Evolution of systemic therapy for advanced pancreatic cancer

References

• Jemal A, Siegel R, Ward E et al. Cancer statistics, 2008. CA Cancer J. Clin.58, 71–96 (2008).
   PubMed Web of Science ®Google Scholar
• Glimelius B, Hoffman K, Sjoden PO et al. Chemotherapy improves survival and quality of life in advanced pancreatic and biliary cancer. Ann. Oncol.7, 593–600 (1996).
   PubMed Web of Science ®Google Scholar
• Moore MJ, Goldstein D, Hamm J et al. 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.25, 1960–1966 (2007).
   PubMed Web of Science ®Google Scholar
• Oettle H, Post S, Neuhaus P et al. Adjuvant chemotherapy with gemcitabine vs observation in patients undergoing curative-intent resection of pancreatic cancer: a randomized controlled trial. JAMA297, 267–277 (2007).
   PubMed Web of Science ®Google Scholar
• Neoptolemos JP, Buchler M, Stocken DD et al. ESPAC-3(v2): a multicenter, international, open-label, randomized, controlled Phase III trial of adjuvant 5-fluorouracil/folinic acid (5-FU/FA) versus gemcitabine (GEM) in patients with resected pancreatic ductal adenocarcinoma. J. Clin. Oncol.18S, (2009) (Abstract 4505).
   Google Scholar
• Neoptolemos JP, Stocken DD, Tudur Smith C et al. Adjuvant 5-fluorouracil and folinic acid vs observation for pancreatic cancer: composite data from the ESPAC-1 and -3(v1) trials. Br. J. Cancer100, 246–250 (2009).
   PubMed Web of Science ®Google Scholar
• Klinkenbijl JH, Jeekel J, Sahmoud T et al. Adjuvant radiotherapy and 5-fluorouracil after curative resection of cancer of the pancreas and periampullary region: Phase III trial of the EORTC gastrointestinal tract cancer cooperative group. Ann. Surg.230, 776–82 (1999).
   PubMed Web of Science ®Google Scholar
• Neoptolemos JP, Dunn JA, Stocken DD et al. Adjuvant chemoradiotherapy and chemotherapy in resectable pancreatic cancer: a randomised controlled trial. Lancet358, 1576–1585 (2001).
   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.350, 1200–1210 (2004).
   PubMed Web of Science ®Google Scholar
• Yip D, Karapetis C, Strickland A et al. Chemotherapy and radiotherapy for inoperable advanced pancreatic cancer. Cochrane Database Syst. Rev.3, CD002093 (2006).
   Google Scholar
• Sultana A, Tudur Smith C, Cunningham D et al. Systematic review, including meta-analyses, on the management of locally advanced pancreatic cancer using radiation/combined modality therapy. Br. J. Cancer96, 1183–1190 (2007).
   PubMed Web of Science ®Google Scholar
• Marten A, Schmidt J, Ose J et al. A randomized multicentre Phase II trial comparing adjuvant therapy in patients with interferon α-2b and 5-FU alone or in combination with either external radiation treatment and cisplatin (CapRI) or radiation alone regarding event-free survival – CapRI-2. BMC Cancer9, 160 (2009).
   PubMed Web of Science ®Google Scholar
• Keating JJ, Johnson PJ, Cochrane AM et al. A prospective randomised controlled trial of tamoxifen and cyproterone acetate in pancreatic carcinoma. Br. J. Cancer60, 789–792 (1989).
   PubMedGoogle Scholar
• Taylor OM, Benson EA, McMahon MJ. Clinical trial of tamoxifen in patients with irresectable pancreatic adenocarcinoma. The Yorkshire gastrointestinal tumour group. Br. J. Surg.80, 384–386 (1993).
   PubMed Web of Science ®Google Scholar
• Negi SS, Agarwal A, Chaudhary A. Flutamide in unresectable pancreatic adenocarcinoma: a randomized, double-blind, placebo-controlled trial. Invest. New Drugs24, 189–194 (2006).
   PubMedGoogle Scholar
• Sultana A, Smith CT, Cunningham D et al. Meta-analyses of chemotherapy for locally advanced and metastatic pancreatic cancer. J. Clin. Oncol.25, 2607–2615 (2007).
   PubMed Web of Science ®Google Scholar
• Palmer KR, Kerr M, Knowles G et al. Chemotherapy prolongs survival in inoperable pancreatic carcinoma. Br. J. Surg.81, 882–885 (1994).
   PubMed Web of Science ®Google Scholar
• Mallinson CN, Rake MO, Cocking JB et al. Chemotherapy in pancreatic cancer: results of a controlled, prospective, randomised, multicentre trial. BMJ281, 1589–1591 (1980).
   PubMed Web of Science ®Google Scholar
• Crown J, Casper ES, Botet J et al. Lack of efficacy of high-dose leucovorin and fluorouracil in patients with advanced pancreatic adenocarcinoma. J. Clin. Oncol.9, 1682–1686 (1991).
   PubMed Web of Science ®Google Scholar
• Burris HA 3rd, 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.15, 2403–2413 (1997).
   PubMed Web of Science ®Google Scholar
• Hochster HS. Newer approaches to gemcitabine-based therapy of pancreatic cancer: fixed-dose-rate infusion and novel agents. Int. J. Radiat. Oncol. Biol. Phys.56, 24–30 (2003).
   PubMedGoogle Scholar
• Touroutoglou N, Gravel D, Raber MN et al. Clinical results of a pharmacodynamically-based strategy for higher dosing of gemcitabine in patients with solid tumors. Ann. Oncol.9, 1003–1008 (1998).
   PubMed Web of Science ®Google Scholar
• Tempero M, Plunkett W, Ruiz Van Haperen V et al. Randomized Phase II comparison of dose-intense gemcitabine: thirty-minute infusion and fixed dose rate infusion in patients with pancreatic adenocarcinoma. J. Clin. Oncol.21, 3402–3408 (2003).
   PubMed Web of Science ®Google Scholar
• Poplin E, Feng Y, Berlin J et al. Phase III, randomized study of gemcitabine and oxaliplatin versus gemcitabine (fixed-dose rate infusion) compared with gemcitabine (30-minute infusion) in patients with pancreatic carcinoma E6201: a trial of the Eastern Cooperative Oncology Group. J. Clin. Oncol.27, 3778–3785 (2009).
   PubMed Web of Science ®Google Scholar
• Brodowicz T, Wolfram RM, Kostler WJ et al. Phase II study of gemcitabine in combination with cisplatin in patients with locally advanced and/or metastatic pancreatic cancer. Anticancer Drugs11, 623–628 (2000).
   PubMed Web of Science ®Google Scholar
• Heinemann V, Wilke H, Mergenthaler HG et al. Gemcitabine and cisplatin in the treatment of advanced or metastatic pancreatic cancer. Ann. Oncol.11, 1399–1403 (2000).
   PubMed Web of Science ®Google Scholar
• Philip PA, Zalupski MM, Vaitkevicius VK et al. Phase II study of gemcitabine and cisplatin in the treatment of patients with advanced pancreatic carcinoma. Cancer92, 569–577 (2001).
   PubMed Web of Science ®Google Scholar
• Cascinu S, Labianca R, Catalano V et al. Weekly gemcitabine and cisplatin chemotherapy: a well-tolerated but ineffective chemotherapeutic regimen in advanced pancreatic cancer patients. A report from the Italian group for the study of digestive tract cancer (GISCAD). Ann. Oncol.14, 205–208 (2003).
   PubMedGoogle Scholar
• Heinemann V, Quietzsch D, Gieseler F et al. Randomized Phase III trial of gemcitabine plus cisplatin compared with gemcitabine alone in advanced pancreatic cancer. J. Clin. Oncol.24, 3946–3952 (2006).
   PubMed Web of Science ®Google Scholar
• Colucci G, Giuliani F, Gebbia V et al. Gemcitabine alone or with cisplatin for the treatment of patients with locally advanced and/or metastatic pancreatic carcinoma: a prospective, randomized Phase III study of the Gruppo Oncologia dell’Italia Meridionale. Cancer94, 902–910 (2002).
   PubMed Web of Science ®Google Scholar
• Colucci G, Labianca R, Costanza V et al. A randomized trial of gemcitabine versus gemcitabine plus cisplatin in chemotherapy-naive advanced pancreatic adenocarcinoma: the GIP-1 (Gruppo Italiano Pancreas- GOIM/GISCAD/GOIRC) study. J. Clin. Oncol.27 (2009) (Abstract 4504).
   Google Scholar
• Alberts SR, Townley PM, Goldberg RM et al. Gemcitabine and oxaliplatin for metastatic pancreatic adenocarcinoma: a North Central Cancer Treatment Group Phase II study. Ann. Oncol.14, 580–585 (2003).
   PubMed Web of Science ®Google Scholar
• Louvet C, Andre T, Lledo G et al. Gemcitabine combined with oxaliplatin in advanced pancreatic adenocarcinoma: final results of a GERCOR multicenter Phase II study. J. Clin. Oncol.20, 1512–1518 (2002).
   PubMed Web of Science ®Google Scholar
• Louvet C, Labianca R, Hammel P et al. Gemcitabine in combination with oxaliplatin compared with gemcitabine alone in locally advanced or metastatic pancreatic cancer: results of a GERCOR and GISCAD Phase III trial. J. Clin. Oncol.23, 3509–3516 (2005).
   PubMed Web of Science ®Google Scholar
• Heinemann V, Labianca R, Hinke A et al. Increased survival using platinum analog combined with gemcitabine as compared to single-agent gemcitabine in advanced pancreatic cancer: pooled analysis of two randomized trials, the GERCOR/GISCAD intergroup study and a German multicenter study. Ann. Oncol.18, 1652–1659 (2007).
   PubMed Web of Science ®Google Scholar
• Poplin E, Levy D, Berlin J et al. Phase III trial of gemitabine (30-minute infusion) versus gemcitabine (fixed-dose-rate infusion [FDR]) versus gemcitabine + oxaliplatin (GEMOX) in patients with advanced pancreatic cancer (E6201). J. Clin. Oncol.25 (2006) (Abstract LBA4004).
   Google Scholar
• Hess V, Salzberg M, Borner M et al. Combining capecitabine and gemcitabine in patients with advanced pancreatic carcinoma: a Phase I/II trial. J. Clin. Oncol.21, 66–68 (2003).
   PubMed Web of Science ®Google Scholar
• Scheithauer W, Schull B, Ulrich-Pur H et al. Biweekly high-dose gemcitabine alone or in combination with capecitabine in patients with metastatic pancreatic adenocarcinoma: a randomized Phase II trial. Ann. Oncol.14, 97–104 (2003).
   PubMed Web of Science ®Google Scholar
• Cunningham D, Chau I, Stocken D et al. Phase III randomised comparison of gemicitabine (GEM) with gemcitabine plus capecitabine (GEM-CAP) in patients with advanced pancreatic cancer. Eur. J. Cancer3(Suppl.), 12 (2005).
   Google Scholar
• Herrmann R, Bodoky G, Ruhstaller T et al. Gemcitabine plus capecitabine compared with gemcitabine alone in advanced pancreatic cancer: a randomized, multicenter, Phase III trial of the Swiss group for Clinical Cancer Research and the Central European Cooperative Oncology Group. J. Clin. Oncol.25, 2212–2217 (2007).
   PubMed Web of Science ®Google Scholar
• Cunningham D, Chau I, Stocken DD et al. Phase III randomized comparison of gemcitabine versus gemcitabine plus capecitabine in patients with advanced pancreatic cancer. J. Clin. Oncol.27, 5513–5518 (2009).
   PubMed Web of Science ®Google Scholar
• Rocha Lima CM, Green MR, Rotche R et al. Irinotecan plus gemcitabine results in no survival advantage compared with gemcitabine monotherapy in patients with locally advanced or metastatic pancreatic cancer despite increased tumor response rate. J. Clin. Oncol.22, 3776–3783 (2004).
   PubMed Web of Science ®Google Scholar
• Oettle H, Richards D, Ramanathan RK et al. A Phase III trial of pemetrexed plus gemcitabine versus gemcitabine in patients with unresectable or metastatic pancreatic cancer. Ann. Oncol.16, 1639–1645 (2005).
   PubMed Web of Science ®Google Scholar
• O’Reilly R, Abou-Alfa G, Letourneau R et al. A randomized Phase III trial of DX-8951f (exatecan mesylate; DX) and gemicitabine (GEM) vs. gemcitabine alone in advanced pancreatic cancer (APC). J. Clin. Oncol.23, (2004) (Abstract LBA4006).
   Google Scholar
• Shepard RC, Levy DE, Berlin JD et al. Phase II study of gemcitabine in combination with docetaxel in patients with advanced pancreatic carcinoma (E1298). A trial of the Eastern Cooperative Oncology Group. Oncology66, 303–309 (2004).
   PubMedGoogle Scholar
• Stathopoulos GP, Syrigos K, Aravantinos G et al. A multicenter Phase III trial comparing irinotecan–gemcitabine (IG) with gemcitabine (G) monotherapy as first-line treatment in patients with locally advanced or metastatic pancreatic cancer. Br. J. Cancer95, 587–592 (2006).
   PubMed Web of Science ®Google Scholar
• Pelzer U, Kubica K, Stieler J et al. A randomized trial in patients with gemcitabine refractory pancreatic cancer. final results of the CONKO 003 study. J. Clin. Oncol.26 (2008) (Abstract 4508).
   Google Scholar
• Yoo C, Hwang JY, Kim JE et al. A randomised Phase II study of modified FOLFIRI.3 vs modified FOLFOX as second-line therapy in patients with gemcitabine-refractory advanced pancreatic cancer. Br. J. Cancer101, 1658–1663 (2009).
   PubMed Web of Science ®Google Scholar
• Xiong HQ. Molecular targeting therapy for pancreatic cancer. Cancer Chemother. Pharmacol.54(Suppl. 1), S69–S77 (2004).
   PubMed Web of Science ®Google Scholar
• Fjallskog ML, Lejonklou MH, Oberg KE et al. Expression of molecular targets for tyrosine kinase receptor antagonists in malignant endocrine pancreatic tumors. Clin. Cancer Res.9, 1469–1473 (2003).
   PubMed Web of Science ®Google Scholar
• Tobita K, Kijima H, Dowaki S et al. Epidermal growth factor receptor expression in human pancreatic cancer: significance for liver metastasis. Int. J. Mol. Med.11, 305–309 (2003).
   PubMed Web of Science ®Google Scholar
• Ueda S, Ogata S, Tsuda H et al. The correlation between cytoplasmic overexpression of epidermal growth factor receptor and tumor aggressiveness: poor prognosis in patients with pancreatic ductal adenocarcinoma. Pancreas29, e1–e8 (2004).
   PubMedGoogle Scholar
• Ng SS, Tsao MS, Nicklee T et al. Effects of the epidermal growth factor receptor inhibitor OSI-774, tarceva, on downstream signaling pathways and apoptosis in human pancreatic adenocarcinoma. Mol. Cancer Ther.1, 777–783 (2002).
   PubMed Web of Science ®Google Scholar
• Bruns CJ, Solorzano CC, Harbison MT et al. Blockade of the epidermal growth factor receptor signaling by a novel tyrosine kinase inhibitor leads to apoptosis of endothelial cells and therapy of human pancreatic carcinoma. Cancer Res.60, 2926–2935 (2000).
   PubMed Web of Science ®Google Scholar
• Almoguera C, Shibata D, Forrester K et al. Most human carcinomas of the exocrine pancreas contain mutant c-K-ras genes. Cell53, 549–554 (1988).
   PubMed Web of Science ®Google Scholar
• Bruns CJ, Harbison MT, Davis DW et al. Epidermal growth factor receptor blockade with C225 plus gemcitabine results in regression of human pancreatic carcinoma growing orthotopically in nude mice by antiangiogenic mechanisms. Clin. Cancer Res.6, 1936–1948 (2000).
   PubMed Web of Science ®Google Scholar
• Furukawa T. Molecular pathology of pancreatic cancer: implications for molecular targeting therapy. Clin. Gastroenterol. Hepatol.7, S35–S39 (2009).
   Google Scholar
• Hezel AF, Kimmelman AC, Stanger BZ et al. Genetics and biology of pancreatic ductal adenocarcinoma. Genes Dev.20, 1218–1249 (2006).
   PubMed Web of Science ®Google Scholar
• Cohen SJ, Ho L, Ranganathan S et al. Phase II and pharmacodynamic study of the farnesyltransferase inhibitor R115777 as initial therapy in patients with metastatic pancreatic adenocarcinoma. J. Clin. Oncol.21, 1301–1306 (2003).
   PubMed Web of Science ®Google Scholar
• Van Cutsem E, van de Velde H, Karasek P et al. Phase III trial of gemcitabine plus tipifarnib compared with gemcitabine plus placebo in advanced pancreatic cancer. J. Clin. Oncol.22, 1430–1438 (2004).
   PubMed Web of Science ®Google Scholar
• Wilhelm SM, Carter C, Tang L et al. BAY 43-9006 exhibits broad spectrum oral antitumor activity and targets the RAF/MEK/ERK pathway and receptor tyrosine kinases involved in tumor progression and angiogenesis. Cancer Res.64, 7099–7109 (2004).
   PubMed Web of Science ®Google Scholar
• Sebolt-Leopold JS, Dudley DT, Herrera R et al. Blockade of the MAP kinase pathway suppresses growth of colon tumors in vivo.Nat. Med.5, 810–816 (1999).
   PubMed Web of Science ®Google Scholar
• Schlieman MG, Fahy BN, Ramsamooj R et al. Incidence, mechanism and prognostic value of activated AKT in pancreas cancer. Br. J. Cancer89, 2110–2115 (2003).
   PubMed Web of Science ®Google Scholar
• Luo J, Manning BD, Cantley LC. Targeting the PI3K–akt pathway in human cancer: rationale and promise. Cancer Cell4, 257–262 (2003).
   PubMed Web of Science ®Google Scholar
• Bondar VM, Sweeney-Gotsch B, Andreeff M et al. Inhibition of the phosphatidylinositol 3´-kinase–AKT pathway induces apoptosis in pancreatic carcinoma cells in vitro and in vivo.Mol. Cancer Ther.1, 989–997 (2002).
   PubMed Web of Science ®Google Scholar
• Bruns CJ, Koehl GE, Guba M et al. Rapamycin-induced endothelial cell death and tumor vessel thrombosis potentiate cytotoxic therapy against pancreatic cancer. Clin. Cancer Res.10, 2109–2119 (2004).
   PubMed Web of Science ®Google Scholar
• Asano T, Yao Y, Zhu J et al. The rapamycin analog CCI-779 is a potent inhibitor of pancreatic cancer cell proliferation. Biochem. Biophys. Res. Commun.331, 295–302 (2005).
   PubMed Web of Science ®Google Scholar
• Ito D, Fujimoto K, Mori T et al.In vivo antitumor effect of the mTOR inhibitor CCI-779 and gemcitabine in xenograft models of human pancreatic cancer. Int. J. Cancer118, 2337–2343 (2006).
   PubMed Web of Science ®Google Scholar
• Asano T, Yao Y, Zhu J et al. The PI 3-kinase/Akt signaling pathway is activated due to aberrant PTEN expression and targets transcription factors NF-κB and c-myc in pancreatic cancer cells. Oncogene23, 8571–8580 (2004).
   PubMed Web of Science ®Google Scholar
• Arlt A, Gehrz A, Muerkoster S et al. Role of NF-κB and Akt/PI3K in the resistance of pancreatic carcinoma cell lines against gemcitabine-induced cell death. Oncogene22, 3243–3251 (2003).
   PubMed Web of Science ®Google Scholar
• Dong QG, Sclabas GM, Fujioka S et al. The function of multiple IκB:NF-κB complexes in the resistance of cancer cells to taxol-induced apoptosis. Oncogene21, 6510–6519 (2002).
   PubMed Web of Science ®Google Scholar
• Li L, Aggarwal BB, Shishodia S et al. Nuclear factor-κB and IκB kinase are constitutively active in human pancreatic cells, and their down-regulation by curcumin (diferuloylmethane) is associated with the suppression of proliferation and the induction of apoptosis. Cancer101, 2351–2362 (2004).
   PubMed Web of Science ®Google Scholar
• Korc M. Pathways for aberrant angiogenesis in pancreatic cancer. Mol. Cancer2, 8 (2003).
   PubMedGoogle Scholar
• Karayiannakis AJ, Bolanaki H, Syrigos KN et al. Serum vascular endothelial growth factor levels in pancreatic cancer patients correlate with advanced and metastatic disease and poor prognosis. Cancer Lett.194, 119–124 (2003).
   PubMed Web of Science ®Google Scholar
• Baker CH, Solorzano CC, Fidler IJ. Blockade of vascular endothelial growth factor receptor and epidermal growth factor receptor signaling for therapy of metastatic human pancreatic cancer. Cancer Res.62, 1996–2003 (2002).
   PubMed Web of Science ®Google Scholar
• Bockhorn M, Tsuzuki Y, Xu L et al. Differential vascular and transcriptional responses to anti-vascular endothelial growth factor antibody in orthotopic human pancreatic cancer xenografts. Clin. Cancer Res.9, 4221–4226 (2003).
   PubMed Web of Science ®Google Scholar
• Solorzano CC, Baker CH, Bruns CJ et al. Inhibition of growth and metastasis of human pancreatic cancer growing in nude mice by PTK 787/ZK222584, an inhibitor of the vascular endothelial growth factor receptor tyrosine kinases. Cancer Biother. Radiopharm.16, 359–370 (2001).
   PubMed Web of Science ®Google Scholar
• Bramhall SR, Schulz J, Nemunaitis J et al. A double-blind placebo-controlled, randomised study comparing gemcitabine and marimastat with gemcitabine and placebo as first line therapy in patients with advanced pancreatic cancer. Br. J. Cancer87, 161–167 (2002).
   PubMed Web of Science ®Google Scholar
• Brown PD, Giavazzi R: Matrix metalloproteinase inhibition: a review of anti-tumour activity. Ann. Oncol.6, 967–974 (1995).
   PubMed Web of Science ®Google Scholar
• Hidalgo M, Maitra A: The hedgehog pathway and pancreatic cancer. N. Engl. J. Med.361, 2094–2096 (2009).
   PubMed Web of Science ®Google Scholar
• Jonker DJ, O’Callaghan CJ, Karapetis CS et al. Cetuximab for the treatment of colorectal cancer. N. Engl. J. Med.357, 2040–2048 (2007).
   PubMed Web of Science ®Google Scholar
• Van Cutsem E, Peeters M, Siena S et al. Open-label Phase III trial of panitumumab plus best supportive care compared with best supportive care alone in patients with chemotherapy-refractory metastatic colorectal cancer. J. Clin. Oncol.25, 1658–1664 (2007).
   PubMed Web of Science ®Google Scholar
• Shepherd FA, Rodrigues Pereira J, Ciuleanu T et al. Erlotinib in previously treated non-small-cell lung cancer. N. Engl. J. Med.353, 123–132 (2005).
   PubMed Web of Science ®Google Scholar
• Moore MJ, da Cunha Santos G, Kamel-Reid S et al. The relationship of K-ras mutations and EGFR gene copy number to outcome in patients treated with erlotinib on National Cancer Institute of Canada Clinical Trials Group trial study PA.3. J. Clin. Oncol.25, (2007) (Abstract 4521).
   Google Scholar
• Kulke MH, Blaszkowsky LS, Ryan DP et al. Capecitabine plus erlotinib in gemcitabine-refractory advanced pancreatic cancer. J. Clin. Oncol.25, 4787–4792 (2007).
   PubMed Web of Science ®Google Scholar
• Tang P, Gill S, Au HJ et al. Phase II trial of erlotinib in advanced pancreatic cancer. J. Clin. Oncol.27 (2009) (Abstract 4609).
   Google Scholar
• Xiong HQ, Rosenberg A, LoBuglio A et al. Cetuximab, a monoclonal antibody targeting the epidermal growth factor receptor, in combination with gemcitabine for advanced pancreatic cancer: a multicenter Phase II trial. J. Clin. Oncol.22, 2610–2616 (2004).
   PubMed Web of Science ®Google Scholar
• Philip P, Benedetti J, Fenoglio-Preiser C et al. Phase III study of gemcitabine [G] plus cetuximab [C] versus gemcitabine in patients [pts] with locally advanced or metastatic pancreatic adenocarcinoma [PC]: SWOG S0205 study. J. Clin. Oncol.25 (2007) (Abstract LBA4509).
   PubMedGoogle Scholar
• Cascinu S, Berardi R, Labianca R et al. Cetuximab plus gemcitabine and cisplatin compared with gemcitabine and cisplatin alone in patients with advanced pancreatic cancer: a randomised, multicentre, Phase II trial. Lancet Oncol.9, 39–44 (2008).
   PubMed Web of Science ®Google Scholar
• Hurwitz H, Fehrenbacher L, Novotny W et al. Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer. N. Engl. J. Med.350, 2335–2342 (2004).
   PubMed Web of Science ®Google Scholar
• Sandler A, Gray R, Perry MC et al. Paclitaxel–carboplatin alone or with bevacizumab for non-small-cell lung cancer. N. Engl. J. Med.355, 2542–2550 (2006).
   PubMed Web of Science ®Google Scholar
• Kindler HL, Friberg G, Singh DA et al. Phase II trial of bevacizumab plus gemcitabine in patients with advanced pancreatic cancer. J. Clin. Oncol.23, 8033–8040 (2005).
   PubMed Web of Science ®Google Scholar
• Kindler H, Niedzwiecki D, Hollis D et al. A double-blind, placebo-controlled, randomized Phase III trial of gemcitabine (G) plus bevacizumab (B) versus gemcitabine plus placebo (P) in patients (pts) with advanced pancreatic cancer (PC): a preliminary analysis of Cancer and Leukemia Group B (CALGB). J. Clin. Oncol.25, (2007) (Abstract 4508).
   Google Scholar
• Spano JP, Chodkiewicz C, Maurel J et al. Efficacy of gemcitabine plus axitinib compared with gemcitabine alone in patients with advanced pancreatic cancer: an open-label randomised Phase II study. Lancet371, 2101–2108 (2008).
   PubMed Web of Science ®Google Scholar
• Kindler HL, Gangadhar T, Karrison T et al. Final analysis of a randomized Phase II study of bevacizumab (B) and gemcitabine (G) plus cetuximab (C) or erlotinib (E) in patients (pts) with advanced pancreatic cancer (PC). J. Clin. Oncol.26, (2008) (Abstract 4502).
   Google Scholar
• Van Cutsem E, Vervenne WL, Bennouna J et al. Phase III trial of bevacizumab in combination with gemcitabine and erlotinib in patients with metastatic pancreatic cancer. J. Clin. Oncol.27, 2231–2237 (2009).
   PubMed Web of Science ®Google Scholar
• Motzer RJ, Escudier S, Oudard S et al. RAD001 vs. placebo in patients with metastatic renal cell carcinoma (RCC) after progression on VEGFr-TKI therapy: results from a randomized, double-blind, multicenter Phase II study. J. Clin. Oncol.26 (2008) (Abstract 5026).
   PubMedGoogle Scholar
• Wolpin BM, Hezel AF, Abrams T et al. Oral mTOR inhibitor everolimus in patients with gemcitabine-refractory metastatic pancreatic cancer. J. Clin. Oncol.27, 193–198 (2009).
   PubMed Web of Science ®Google Scholar
• Dhillon N, Aggarwal BB, Newman RA et al. Phase II trial of curcumin in patients with advanced pancreatic cancer. Clin. Cancer Res.14, 4491–4499 (2008).
   PubMed Web of Science ®Google Scholar
• Moore MJ, Hamm J, Dancey J et al. Comparison of gemcitabine versus the matrix metalloproteinase inhibitor BAY 12-9566 in patients with advanced or metastatic adenocarcinoma of the pancreas: a Phase III trial of the National Cancer Institute of Canada Clinical Trials Group. J. Clin. Oncol.21, 3296–3302 (2003).
   PubMed Web of Science ®Google Scholar
• Black JW. Reflections on some pilot trials of gastrin receptor blockade in pancreatic cancer. Eur. J. Cancer45, 360–364 (2009).
   PubMedGoogle Scholar
• Chau I, Cunningham D, Russell C et al. Gastrazole (JB95008), a novel CCK2/gastrin receptor antagonist, in the treatment of advanced pancreatic cancer: results from two randomised controlled trials. Br. J. Cancer94, 1107–1115 (2006).
   PubMed Web of Science ®Google Scholar
• Philip PA, Mooney M, Jaffe D et al. Consensus report of the National Cancer Institute clinical trials planning meeting on pancreas cancer treatment. J. Clin. Oncol.27(33), 5660–5669 (2009).
   PubMed Web of Science ®Google Scholar
• Chua YJ, Zalcberg JR. Pancreatic cancer – is the wall crumbling. Ann. Oncol.19, 1224–1230 (2008).
   PubMed Web of Science ®Google Scholar
• Jimeno A, Solomon A, Karikari C et al. A prospective validation of a direct tumor xenograft model in pancreatic ductal adenocarcinoma (PDA). J. Clin. Oncol.26, (2008) (Abstract 4500).
   Google Scholar
• Cunningham D, Humblet Y, Siena S et al. Cetuximab monotherapy and cetuximab plus irinotecan in irinotecan-refractory metastatic colorectal cancer. N. Engl. J. Med.351, 337–345 (2004).
   PubMed Web of Science ®Google Scholar
• Van Cutsem E, Humblet Y, Gelderblom H et al. Cetuximab dose-escaltion study in patients with metastatic colorectal cancer with no or slight skin reaction on cetusiman standard dose treatment (EVEREST): Pharmacokinetic and efficacy data of a randomized study. Proceedings of the Gastrointesticanal Cancers Symposium (2007) (Abstract 237).
   Google Scholar
• Hughes AN, O’Brien ME, Petty WJ et al. Overcoming CYP1A1/1A2 mediated induction of metabolism by escalating erlotinib dose in current smokers. J. Clin. Oncol.27, 1220–1226 (2009).
   PubMed Web of Science ®Google Scholar
• Lynch TJ, Bell DW, Sordella R et al. Activating mutations in the epidermal growth factor receptor underlying responsiveness of non-small-cell lung cancer to gefitinib. N. Engl. J. Med.350, 2129–2139 (2004).
   PubMed Web of Science ®Google Scholar
• Mok T, Wu Y, Thongprasert S et al. Phase III, randomised, open-label, first-line study of gefitinib vs carboplatin/paclitaxel in clinically selected patients with advanced non-small-cell lung cancer (IPASS). 33rd ESMO (2008) (Abstract).
   Google Scholar
• Karapetis CS, Khambata-Ford S, Jonker DJ et al.K-ras mutations and benefit from cetuximab in advanced colorectal cancer. N. Engl. J. Med.359, 1757–1765 (2008).
   PubMed Web of Science ®Google Scholar
• Peeters M, Siena S, Van Cutsem E et al. Association of progression-free survival, overall survival, and patient-reported outcomes by skin toxicity and KRAS status in patients receiving panitumumab monotherapy. Cancer115(7), 1544–1554 (2009).
   PubMed Web of Science ®Google Scholar
• Farrell JJ, Elsaleh H, Garcia M et al. Human equilibrative nucleoside transporter 1 levels predict response to gemcitabine in patients with pancreatic cancer. Gastroenterology136, 187–195 (2009).
   PubMed Web of Science ®Google Scholar
• Nakahira S, Nakamori S, Tsujie M et al. Involvement of ribonucleotide reductase M1 subunit overexpression in gemcitabine resistance of human pancreatic cancer. Int. J. Cancer120, 1355–1363 (2007).
   PubMed Web of Science ®Google Scholar
• Bengala C, Guarneri V, Giovannetti E et al. Prolonged fixed dose rate infusion of gemcitabine with autologous haemopoietic support in advanced pancreatic adenocarcinoma. Br. J. Cancer93, 35–40 (2005).
   PubMed Web of Science ®Google Scholar
• Biankin AV, Kench JG, Colvin EK et al. Expression of S100A2 calcium-binding protein predicts response to pancreatectomy for pancreatic cancer. Gastroenterology137, 558–568, 568.e1–11 (2009).
   PubMedGoogle Scholar
• Kamikozuru H, Kuramochi H, Hayashi K et al. ERCC1 codon 118 polymorphism is a useful prognostic marker in patients with pancreatic cancer treated with platinum-based chemotherapy. Int. J. Oncol.32, 1091–1096 (2008).
   PubMed Web of Science ®Google Scholar
• Van Cutsem E, Verslype C, Grusenmeyer PA. Lessons learned in the management of advanced pancreatic cancer. J. Clin. Oncol.25, 1949–1952 (2007).
   PubMedGoogle Scholar
• Tol J, Koopman M, Cats A et al. Chemotherapy, bevacizumab, and cetuximab in metastatic colorectal cancer. N. Engl. J. Med.360, 563–572 (2009).
   PubMed Web of Science ®Google Scholar
• Hecht JR, Mitchell E, Chidiac T et al. A randomized Phase IIIB trial of chemotherapy, bevacizumab, and panitumumab compared with chemotherapy and bevacizumab alone for metastatic colorectal cancer. J. Clin. Oncol.27, 672–680 (2009).
   PubMed Web of Science ®Google Scholar
• Riess H, Pelzer U, Hilbig A et al. Rationale and design of PROSPECT-CONKO 004: a prospective, randomized trial of simultaneous pancreatic cancer treatment with enoxaparin and chemotherapy. BMC Cancer8, 361 (2008).
   PubMedGoogle Scholar