Recent developments in palliative chemotherapy for locally advanced and metastatic pancreas cancer

World Journal of Gastroenterology

Volumn 16, Issue 6, 2010, Pages 673-682

  Bayraktar, Soley ^a   Bayraktar, Ulas Darda ^a   Rocha Lima, Caio Max ^a  

^a UNIVERSITY OF MIAMI   (United States)

Author keywords

Adjuvant therapy; Chemotherapy; Palliative therapy; Pancreas cancer; Radiotherapy

Indexed keywords

AMG 655; ANTINEOPLASTIC AGENT; BEVACIZUMAB; CA 19-9 ANTIGEN; CAPECITABINE; CETUXIMAB; CIPROFLOXACIN; CISPLATIN; CYTOTOXIC AGENT; DOCETAXEL; EPIRUBICIN; ERLOTINIB; EXATECAN; FLUOROURACIL; GEMCITABINE; GRANULOCYTE COLONY STIMULATING FACTOR; IRINOTECAN; MONOCLONAL ANTIBODY; OXALIPLATIN; PACLITAXEL; RUBITECAN; SORAFENIB; UNCLASSIFIED DRUG;

ADVANCED CANCER; BONE MARROW SUPPRESSION; CANCER CELL; CANCER CHEMOTHERAPY; CANCER LOCALIZATION; CANCER PALLIATIVE THERAPY; CANCER SURVIVAL; CELL SURVIVAL; CLINICAL PRACTICE; DIARRHEA; DISEASE FREE SURVIVAL; DRUG EFFICACY; FATIGUE; FLU LIKE SYNDROME; HUMAN; LETHARGY; METASTASIS; MULTIPLE CYCLE TREATMENT; NAUSEA AND VOMITING; NEUTROPENIA; OVERALL SURVIVAL; PANCREAS CANCER; PERIPHERAL EDEMA; PROGRESSION FREE SURVIVAL; QUALITY OF LIFE; REVIEW; SYSTEMIC THERAPY; THROMBOCYTOPENIA; TREATMENT FAILURE; TREATMENT RESPONSE; TUMOR GROWTH; TUMOR VOLUME; VOMITING;

EID: 76849083238     PISSN: 10079327     EISSN: None     Source Type: Journal    
DOI: 10.3748/wjg.v16.i6.673     Document Type: Review

References (71)

