin 75mg/m2 every 3 weeks. Assessments of efficacy were based on both radiological and biochemical (DNA copies of Epstein-Barr virus) response. Toxicity profile was assessed by both acute toxicity rates and quality of life (QOL) scores (measured with FACT-H&N version 4). Patients with response/stable disease and good tolerance were given another 2-4 cycles. RESULTS Fourteen pts (5 with loco-regional recurrences and 9 with metastases) were treated with this regimen; their median age was 51 (range, 39-68) years. All except one pts had elevated EBV-DNA (median, 34,750 copies/ml; range, 42-17,500,000). A total of 4-8 (median, 6) cycles had been given. Reduction of EBV-DNA copies by >=50% was observed in 12/13 (92%) pts, 2/13 (15%) pts even achieved biochemical complete remission (CR). Radiological assessment showed that one (7%) pt achieved CR, 2 (14%) had partial remission and 7 (50%) had stable diseases. The median time to progression was 30 weeks (range, 11-119 weeks). Only one pt (7%) developed grade 4 toxicity (anemia). The most common grade 3 toxicities were neutropenia (29%) and anemia (21%). All 14 pts had QOL assessment at baseline and after the fourth cycle; 12 (86%) pts had further assessment after the sixth cycle. No significant deterioration in QOL was observed: the total QOL scores (mean) changed from 99 at baseline to 95 after the fourth cycle (p=0.35) and 90 after the sixth cycle (p=0.16). CONCLUSIONS Cisplatin-pemetrexed was a well tolerated regimen and the efficacy for metastatic/recurrent NPC was encouraging. Further evaluation of its role in treatment of NPC is warranted.