Pemetrexed, a multitarget antifolate which inhibits thymidylate synthase, dihydrofolate reductase and glycinamide ribonucleotide formyltransferase, was approved for the treatment of lung cancer and mesothelioma. In addition to its therapeutic efficacy, pemetrexed has tolerable safety profile and is considered as important therapeutic option for patients of poor performance statue or older age. Pemetrexed was studied in combination with gemcitabine in BTC patients and needs further research in BTC patients. Erlotinib is EGFR tyrosine kinase inhibitor. In BTC and pancreatic cancer, erlotinib showed prolonged survival in combination with chemotherapy. Moreover, the addition of erlotinib to gemcitabine and oxaliplatin showed antitumour activity in our previous phase III trial. And combination of pemetrexed and erlotinib showed tolerable safety profile in lung cancer trial.