Recent advances for the treatment of pancreatic and biliary tract cancer after first-line treatment failure

References

• Cardinale V, Wang Y, Carpino G, et al. The biliary tree-a reservoir of multipotent stem cells. Nat Rev Gastroenterol Hepatol 2012;9:231-40
   PubMed Web of Science ®Google Scholar
• Hidalgo M. Pancreatic Cancer. N Eng J Med 2010;362:1605-17
   PubMed Web of Science ®Google Scholar
• Artinyan A, Soriano PA, Prendergast C, et al. The anatomic location of pancreatic cancer is a prognostic factor for survival. HPB (Oxford) 2008;10:371-6
   PubMed Web of Science ®Google Scholar
• Evans DB, Varadhachary GR, Crane CH, et al. Preoperative gemcitabine-based chemoradiation for patients with resectable adenocarcinoma of the pancreatic head. J Clin Oncol 2008;26:3496-502
   PubMed Web of Science ®Google Scholar
• Neoptolemos JP, Stocken DD, Friess H, et al. A randomized trial of chemoradiotherapy and chemotherapy after resection of pancreatic cancer. N Engl J Med 2004;350:1200-10
   PubMed Web of Science ®Google Scholar
• Fukutomi A, Uesaka K, Boku N, et al. JASPAC 01: Randomized phase III trial of adjuvant chemotherapy with gemcitabine versus S-1 for patients with resected pancreatic cancer. J Clin Oncol 2013;31:suppl;abstr4008
   PubMed Web of Science ®Google Scholar
• Hammel P, Huguet F, Van Laethem JL, et al. Comparison of chemoradiotherapy (CRT) and chemotherapy (CT) in patients with a locally advanced pancreatic cancer (LAPC) controlled after 4 months of gemcitabine with or without erlotinib: Final results of the international phase III LAP 07 study. J Clin Oncol 2013;31:suppl; abstr LBA4003
   Google Scholar
• Burris HA, Moore MJ, Andersen J, et al. Improvements in survival and clinical benefit with gemcitabine as first-line therapy for patients with advanced pancreas cancer: a randomized trial. J Clin Oncol 1997;15:2403-13
   PubMed Web of Science ®Google Scholar
• Ueno H, Ioka T, Ikeda M, et al. Randomized phase III study of gemcitabine plus S-1, S-1 alone, or gemcitabine alone in patients with locally advanced and metastatic pancreatic cancer in Japan and Taiwan: GEST study. J Clin Oncol 2013;31:1640-8
   PubMed Web of Science ®Google Scholar
• Chuah B, Goh BC, Lee SC, et al. Comparison of the pharmacokinetics and pharmacodynamics of S-1 between Caucasian and East Asian patients. Cancer Sci 102:478-83.2011
   PubMed Web of Science ®Google Scholar
• Conroy T, Desseigne F, Ychou M, et al. FOLFIRINOX versus gemcitabine for metastatic pancreatic cancer. N Eng J Med 2011;364:1817-25
   PubMed Web of Science ®Google Scholar
• Von Hoff DD, Ervin T, Arena FP, et al. Increased survival in pancreatic cancer with nab-paclitaxel plus gemcitabine. N Eng J Med 2013;369:1691-703
   PubMed Web of Science ®Google Scholar
• Moore MJ, Goldstein D, Hamm J, et al.Figer A. Erlotinib plus gemcitabine compared with gemcitabine alone in patients with advanced pancreatic cancer. A phase III trial of the national cancer institute of canada clinical trials group. J Clin Oncol 2007;25:1960-6
   PubMed Web of Science ®Google Scholar
• Burris HA, Rivkin S, Reynolds R, et al. Phase II trial of oral rubitecan in previously treated pancreatic cancer patients. Oncologist 2005;10:183-90
   PubMed Web of Science ®Google Scholar
• Androulakis N, Syrigos K, Polyzos A, et al. Oxaliplatin for pretreated patients with advanced or metastatic pancreatic cancer: a multicenter phase II study. Cancer Invest 2005;23:9-12
   PubMed Web of Science ®Google Scholar
• Boeck S, Weigang-Köler K, Fuchs M, et al. Second-line chemotherapy with pemetrexed after gemcitabine failure in patients with advanced pancreatic cancer: a multicenter Phase II trial. Ann Oncol 2007;18:745-51
   PubMed Web of Science ®Google Scholar
• Boeck S, Wilkowski R, Bruns CJ, et al. Oral capecitabine in gemcitabine-pretreated patients with advanced pancreatic cancer. Oncology 2007;73:221-7
   PubMed Web of Science ®Google Scholar
• Yi SY, Park YS, Kim HS, et al. Irinotecan monotherapy as second-line treatment in advanced pancreatic cancer. Cancer Chemother Pharmacol 2009;63:1141-5