1. Jemal A, Siegel R, Ward E, Hao Y, Xu J, Thun MJ. Cancer statistics, 2009. CA Cancer J Clin 2009; 59: 225-249
2. American Cancer Society. Cancer Facts and Figures 2009. Available from: URL: http://www.cancer.org/downloads/2009-500809web.pdf
3. Evans DB, Abbruzzese JL, Rich TA. Cancer of the pancreas. In: De Vita VT Jr, Hellman S, Rosenberg SA, editors. Cancer: Principles and Practice of Oncology. 5th ed. Philadelphia, PA, Lippincott-Raven, 1997: 1054-1087
4. Glimelius B, Hoffman K, Sjödén PO, Jacobsson G, Sellström H, Enander LK, Linné T, Svensson C. Chemotherapy improves survival and quality of life in advanced pancreatic and biliary cancer. Ann Oncol 1996; 7: 593-600
5. Palmer KR, Kerr M, Knowles G, Cull A, Carter DC, Leonard RC. Chemotherapy prolongs survival in inoperable pancreatic carcinoma. Br J Surg 1994; 81: 882-885
6. Mallinson CN, Rake MO, Cocking JB, Fox CA, Cwynarski MT, Diffey BL, Jackson GA, Hanley J, Wass VJ. Chemotherapy in pancreatic cancer: results of a controlled, prospective, randomised, multicentre trial. Br Med J 1980; 281: 1589-1591
7. Burris HA 3rd, Moore MJ, Andersen J, Green MR, Rothenberg ML, Modiano MR, Cripps MC, Portenoy RK, Storniolo AM, Tarassoff P, Nelson R, Dorr FA, Stephens CD, Von Hoff DD. 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: 2403-2413
8. Casper ES, Green MR, Kelsen DP, Heelan RT, Brown TD, Flombaum CD, Trochanowski B, Tarassoff PG. Phase II trial of gemcitabine (2,2'- difluorodeoxycytidine) in patients with adenocarcinoma of the pancreas. Invest New Drugs 1994; 12: 29-34
9. Grunewald R, Abbruzzese JL, Tarassoff P, Plunkett W. Saturation of 2',2'-difluorodeoxycytidine 5'-triphosphate accumulation by mononuclear cells during a phase I trial of gemcitabine. Cancer Chemother Pharmacol 1991; 27: 258-262
10. Tempero M, Plunkett W, Ruiz Van Haperen V, Hainsworth J, Hochster H, Lenzi R, Abbruzzese J. Randomized phase II comparison of dose-intense gemcitabine: thirty-minute infusion and fixed dose rate infusion in patients with pancreatic adenocarcinoma. J Clin Oncol 2003; 21: 3402-3408
11. Poplin E, Feng Y, Berlin J, Rothenberg ML, Hochster H, Mitchell E, Alberts S, O'Dwyer P, Haller D, Catalano P, Cella D, Benson AB 3rd. Phase III, randomized study of gemcitabine and oxaliplatin versus gemcitabine (fixeddose 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 2009; 27: 3778-3785
12. Berlin JD, Catalano P, Thomas JP, Kugler JW, Haller DG, Benson AB 3rd. Phase III study of gemcitabine in combination with fluorouracil versus gemcitabine alone in patients with advanced pancreatic carcinoma: Eastern Cooperative Oncology Group Trial E2297. J Clin Oncol 2002; 20: 3270-3275
13. Riess H, Helm A, Niedergethmann M, Schmidt-Wolf I, Moik M, Hammer C, Zippel K, Weigang-Köhler K, Stauch M, Oettle H. 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: 310s (abstract LBA4009)
14. Hess V, Salzberg M, Borner M, Morant R, Roth AD, Ludwig C, Herrmann R. Combining capecitabine and gemcitabine in patients with advanced pancreatic carcinoma: a phase I/II trial. J Clin Oncol 2003; 21: 66-68
15. Scheithauer W, Schüll B, Ulrich-Pur H, Schmid K, Raderer M, Haider K, Kwasny W, Depisch D, Schneeweiss B, Lang F, Kornek GV. 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: 97-104
16. Herrmann R, Bodoky G, Ruhstaller T, Glimelius B, Saletti P, Bajetta E, Schueller J, Bernhard J, Dietrich D, Scheithauer W. Gemcitabine (G) plus Capecitabine (C) versus alone in locally advanced or metastatic pancreatic cancer. A randomized phase III study of the Swiss Group for Clinical Cancer Research (SAKK) and the Central European Cooperative Oncology Group (CECOG). J Clin Oncol 2005; 23 Suppl 1: 310s (abstract LBA4010)
17. Cunningham D, Chau I, Stocken DD, Valle JW, Smith D, Steward W, Harper PG, Dunn J, Tudur-Smith C, West J, Falk S, Crellin A, Adab F, Thompson J, Leonard P, Ostrowski J, Eatock M, Scheithauer W, Herrmann R, Neoptolemos JP. Phase III randomized comparison of gemcitabine versus gemcitabine plus capecitabine in patients with advanced pancreatic cancer. J Clin Oncol 2009; 27: 5513-5518
18. Bernhard J, Dietrich D, Scheithauer W, Gerber D, Bodoky G, Ruhstaller T, Glimelius B, Bajetta E, Schüller J, Saletti P, Bauer J, Figer A, Pestalozzi BC, Köhne CH, Mingrone W, Stemmer SM, Tàmas K, Kornek GV, Koeberle D, Herrmann R. 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: 3695-3701
19. Heinemann V, Quietzsch D, Gieseler F, Gonnermann M, Schönekäs H, Rost A, Neuhaus H, Haag C, Clemens M, Heinrich B, Vehling-Kaiser U, Fuchs M, Fleckenstein D, Gesierich W, Uthgenannt D, Einsele H, Holstege A, Hinke A, Schalhorn A, Wilkowski R. Randomized phase III trial of gemcitabine plus cisplatin compared with gemcitabine alone in advanced pancreatic cancer. J Clin Oncol 2006; 24: 3946-3952
20. Colucci G, Giuliani F, Gebbia V, Biglietto M, Rabitti P, Uomo G, Cigolari S, Testa A, Maiello E, Lopez M. 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. Cancer 2002; 94: 902-910
21. Faivre S, Raymond E, Woynarowski JM, Cvitkovic E. Supraadditive effect of 2',2'-difluorodeoxycytidine (gemcitabine) in combination with oxaliplatin in human cancer cell lines. Cancer Chemother Pharmacol 1999; 44: 117-123
22. Louvet C, André T, Lledo G, Hammel P, Bleiberg H, Bouleuc C, Gamelin E, Flesch M, Cvitkovic E, de Gramont A. Gemcitabine combined with oxaliplatin in advanced pancreatic adenocarcinoma: final results of a GERCOR multicenter phase II study. J Clin Oncol 2002; 20: 1512-1518
23. Louvet C, Labianca R, Hammel P, Lledo G, Zampino MG, André T, Zaniboni A, Ducreux M, Aitini E, Taïeb J, Faroux R, Lepere C, de Gramont A. 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: 3509-3516
24. Heinemann V, Boeck S, Hinke A, Labianca R, Louvet C. Meta-analysis of randomized trials: evaluation of benefit from gemcitabine-based combination chemotherapy applied in advanced pancreatic cancer. BMC Cancer 2008; 8: 82
25. Wagener DJ, Verdonk HE, Dirix LY, Catimel G, Siegenthaler P, Buitenhuis M, Mathieu-Boué A, Verweij J. Phase II trial of CPT-11 in patients with advanced pancreatic cancer, an EORTC early clinical trials group study. Ann Oncol 1995; 6: 129-132
26. Rocha Lima CM, Savarese D, Bruckner H, Dudek A, Eckardt J, Hainsworth J, Yunus F, Lester E, Miller W, Saville W, Elfring GL, Locker PK, Compton LD, Miller LL, Green MR. Irinotecan plus gemcitabine induces both radiographic and CA 19-9 tumor marker responses in patients with previously untreated advanced pancreatic cancer. J Clin Oncol 2002; 20: 1182-1191
27. Rocha Lima CM, Green MR, Rotche R, Miller WH Jr, Jeffrey GM, Cisar LA, Morganti A, Orlando N, Gruia G, Miller LL. 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 2004; 22: 3776-3783
28. Cheverton P, Friess H, Andras C, Salek T, Geddes C, Bodoky G, Valle J, Humblet Y. Phase III results of exatecan (DX-8951f) versus gemcitabine (Gem) in chemotherapy-naive patients with advanced pancreatic cancer (APC). J Clin Oncol 2004; 23 Suppl 15: abstract LBA4005
29. O'Reilly EM, Lenzi R, Mani S, Schwartz GK, Sharma S, Kelsen DP, Levin A, Danna M, Bridget H, Jager RD. A randomized phase III trial of DX 8951f (exatecan mesylate; DX) and gemcitabine (GEM) vs. gemcitabine alone in advanced pancreatic cancer (APC). J Clin Oncol 2004; 23 Suppl 15: abstract LBA4006
30. Stehlin JS, Giovanella BC, Natelson EA, De Ipolyi PD, Coil D, Davis B, Wolk D, Wallace P, Trojacek A. A study of 9-nitrocamptothecin (RFS-2000) in patients with advanced pancreatic cancer. Int J Oncol 1999; 14: 821-831
31. Konstadoulakis MM, Antonakis PT, Tsibloulis BG, Stathopoulos GP, Manouras AP, Mylonaki DB, Golematis BX. A phase II study of 9-nitrocamptothecin in patients with advanced pancreatic adenocarcinoma. Cancer Chemother Pharmacol 2001; 48: 417-420
32. Cascinu S, Gasparini G, Catalano V, Silva RR, Pancera G, Morabito A, Giordani P, Gattuso D, Catalano G. A phase I-II study of gemcitabine and docetaxel in advanced pancreatic cancer: a report from the Italian Group for the Study of Digestive Tract Cancer (GISCAD). Ann Oncol 1999; 10: 1377-1379
33. Stathopoulos GP, Mavroudis D, Tsavaris N, Kouroussis C, Aravantinos G, Agelaki S, Kakolyris S, Rigatos SK, Karabekios S, Georgoulias V. Treatment of pancreatic cancer with a combination of docetaxel, gemcitabine and granulocyte colony-stimulating factor: a phase II study of the Greek Cooperative Group for Pancreatic Cancer. Ann Oncol 2001; 12: 101-103
34. Ryan DP, Kulke MH, Fuchs CS, Grossbard ML, Grossman SR, Morgan JA, Earle CC, Shivdasani R, Kim H, Mayer RJ, Clark JW. A Phase II study of gemcitabine and docetaxel in patients with metastatic pancreatic carcinoma. Cancer 2002; 94: 97-103
35. Shepard RC, Levy DE, Berlin JD, Stuart K, Harris JE, Aviles V, Thomas JP, Benson AB 3rd. Phase II study of gemcitabine in combination with docetaxel in patients with advanced pancreatic carcinoma (E1298). A trial of the eastern cooperative oncology group. Oncology 2004; 66: 303-309
36. Reni M, Cordio S, Milandri C, Passoni P, Bonetto E, Oliani C, Luppi G, Nicoletti R, Galli L, Bordonaro R, Passardi A, Zerbi A, Balzano G, Aldrighetti L, Staudacher C, Villa E, Di Carlo V. Gemcitabine versus cisplatin, epirubicin, fluorouracil, and gemcitabine in advanced pancreatic cancer: a randomised controlled multicentre phase III trial. Lancet Oncol 2005; 6: 369-376
37. Reni M, Cereda S, Bonetto E, Viganò MG, Passoni P, Zerbi A, Balzano G, Nicoletti R, Staudacher C, Di Carlo V. Dose-intense PEFG (cisplatin, epirubicin, 5-fluorouracil, gemcitabine) in advanced pancreatic adenocarcinoma. Cancer Chemother Pharmacol 2007; 59: 361-367
38. Ng SS, Tsao MS, Nicklee T, Hedley DW. 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: 777-783
39. Hidalgo M, Siu LL, Nemunaitis J, Rizzo J, Hammond LA, Takimoto C, Eckhardt SG, Tolcher A, Britten CD, Denis L, Ferrante K, Von Hoff DD, Silberman S, Rowinsky EK. Phase I and pharmacologic study of OSI-774, an epidermal growth factor receptor tyrosine kinase inhibitor, in patients with advanced solid malignancies. J Clin Oncol 2001; 19: 3267-3279
40. Moore MJ, Goldstein D, Hamm J, Figer A, Hecht JR, Gallinger S, Au HJ, Murawa P, Walde D, Wolff RA, Campos D, Lim R, Ding K, Clark G, Voskoglou-Nomikos T, Ptasynski M, Parulekar W. 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: 1960-1966
41. Xiong HQ, Rosenberg A, LoBuglio A, Schmidt W, Wolff RA, Deutsch J, Needle M, Abbruzzese JL. 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 2004; 22: 2610-2616
42. Lemoine NR, Hughes CM, Barton CM, Poulsom R, Jeffery RE, Klöppel G, Hall PA, Gullick WJ. The epidermal growth factor receptor in human pancreatic cancer. J Pathol 1992; 166: 7-12
43. Philip PA, Benedetti J, Fenoglio-Preiser C, Zalupski M, Lenz H, O'Reilly E, Wong R, Atkins J, Abruzzese J, