506
Views
8
CrossRef citations to date
0
Altmetric
Review

Systemic therapy for advanced pancreatic cancer: individualising cytotoxic therapy

, MBBCh BAO MA PhD IMRCS MRCPI (Specialist Registrar in Medical Oncology) & , MBBCh BAO BMedSc MSc MD MRCPI (Consultant in Medical Oncology)

Bibliography

  • UK Cancer Research statistics on pancreatic cancer. 2014. Available from: http://www.cancerresearchuk.org/cancer-info/cancerstats/types/pancreas/
  • SEER data for pancreatic cancer incidence 2004-2010. 2014. Available from: http://seer.cancer.gov/statfacts/html/pancreas.html
  • UK Cancer Research statistics on pancreatic cancer. 2014. Available from: http://www.cancerresearchuk.org/cancer-info/cancerstats/keyfacts/pancreatic-cancer/
  • Smith FP, Hoth DF, Levin B, et al. 5-fluorouracil, Adriamycin and mitomycin-C (FAM) chemotherapy for advanced adenocarcinoma of the pancreas. Cancer 1980;46(9):2014-18
  • Bukowski RM, Abderhalden RT, Hewlett JS, et al. Phase II trial of streptozocin, mitomycin C and 5-fluorouracil in adenocarcinoma of the pancreas. Cancer Clin Trials 1980;3(4):321-4
  • Wiggans RG, Woolley PV, Macdonald JS, et al. PS/Phase II trial of streptozocin, mitomycin-C and 5-fluorouracil (SMF) in the treatment of advanced pancreatic cancer. Cancer 1979;41(2):387-91
  • Stephens RL, Hoogstraten B, Haas C, Clark G. Pancreatic cancer treated with carmustine, fluorouracil and spironolactone: a randomized study. Arch Intern Med 1978;138(1):115-17
  • Porta C, Nastasi G, Spaghi A, Moroni M. Doxorubicin/methotrexate/fluorouracil in advanced pancreatic cancer. Lancet 1990;336(8728):1454-5
  • Mallinson CN, Rake MO, Cocking JB, et al. Chemotherapy in pancreatic cancer: results of a controlled, prospective, randomized, multicenter trial. Br Med J 1980;281(6255):1589-91
  • Horton J, Gelber RD, Engstrom P, et al. Trials of single agent and combination chemotherapy for advanced cancer of the pancreas. Cancer Treat Rep 1981;65(1-2):65-8
  • Rothenberg ML, Moore MJ, Cripps MC, et al. A phase II trial of gemcitabine in patients with 5-FU-refractory pancreas cancer. Ann Oncol 1996;7(4):347-53
  • Burris HAIII, 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(6):2403-13
  • Heinemann V. Gemcitabine in the treatment of advanced pancreatic cancer: a comparative analysis of randomized trials. Semin Oncol 2002;29:9-16
  • Berlin JD, Catalano P, Thomas J, et al. Phase III study of gemcitabine in combination with fluorouracil versus gemcitabine alone in patients with advanced pancreatic carcinoma. Eastern Cooperative Oncology Group E2297. J Clin Oncol 2002;20:3270-5
  • Di Costanzo F, Carlini P, Doni L, et al. Gemcitabine with or without continuous infusion (5-FU) in advanced pancreatic cancer: a randomized phase II trial of the Italian oncology group for clinical research (GOIRC). Br J Cancer 2005;93(2):185-9
  • Reiss H, Helm A, Niedergethmann M, et al. A randomized prospective multicenter phase III trial of gemcitabine, 5-fluorouracil (5-FU), folinic acid vs. gemcitabine alone in patients with advanced pancreatic cancer. J Clin Oncol 2005;23(165):abstract 4009
  • 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 2003;14(1):97-104
  • 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 2007;25:2212-17
  • Bernhard J, Dietrich D, Scheithauer W, et al. Clinical benefit and quality of life in patients with advanced pancreatic cancer receiving gemcitabine plus capecitabine versus gemcitabine alone: a randomized multicenter phase III clinical trial–SAKK 44/00-CECOG/PAN.1.3.001. J Clin Oncol 2008;26(22):3695-701
  • Di Constanzo F, Carlini P, Doni L, et al. Gemcitabine with or without continuous infusional 5-FU in advanced pancreatic cancer: a randomized phase II trial of the Italian Oncology Group for Clinical Research (GOIRC). Br J Cancer 2005;93(2):185-9
  • 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 2009;27(33):5513-18
  • Poplin E, Levy DE, Berlin J, et al. Phase III trial of gemcitabine (30-minute infusion) versus gemcitabine (fixed-dose rate-infusion [FDR]) versus gemcitabine+oxaliplatin (GEMOX) in patients with advanced pancreatic cancer (E6201). J Clin Oncol 2006;24(185):abstract LBA4004
  • 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 2005;23:3509-16
  • Colucci G, Labianca R, di Costanzo F, et al. Randomized phase III trial of gemcitabine plus cisplatin compared with single-agent gemcitabine as first-line treatment of patients with advanced pancreatic cancer: the GIP-1 study. J Clin Oncol 2010;28(10):1645-51
  • Heinemann C, 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 2006;24(24):3946-52
  • Viret F, Ychou M, Lepille D, et al. Gemcitabine in combination with cisplatin (GP) versus gemcitabine alone (G) in the treatment of locally advanced or metastatic pancreatic cancer. Final results of a multicenter randomized phase II study. J Clin Oncol 2004;22(145):abstract 4118
  • 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 Gruppo Oncologica dell’Italia Meridionale. Cancer 2002;94:902-10
  • Heinemann V, Quietzsch D, Gieseler F, et al. Randomized phase III trial of gemcitabine plus cisplatin compared with cisplatin alone in advanced pancreatic cancer. J Clin Oncol 2006;24:3946-52
  • 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 2005;16(10):1639-45
  • Stathopoulos GP, Syrigos K, Aravantinos G, et al. Fountzilas. 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 Cancer 2006;95(5):587-92
  • 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 tumour response rate. J Clin Oncol 2004;22:3776-83
  • O’Reilly EM, Abou-Alfa GK, Letourneau R, et al. A randomized phase III trial of DX-8951f (exactecan mesylate; DX) and gemcitabine (GEM) vs. gemcitabine alone in advanced pancreatic cancer (APC). J Clin Oncol 2004;22(145):abstract 4006
  • Heinemann V, Boeck S, Hinke A, et al. Meta-analysis of randomized trials: evaluation of benefit from gemcitabine-based combination chemotherapy applied in advanced pancreatic cancer. BMC Cancer 2008;8:82
  • Fjallskog MLH, Lejonklou MH, Oberg KE, et al. Expression of molecular targets for tyrosine kinase receptor antagonists in malignant endocrine pancreatic tumours. Clin Cancer Res 2003;9:1469-73
  • Tobita K, Kijilma H, Dowasaki S, et al. Epidermal growth factor receptor expression in human pancreatic cancer. Significance for liver metastasis. Int J Mol Med 2003;11:305-9
  • Xiong HQ. Molecular targeting therapy for pancreatic cancer. Cancer Chemother Pharmacol 2004;54(Suppl 1):S69-77
  • Ueda S, Ogata S, Tsude H, et al. The correlation between cytoplasmic overexpression of epidermal growth factor receptor and tumour aggressiveness: poor prognosis in patients with pancreatic ductal adenocarcinoma. Pancreas 2004;29:E1-8
  • 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 2000;60:2926-35
  • Ng SSW, 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 2002;1:777-83
  • 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 2004;22:1430-8
  • Bramhall SR, Schulz J, Neumanaitis J, et al. A double blind placebo controlled randomized study comparing gemcitabine and marimastat with gemcitabine and placebo as first line therapy in patients with advanced pancreatic cancer. Br J Cancer 2002;87:161-7
  • 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 Cancer Clinical Trials Group. J Clin Oncol 2007;25(15):1960-6
  • De Cunha Santos G, Dhani N, Tu D, et al. Molecular predictors of outcome in a phase 3 study of gemcitabine and erlotinib therapy in patients with advanced pancreatic cancer: National Cancer Institute of Cancer Clinical Trials Group Study PA.3. Cancer 2010;116(24):5599-607
  • Van Cutsem E, Li CP, Nowara E, et al. Dose escalation to rash for erlotinib plus gemcitabine for metastatic pancreatic cancer: the phase II RACHEL study. Br J Cancer 2014;111(11):2067-75
  • Kindler HL, Friberg G, Singh DA, et al. Phase II trial of bevacizumab plus gemcitabine in patients with advanced pancreatic cancer. J Clin Oncol 2005;23(31):8033-40
  • Kindler HL, Niedzwiecki D, Hollis D, et al. Gemcitabine plus bevacizumab compared with gemcitabine plus placebo in patients with advanced pancreatic cancer: phase III trial of the Cancer and Leukaemia Group B (CALGB 80303). J Clin Oncol 2010;28(22):3617-22
  • Kindler HL, Ioka T, Richel DJ, et al. Axitinib plus gemcitabine versus placebo plus gemcitabine in patients with advanced pancreatic adenocarcinoma: a double blind randomized phase 3 study. Lancet Oncol 2011;12(3):256-62
  • Kindler HL, Wroblewski K, Wallace JA, et al. Gemcitabine plus sorafenib in patients with advanced pancreatic cancer: a phase II trial of the University of Chicago Phase II Consortium. Invest New Drugs 2012;30(1):382-6
  • Merchan JR, Ferrell A, Macintyre J, et al. Phase II study of gemcitabine, oxaliplatin and cetuximab in advanced pancreatic cancer. Am J Clin Oncol 2012;35(5):446-50