   PubMed Web of Science ®Google Scholar
• Takahara N, Nakai Y, Isayama H, et al. Uridine diphosphate glucuronosyltransferase 1 familypolypeptide A1 gene (UGT1A1) polymorphism are associated with toxicity and efficacy in Irinotecan monotherapy for refractory pancreatic cancer. Cancer Chemother Pharmacol 2013;71:85-92
   PubMed Web of Science ®Google Scholar
• Ko AH, Tempero MA, Shan YS, et al. A multinational phase 2 study of nanoliposomal irinotecan sucrosofate (PEP02, MM-398) for patients with gemcitabine-refractory metastatic pancreatic cancer. Br J Cancer 2013;109:920-5
   PubMed Web of Science ®Google Scholar
• Saif MW, Syrigos K, Penney R, et al. Docetaxel second ine therapy in patients with advanced pancreatic cancer: a retrospective study. Anticancer Res 2010;30:2905-9
   PubMed Web of Science ®Google Scholar
• Maeda S, Motoi F, Onogawa T, et al. Paclitaxel as second-line chemotherapy in patients with gemcitabine-refractory pancreatic cancer: a retrospective study. Int J Clin Oncol 2011;16:539-45
   PubMed Web of Science ®Google Scholar
• Peddi PF, Cho M, Wang J, et al. Nab-paclitaxel monotherapy in refractory pancreatic adenocarcinoma. J Gastrointest Oncol 2013;4:370-3
   PubMedGoogle Scholar
• Hosein PJ, De Lima Lopes G, Pastorini VH, et al. A phase II trial of nab-paclitaxel as second-line therapy in patients with advanced pancreatic cancer. Am J Clin Oncol 2013;36:151-6
   PubMed Web of Science ®Google Scholar
• Li D, Pant S, Ryan DP, et al. A phase II, open-label, multicenter study to evaluate the antitumor efficacy of CO-1.01 as second-line therapy for gemcitabine-refractory patients with stage IV pancreatic adenocarcinoma and negative tumor hENT1 expression. Pancreatology 2014;14:398-402
   PubMed Web of Science ®Google Scholar
• Morizane C, Okusaka T, Furuse J, et al. A phase II study of S-1 in gemcitabine-refractory metastatic pancreatic cancer. Cancer Chemother Pharmacol 2009;63:313-19
   PubMed Web of Science ®Google Scholar
• Todaka A, Fukutomi A, Boku N, et al. S-1 monotherapy as second line treatment for advanced pancreatic cancer after gemcitabine failure. Jpn J Clin Oncol 2010;40:567-72
   PubMed Web of Science ®Google Scholar
• Sudo K, Yamaguchi T, Nakamura K, et al. Phase II study of S-1 in patients with gemcitabine-resistant advanced pancreatic cancer. Cancer Chemother Pharmacol 2011;67:249-54
   PubMed Web of Science ®Google Scholar
• Kozuch P, Grossbard ML, Barzdins A, et al. Irinotecan combined with gemcitabine, 5-fluorouracil, leucovorin, and cisplatin (G-FLIP) is an effective and non cross resistant treatment for chemotherapy refractory metastatic pancreatic cancer. Oncologist 2001;6:488-95
   PubMed Web of Science ®Google Scholar
• Reni M, Cereda S, Mazza E, et al. PEFG (cisplatin, epirubicin, 5-fluorouracil, gemcitabine) regimen as second-line therapy in patients with progressive or recurrent pancreatic cancer after gemcitabine-containing chemotherapy. Am J Clin Oncol 2008;31:145-50
   PubMed Web of Science ®Google Scholar
• Demols A, Peeters M, Polus M, et al. Gemcitabine and oxaliplatin (GEMOX) in gemcitabine refractory advanced pancreatic adenocarcinoma: a phase II study. Br J Cancer 2006;94:481-5
   PubMed Web of Science ®Google Scholar
• Morizane C, Okusaka T, Ueno H, et al. Phase I/II study of gemcitabine as a fixed dose rate infusion and S1 combination therapy (FGS) in gemcitabine-refractory advanced pancreatic cancer. Cancer Chemother Pharmacol 2012;69:957-64
   PubMed Web of Science ®Google Scholar
• Tschoep-Lechner KE, Milani V, Berger F, et al. Gemcitabine and cisplatin combined with regional hyperthermia as second-line treatment in patients with gemcitabine-refractory advanced pancreatic cancer. Int J Hyperthermia 2013;29:8-16
   PubMed Web of Science ®Google Scholar
• Stathopoulos GP, Boulikas T, Vougiouka M, et al. Liposomal cisplatin combined with gemcitabine in pretreated advanced pancreatic cancer patients: a phase I-II study. Oncol Rep 2006;15:1201-4
   PubMed Web of Science ®Google Scholar
• Giordano G, Milella M, Melisi D, et al. Nab-paclitaxel and gemcitabine in pretreated advanced pancreatic cancer patients: A multicentre retrospective analysis. Abs. ESMO 2014;718P
   Google Scholar
• Lim KH, Han SW, Oh DY, et al. Outcome of infusion 5-fluorouracil, doxorubicin, and mitomycin-C (iFAM) chemotherapy and analysis of prognostic factors in patients with refractory advanced biliary tract cancer. Oncology 2012;83:57-66
   PubMed Web of Science ®Google Scholar
• Lee S, Oh SY, Kim BG, et al. Second-line treatment with a combination of continuous 5-fluorouracil, doxorubicin, and mitomycin-C (conti-FAM) in gemcitabine-pretreated pancreatic and biliary tract cancer. Am J Clin Oncol 2009;32:348-52
   PubMed Web of Science ®Google Scholar
• Takahara N, Isayama H, Nakai Y, et al. A retrospective study of study of S-1 and oxaliplatin combination chemotherapy in patients with refractory pancreatic cancer. Cancer Chemother Pharmacol 2013;72:985-90
   PubMed Web of Science ®Google Scholar
• Pelzer U, Stieler J, Roll L, et al. Second-line therapy i refractory pancreatic cancer: results of a phase II study. Onkologie 2009;32:99-102
   PubMed Web of Science ®Google Scholar
• Novarino A, Satolli MA, Chiappino I, et al. Oxaliplatin, 5-fluorouracil, and leucovorin as second-line treatment for advanced pancreatic cancer. Am J Clin Oncol 2009;32:44-8
   PubMed Web of Science ®Google Scholar
• Chung JW, Jang HW, Chung MJ, et al. Folfox4 as a rescue chemotherapy for gemcitabine-refrectory pancreatic cancer. Hepatogastroenterology 2013;60:363-7
   PubMed Web of Science ®Google Scholar
• Xiong HQ, Varadhachary GR, Blais JC, et al. Phase 2 trial of oxaliplatin plus capecitabine (XELOX) as second-line therapy for patients with advanced pancreatic cancer. Cancer 2008;113:2046-52
   PubMed Web of Science ®Google Scholar
• Berk V, Ozdemir N, Ozkan M, et al. XELOX vs. FOLFOX4 as second-line chemotherapy in advanced pancreatic cancer. Hepatogastroenterology 2012;59:2635-9
   PubMed Web of Science ®Google Scholar
• Gebbia V, Maiello E, Giuliani F, et al. Irinotecan plus bolus/infusional 5-Fluorouracil and leucovorin in patients with pretreated advanced pancreatic carcinoma: a multicenter experience of the Gruppo Oncologico Italia Meridionale. Am J Clin Oncol 2010;33:461-4
   PubMed Web of Science ®Google Scholar
• Zaniboni A, Aitini E, Barni S, et al. FOLFIRI as second-line chemotherapy for advanced pancreatic cancer: a GISCAD multi center phase II study. Cancer Chemother Pharmacol 2012;69:1641-5
   PubMed Web of Science ®Google Scholar
• Neuzillet C, Hentic O, Rousseau B, et al. FOLFIRI regimen in metastatic pancreatic adenocarcinoma resistant to gemctabine and platinum-salts. World J Gastroenterol 2012;18:4533-41
   PubMed Web of Science ®Google Scholar
• Cereda S, Reni M, Rognone A, et al. XELIRI or FOLFIRI as salvage therapy in advanced pancreatic cancer. Anticancer Res 2010;30:4785-90
   PubMed Web of Science ®Google Scholar
• Assaf E, Verlinde-Carvalho M, Delbaldo C, et al. 5-fluorouracil/leucovorin combined with irinotecan and oxaliplatin (FOLFIRINOX) as second-line chemotherapy in patients with metastatic pancreatic adenocarcinoma. Oncology 2011;80:301-6
   PubMed Web of Science ®Google Scholar
• Kim YJ, Bang S, Park JY, et al. Phase II study of 5-fluorouracil and paclitaxel in patients with gemcitabine refractory pancreatic cancer. Cancer Chemother Pharmacol 2009;63:529-33
   PubMed Web of Science ®Google Scholar
• Katapodis O, Polyzos A, Kentepozidis N, et al. Second-line chemotherapy with capecitabine (Xeloda) and docetaxel (Taxotere) in previously treated, unresectable adenocarcinoma of pancreas: the final results of a phase II trial. Cancer Chemother Pharmacol 2011;67:361-8
   PubMed Web of Science ®Google Scholar
• Shi SB, Wang M, Niu ZX, et al. Phase II trial of capecitabine combined with thalidomide in second-line treatment of advanced pancreatic cancer. Pancreatology 2012;12:475-9
   PubMed Web of Science ®Google Scholar
• Pino MS, Milella M, Gelibter A, et al. Capecitabine and celecoxib as second-line treatment of advanced pancreatic and biliary tract cancers. Oncology 2009;76:254-61
   PubMed Web of Science ®Google Scholar
• Cereda S, Reni M, Rognone A, et al. Salvage therapy with mitomycin and ifosfamide in patients with gemcitabine-resistant metastatic pancreatic cancer: a phase II trial. Chemotherapy 2011;57:156-61
   PubMed Web of Science ®Google Scholar
• Reni M, Pasetto L, Aprile G, et al. Raltitrexed-eloxatin salvage chemotherapy in gemcitabine-resistant metastatic pancreatic cancer. Br J Cancer 2006;94:785-91
   PubMed Web of Science ®Google Scholar
• Cantore M, Rabbi C, Fiorentini G, et al. Combined irinotecan and oxaliplatin in patents with advanced pretreated pancreatic cancer. Oncology 2004;67:93-7
   PubMed Web of Science ®Google Scholar
• Pelzer U, Schwaner I, Stieler J, et al. Best supportive care (BSC) versus oxaliplatin, folinic acid and 5-fluorouracil (OFF) plus BSC in patients for second-line advanced pancreatic cancer: a phase III-study from the German CONKO-study group. Eur J Cancer 2011;47:1676-81
   PubMed Web of Science ®Google Scholar
• Oettle H, Riess H, Stieler JM, et al. Second-line oxaliplatin, folinic acid, and fluorouracil versus folinic acid and fluorouracil alone for gemcitabine-refractory pancreatic cancer: outcomes from the CONKO-003 trial. J Clin Oncol 2014;32:2423-9
   PubMed Web of Science ®Google Scholar
• Yoo C, Hwang JY, Kim JE, et al. A randomized phase II study of modified FOLFIRI 3 vs modified FOLFOX as second-line therapy in patients with gemcitabine-refractory advanced pancreatic cancer. Br J Cancer 2009;101:1658-63
   PubMed Web of Science ®Google Scholar
• Azmy A, Abdelwahab S, Yassen M. Oxaliplatin and bolus-modulated 5-fluorouracil as a second-line treatment or advanced pancreatic cancer: can bolus regimens replace FOLFOX when considered for second line? ISRN Oncol 2013;2013:358538
   Google Scholar
• Ulrich-Pur H, Raderer M, Verena Kornek G, et al. Irinotecan plus raltitrexed vs raltitrexed alone in patients with gemcitabine-pretreated advanced pancreatic adenocarcinoma. Br J Cancer 2003;88:1180-4
   PubMed Web of Science ®Google Scholar
• Ohkawa S, Okusaka T, Isayama H, et al. Randomised phase II trial of S-1 plus oxaliplatin vs S-1 in patients with gemcitabine-refractory pancreatic cancer. Br J Cancer 2015;112:1428-34
   PubMed Web of Science ®Google Scholar
• Ge F, Xu N, Bai Y, et al. S-1 as monotherapy or in combination with leucovorin as second-line treatment in gemcitabine-refractory advanced pancreatic cancer: a randomized, open label, multicenter, phase II study. Oncologist 2014;19:1133-4
   PubMed Web of Science ®Google Scholar
• Ciuleanu TE, Pavlovsky AV, Bodoky G, et al. A randomized phase III trial of glufosfamide compared with best supportive care in metastatic pancreatic adenocarcinoma previously treated with gemcitabine. Eur J Cancer 2009;45:1589-96
   PubMed Web of Science ®Google Scholar
• Chen LT, Von Hoff DD, Li CP, et al. Expanded analysis of napoli-1: phase III study of MM-398 (nal-IRI), with or without 5-fluorouracil and leucovorin, versus 5-fluorouracil and leucovorin in metastatic pancreatic cancer (mPAC) previously treated with gemcitabine-based therapy. J Clin Oncol 2015;33:suppl3;abstr234
   Google Scholar
• Warsame R, Grothey A. Treatment option for advanced pancreatic cancer: a review. Exp Rev Anticancer Ther 2012;12:1327-36
   PubMed Web of Science ®Google Scholar
• Study of gemcitabine and Abraxane for pancreas cancer. Available from: https://clinicaltrials.gov/ct2/show/NCT02242409
   Google Scholar
• Ignatiadis M, Polyzos A, Stathopoulos GP, et al. A multicenter phase II study of docetaxel in combination with gefitinib in gemcitabine-pretreated patients with advanced/metastatic pancreatic cancer. Oncology 2006;71:159-63
   PubMed Web of Science ®Google Scholar
• Brell JM, Matin K, Evans T, et al. Phase II study of docetaxel and gefitinib as second-line therapy in gemcitabine pretreated patients with advanced pancreatic cancer. Oncology 2009;76:270-4
   PubMed Web of Science ®Google Scholar
• Renouf DJ, Tang PA, Hedley D, et al. A phase II study of erlotinib in gemcitabine refractory advanced pancreatic cancer. Eur J Cancer 2014;50:1909-15
   PubMed Web of Science ®Google Scholar
• Propper D, Davidenko I, Bridgewater J, et al. Phase II, randomized, biomarker identification trial (MARK) for erlotinib in patients with advanced pancreatic carcinoma. Ann Oncol 2014;25:1384-90
   PubMed Web of Science ®Google Scholar
• Kulke MH, Blaszkowsky LS, Ryan DP, et al. Capecitabine plus erlotinib in gemcitabine refractory advanced pancreatic cancer. J Clin Oncol 2007;25:4787-92
   PubMed Web of Science ®Google Scholar
• Ko AH, Venook AP, Bergsland EK, et al. A phase II study of bevacizumab plus erlotinib for gemcitabine-refractory metastatic pancreatic cancer. Cancer Chemother Pharmacol 2010;66:1051-7
   PubMed Web of Science ®Google Scholar
• Javle M, Shroff RT, Xiong H, et al. Inhibition of the mammalian target of rapamycin (mTOR) in advanced pancreatic cancer: results of two phase II studies. BMC Cancer 2010;10:368
   PubMed Web of Science ®Google Scholar
• Wolpin BM, Hezel AF, Abrams T, et al. Oral mTOR inhibitor everolimus in patients with gemcitabine-refractory metastatic pancreatic cancer. J Clin Oncol 2009;27:193-8
   PubMed Web of Science ®Google Scholar
• Kordes S, Klümpen HJ, Waterman MJ, et al. Phase II study of capecitabine and the oral mTOR inhibitor everolimus in patients with advanced pancreatic cancer. Cancer Chemother Pharmacol 2015;75:1135-41
   PubMed Web of Science ®Google Scholar
• O’Reilly EM, Niedzwiecki D, Hall M, et al. A Cancer and Leukemia Group B phase II study of sunitinib malate in patients with previously treated metastatic pancreatic adenocarcinoma (CALGB 80603). Oncologist 2010;15:1310-19
   PubMed Web of Science ®Google Scholar
• Astsaturov IA, Meropol NJ, Alpaugh RK, et al. Phase II and coagulation cascade biomarker study of bevacizumab with or without docetaxel in patients with previously treated metastatic pancreatic adenocarcinoma. Am J Clin Oncol 2011;34:70-5
   PubMed Web of Science ®Google Scholar
• Bodoky G, Timcheva C, Spigel DR, et al. A phase II open-label randomized study to assess the efficacy and safety of selumetinib (AZD6244 [ARRY-142886]) versus capecitabine in patients with advanced or metastatic pancreatic cancer who have failed first-line gemcitabine therapy. Invest New Drugs 2012;30:1216-23
   PubMed Web of Science ®Google Scholar
• Starling N, Hawkes EA, Chau I, et al. A dose escalation study of gemcitabine plus oxaliplatin in combination with imatinib for gemcitabine-refractory advanced pancreatic adenocarcinoma. Ann Oncol 2012;23:942-7
   PubMed Web of Science ®Google Scholar
• Carvajal RD, Tse A, Shah MA, et al. A phase II study of flavopiridol (Alvocidib) in combination with docetaxel in refractory, metastatic pancreatic cancer. Pancreatology 2009;9:404-9
   PubMed Web of Science ®Google Scholar
• Bedard PL, Tabernero J, Janku FF, et al. A phase Ib dose-escalation study of the oral pan-PI3K inhibitor buparlisib (BKM120) in combination with the oral MEK1/2 inhibitor trametinib (GSK11202112) in patients with selected advanced solid tumors. Clin Cancer Res 2015;21:730-8
   PubMed Web of Science ®Google Scholar
• Le DT, Wang-Gillam A, Picozzi V, et al. Safety and survival with GVAX Pancreas Prime and listeria monocytogenes-expressing mesothelin (CRS-207) boost vaccine for metastatic pancreatic cancer. J Clin Oncol 2015;33:1325-33
   PubMed Web of Science ®Google Scholar
• Glufosfamide versus 5-FU in second line metastatic pancreatic cancer. Available from: https://www.clinicaltrials.gov/ct2/show/NCT01954992
   Google Scholar
• Randomized study with oxaliplatin in 2nd line pancreatic cancer. Available from: https://clinicaltrials.gov/ct2/show/NCT01121848
   Google Scholar
• Phase 3 Trial of 90Y-clivatuzumab tetraxetan & gemcitabine vs placebo & gemcitabine in metastatic pancreatic cancer (PANCRIT®-1). Available from: https://clinicaltrials.gov/ct2/show/NCT01956812
   Google Scholar
• Sasaki T, Isayama H, Nakai Y, et al. Improvement of prognosis for unresectable biliary tract cancer. World J Gastroenterol 2013;19:72-7
   PubMed Web of Science ®Google Scholar
• Horgan AM, Amir E, Walter T, et al. Adjuvant therapy of biliary tract cancer: a systemic review and meta-analysis. J Clin Oncol 2012;30:1934-40
   PubMed Web of Science ®Google Scholar
• Valle J, Wasan H, Palmer DH, et al. Cisplatin plus gemcitabine versus gemcitabine for biliary tract cancer. N Eng J Med 2010;362:1273-81
   PubMed Web of Science ®Google Scholar
• Sharma A, Dwary AD, Mohanti BK, et al. Best supportive care compared with chemotherapy for unresectable gall bladder cancer: a randomized controlled study. J Clin Oncol 2010;28:4581-6
   PubMed Web of Science ®Google Scholar
• Lee J, Park SH, Chang HM, et al. Gemcitabine and oxaliplatin with or without erlotinib in advanced biliary-tract cancer: a multicentre, open-label, randomised, phase-3 study. Lancet Oncol 2012;13:181-8
   PubMed Web of Science ®Google Scholar
• Malka D, Cervera P, Foulon S, et al. Gemcitabine and oxaliplatin with or without cetuximab in advanced biliary-tract cancer (BINGO): a randomised, open-label, non-comparative phase 2 trial. Lancet Oncol 2014;15:819-28
   PubMed Web of Science ®Google Scholar
• Romiti A, D’Antonio C, Zullo A, et al. Chemotherapy for the biliary tract cancers: moving toward improved survival time. J Gastrointest Cancer 2012;43:396-404
   PubMedGoogle Scholar
• Romiti A, Barucca V, Zullo A, et al. Tumours of ampulla of Vater: A case series and review of chemotherapy options. World J Gastrointest Oncol 2012;4:60-7
   PubMedGoogle Scholar
• Sasaki T, Isayama H, Nakai Y, et al. Feasibility study of gemcitabine and cisplatin combination chemotherapy for patients with refractory biliary tract cancer. Invest New Drugs 2011;29:1488-93
   PubMed Web of Science ®Google Scholar
• Oh SY, Jeong CY, Hong SC, et al. Phase II study of second line gemcitabine single chemotherapy for biliary tract cancer patients with 5-fluorouracil refractoriness. Invest New Drugs 2011;29:1066-72
   PubMed Web of Science ®Google Scholar
• Sasaki T, Isayama H, Nakai Y, et al. A pilot study of salvage irinotecan monotherapy for advanced biliary tract cancer. Anticancer Res 2013;33:2619-22
   PubMed Web of Science ®Google Scholar
• Sasaki T, Isayama H, Nakai Y, et al. Multicenter phase II study of S-1 monotherapy as second-line chemotherapy for advanced biliary tract cancer refractory to gemcitabine. Invest New Drugs 2012;30:708-13
   PubMed Web of Science ®Google Scholar
• Lim KH, Han SW, Oh DY, et al. Outcome of infusion 5-fluorouracil, doxorubicin, and mitomycin-C (iFAM) chemotherapy and analysis of prognostic factors in patients with refractory advanced biliary tract cancer. Oncology 2012;83:57-66
   PubMed Web of Science ®Google Scholar
• He S, Shen J, Sun X, et al. A phase II FOLFOX-4 regimen as second line treatment in advanced biliary tract cancer refractory to gemcitabine/cisplatin. J Chemother 2014;26:243-7
   PubMed Web of Science ®Google Scholar
• Hwang IG, Jang JS, Oh SY, et al. Phase II study of mFOLFOX3 (5-fluorouracil, leucovorin, oxaliplatin) as second-line treatment after gemcitabine failure in patients with unresectable/metastatic biliary tract cancer. Cancer Chemother Pharmacol 2015;75:757-62
   PubMed Web of Science ®Google Scholar
• Yi JH, Thongprasert S, Lee J, et al. A Phase II study of sunitinib as a second line treatment in advanced biliary tract carcinoma: a multicentre, multinational study. Eur J Cancer 2012;48:196-201
   PubMed Web of Science ®Google Scholar
• Bengala C, Bertolini F, Malavasi N, et al. Sorafenib in patients with advanced biliary tract carcinoma: a Phase II trial. Br J Cancer 2010;102:68-72
   PubMed Web of Science ®Google Scholar
• Buzzoni R, Pusceddu S, Bajetta E, et al. Activity and safety of RAD001 (everolimus) in patients affected by biliary tract cancer progressing after prior chemotherapy: a phase II I.T.M.O. group study. Ann Oncol 2014;25:1597-603
   PubMed Web of Science ®Google Scholar
• Philip PA, Mahoney MR, Allmer LC, et al. Phase II study of erlotinib in patients with advanced biliary cancer. J Clin Oncol 2006;24:3069-74
   PubMed Web of Science ®Google Scholar
• Rohrberg KS, Olesen RK, Pleiffer P, et al. Phase II trial of erlotinib and bevacizumab in patients with advanced upper gastrointestinal cancers. Acta Oncol 2012;51:234-42
   PubMed Web of Science ®Google Scholar
• Guion-Dusserre JF, Lorgis V, Vincent J, et al. FOLFIRI plus bevacizumab as a second-line therapy for metastatic intrahepatic cholangiocarcinoma. World J Gastroenterol 2015;21:2096-101
   PubMed Web of Science ®Google Scholar
• Paule B, Herelle MO, Rage E, et al. Cetuximab plus gemcitabine-oxaliplatin (GEMOX) in patients with refractory advanced intrahepatic cholangiocarcinomas. Oncology 2007;72:105-10
   PubMed Web of Science ®Google Scholar
• Bekaii-Saab T, Phelps MA, Li X, et al. Multi-institutional phase II study of selumetinib in patients with metastatic biliary cancers. J Clin Oncol 2011;29:2357-6
   PubMed Web of Science ®Google Scholar
• Ramanathan RK, Belani CP, Singh DA, et al. A phase II study of lapatinib in patients with advanced biliary tree and hepatocellular cancer. Cancer Chemother Pharmacol 2009;64:777-83
   PubMed Web of Science ®Google Scholar
• Walter T, Horgan AM, McNamara M, et al. Feasibility and benefits of second-line chemotherapy in advanced biliary tract cancer: a large retrospective study. Eur J Cancer 2013;49:329-35
   PubMed Web of Science ®Google Scholar
• Andersen JB, Thorgeirsson SS. A perspective on molecular therapy in cholangiocarcinoma: present status and future directions. Hepat Oncol 2014;1:143-57
   Google Scholar
• Yoshikawa D, Ojima H, Iwasaki M, et al. Clinicopathological and prognostic significance of EGFR, VEGF, and HER2 expression in cholangiocarcinoma. Br J Cancer 2008;98:418-25
   PubMed Web of Science ®Google Scholar
• Miyamoto M, Ojima H, Iwasaki M, et al. Prognostic significante of overexpression of c-MET oncoprotein in cholangiocarcinoma. Br J Cancer 2011;105:131-8
   PubMed Web of Science ®Google Scholar
• Romiti A, Cox MC, Sarcina I, et al. Metronomic chemotherapy for cancer treatment: a decade of clinical studies. Cancer Chemother Pharmacol 2013;72:13-33
   PubMed Web of Science ®Google Scholar
• Steinbild S, Arends J, Medinger M, et al. Metronomic antiangiogenetic therapy with capecitabine and celecoxib in advanced tumour patients-results of a phase II study. Onkologie 2007;30:629-35
   PubMed Web of Science ®Google Scholar
• Young SD, Whissel M, Noble JC, et al. Phase II clinical trial results involving treatment with low-dose daily oral cyclophosphamide, weekly vinblastine, and rofecoxib in patients with advanced solid tumours. Clin Cancer Res 2006;12:3092-8
   PubMed Web of Science ®Google Scholar
• Allegrini G, Desidero T, Barletta MT, et al. Clinical pharmacokinetic and pharmacodynamic evaluation of metronomic UFT and cyclophosphamide plus celecoxib in patients with advanced refractory gastrointestinal cancers. Angiogenesis 2012;15:275-86
   PubMed Web of Science ®Google Scholar
• Sun JF, Wu RR, Norris C, et al. Safety of chronic low-dose capecitabine as maintenance therapy in gastrointestinal cancers. Gastointest Cancer Res 2009;3:134-40
   PubMedGoogle Scholar
• Miger J, Holmqvist A, Sun XF, et al. Low-dose capecitabine (Xeloda) for treatment for gastrointestinal cancer. Med Oncol 2014;31:870
   PubMed Web of Science ®Google Scholar
• Romiti A, Onesti CE, Roberto M, et al. Continuous, low-dose capecitabine for patients with recurrent colorectal cancer. Med Oncol 2015;32:496
   Web of Science ®Google Scholar
• Study of ruxolitinib in pancreatic cancer patients (RECAP). Available from: https://clinicaltrials.gov/ct2/show/NCT01423604
   Google Scholar
• Selumetinib and Akt inhibitor MK2206 or mFOLFOX therapy comprising oxaliplatin and fluorouracil in treating patients with metastatic pancreatic cancer previously treated with chemotherapy. Available from: https://clinicaltrials.gov/ct2/show/NCT01658943
   Google Scholar
• A study of MEK162 and AMG 479 in patients with selected solid tumors. Available from: https://clinicaltrials.gov/ct2/show/NCT01562899
   Google Scholar
• Selumetinib and erlotinib hydrochloride in treating patients with locally advanced or metastatic pancreatic cancer. Available from: https://clinicaltrials.gov/ct2/show/NCT01222689
   Google Scholar
• Gemcitabine and pulse dose erlotinib in second line treatment of advanced pancreatic cancer. Available from: https://www.clinicaltrials.gov/ct2/show/NCT02154737
   Google Scholar
• Combination of irinotecan, oxaliplatin and cetuximab for locally advanced or metastatic pancreatic cancer. Available from: https://clinicaltrials.gov/ct2/show/NCT00871169
   Google Scholar
• Pilot trial of BMN 673, an oral PARP inhibitor, in patients with advanced solid tumors and deleterious BRCA mutations. Available from: https://clinicaltrials.gov/ct2/show/NCT01989546
   Google Scholar
• Safety and efficacy study of PRI-724 plus gemcitabine in subjects with advanced or metastatic pancreatic adenocarcinoma. Available from: https://clinicaltrials.gov/ct2/show/NCT01764477
   Google Scholar
• Regorafenib plus gemcitabine in metastatic pancreatic cancer. Available from: https://clinicaltrials.gov/ct2/show/NCT02383433
   Google Scholar
• A Phase 2, multicenter study of FOLFIRINOX followed by ipilimumab with allogenic GM-CSF transfected pancreatic tumor vaccine in the treatment of metastatic pancreatic cancer. Available from: https://clinicaltrials.gov/ct2/show/NCT01896869
   Google Scholar
• Immunotherapy using tumor infiltrating lymphocytes for patients with metastatic cancer. Available from: https://clinicaltrials.gov/ct2/show/NCT01174121
   Google Scholar
• Phase II/pilot study of 2nd generation anti-CEA designer T cells in adenocarcinomas. Available from: https://clinicaltrials.gov/ct2/show/NCT01723306
   Google Scholar
• Investigator’s initiated Phase II study for pancreatic cancer patients. Available from: https://clinicaltrials.gov/ct2/show/NCT01659502
   Google Scholar
• Phase II trial evaluating OS with therasphere® + 2nd-line FOLFOX in pancreatic liver mets. Available from: https://clinicaltrials.gov/ct2/show/NCT01581307
   Google Scholar
• QYHJ Granules versus xeloda in metastatic pancreatic cancer. Available from: https://clinicaltrials.gov/ct2/show/NCT01796782
   Google Scholar
• Open-label Phase 2 efficacy trial of cancer macrobeads in patients with treatment-resistant pancreatic or colorectal cancer. Available from: https://clinicaltrials.gov/ct2/show/NCT01053013
   Google Scholar
• Efficacy and safety of L-asparaginase encapsulated in RBC combined with gemcitabine or FOLFOX in 2nd line for progressive metastatic pancreatic carcinoma. Available from: https://clinicaltrials.gov/ct2/show/NCT02195180
   Google Scholar
• Active symptom control alone or with mFOLFOX chemotherapy for locally advanced/metastatic biliary tract cancers (ABC06). Available from: https://clinicaltrials.gov/ct2/show/NCT01926236
   Google Scholar
• XELOX in advanced biliary tract carcinoma after failure of gemcitabine-based chemotherapy. Available from: https://clinicaltrials.gov/ct2/show/NCT02350686
   Google Scholar
• CAP7.1 for the treatment of advanced stage, therapy refractory lung and biliary tract tumors (CAP7-1). Available from: https://clinicaltrials.gov/ct2/show/NCT02094560
   Google Scholar
• A Phase IIa study of the MEK inhibitor trametinib monotherapy in the treatment of biliary tract cancers. Available from: https://clinicaltrials.gov/ct2/show/NCT01943864
   Google Scholar
• Phase II study of refametinib, a MEK inhibitor, as second-line treatment in advanced biliary tract adenocarcinoma. Available from: https://clinicaltrials.gov/ct2/show/NCT02346032
   Google Scholar
• Phase II study of SPI-1620 in combination with docetaxel as a second-line to treat biliary cancer. Available from: https://clinicaltrials.gov/ct2/show/NCT01773785
   Google Scholar