  • Kullmann F, Hollerbach S, Dollinger MM, et al. Cetuximab plus gemcitabine/oxaliplatin (GEMOXCET) in first line metastatic pancreatic cancer: a multicentre phase II study. Br J Cancer 2009;100(7):1032-6
  • Kindler HL, Richards DA, Garbo LE, et al. A randomized, placebo-controlled phase 2 study of ganitumab (AMG 479) or conatumumab (AMG 655) in combination with gemcitabine in patients with metastatic pancreatic cancer. Ann Oncol 2012;23(11):2834-42
  • Javle MM, 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
  • Conroy T, Desseigne F, Ychou M, et al. for the Groupe Tumeurs Digestives of Unicancer and the PRODIGE intergroup. FOLFIRINOX versus Gemcitabine for metastatic pancreatic cancer. N Engl J Med 2011;364(19):1817-25
  • Frese KK, Neesse A, Cook N, et al. Nab-paclitaxel potentiates gemcitabine activity by reducing cytidine deaminase levels in a mouse model of pancreatic cancer. Cancer Discov 2012;2:260-9
  • Von Hoff DD, Ramanathan RK, Borad MJ, et al. Gemcitabine plus nab-paclitaxel is an active regimen in patients with advanced pancreatic cancer: a phase I/II trial. J Clin Oncol 2011;29:4548-54
  • Von Hoff DD, Ervin TJ, Arena FP, et al. Randomized phase III study of weekly nab-paclitaxel plus gemcitabine versus gemcitabine alone in patients with metastatic adenocarcinoma of the pancreas (MPACT). J Clin Oncol 2013;31(4):LBA148
  • Von Hoff DD, Ervin T, Arena FP, et al. Increased survival in pancreatic cancer with nab-paclitaxel plus gemcitabine. N Engl J Med 2013;369(18):1691-703
  • Miyamoto DT, Mamon HJ, Ryan DP, et al. Outcomes and tolerability of chemoradiation therapy for pancreatic cancer patients aged 75 years or older. Int J Radiat Oncol Biol Phys 2010;77(4):1171-7
  • Vickers MM, Powell ED, Asmis TR, et al. Comorbidity, age and overall survival in patients with advanced pancreatic cancer – results from NCIC CTG PA.2: a phase III trial of gemcitabine plus erlotinib or placebo. Eur J Cancer 2012;48:10-1434-42
  • Tas F, Sen F, Keskin S, et al. Prognostic factors in metastatic pancreatic cancer: older patients are associated with reduced overall survival. Mol Clin Oncol 2013;1(4):788-92
  • Stormiolo AM, Enas NH, Brown CA, et al. An investigational new drug treatment program for patients with gemcitabine: results for over 3000 patients with pancreatic cancer. Cancer 1999;85:1261-8
  • Marechal R, Demois A, Gay F, et al. Prognostic factors and prognostic index for chemonaive and gemcitabine-refractory patients with advanced pancreatic cancer. Oncology 2007;73(1-2):41-51
  • Ueda A, Hosokawa A, Ogawa K, et al. Treatment outcome of advanced pancreatic cancer patients who are ineligible for a clinical trial. Oncol Targets Ther 2013;6:491-6
  • Boeck S, Hinke A, Wilkowski R, Heinemann V. Importance of performance status for treatment outcome in advanced pancreatic cancer. World J Gastroenterol 2007;13(2):224-7
  • Gunturu KS, Yao X, Cong X, et al. FOLFIRINOX for locally advanced and metastatic pancreatic cancer: single institution retrospective review of efficacy and toxicity. Med Oncol 2013;30(1):361
  • Mahaseth H, Brutcher E, Kauh J, et al. Modified FOLFIRINOX regimen with improved safety and maintained efficacy in pancreatic adenocarcinoma. Pancreas 2013;42(8):1311-15
  • Miksad RA, Schnipper L, Goldstein M. Does a statistically significant survival benefit of erlotinib plus gemcitabine for advanced pancreatic cancer translate into clinical significance and value? J Clin Oncol 2007;25(28):4506-7
  • Tam VC, Ko YJ, Mittmann N, et al. Cost-effectiveness of systemic therapies for metastatic pancreatic cancer. Curr Oncol 2013;20(2):e90-e106
  • Sinn M, Sinn BV, Striefler JK, et al. SPARC expression in resected pancreatic cancer patients treated with gemcitabine: results from the CONKO-001 study. Ann Oncol 2014;25(5):1025-32
  • Nixon AB, Pang H, Starr MD, et al. Prognostic and predictive blood-based biomarkers in patients with advanced pancreatic cancer: results from CALGB80303 (Alliance). Clin Cancer Res 2013;19:6957-66
  • Greenhalf W, Ghaneh P, Neoptolemos JP, et al. European Study Group for Pancreatic Cancer. Pancreatic cancer hENT1 expression and survival from gemcitabine in patients from the ESPAC-3 trial. J Natl Cancer Inst 2014;106:1-djt347
  • Herman JM, Fan KY, Wild AT, et al. Correlation of Smad4 status with outcomes in patients receiving erlotinib combined with adjuvant chemoradiation and chemotherapy after resection for pancreatic adenocarcinoma. Int J Radiat Oncol Biol Phys 2013;87(3):458-9

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.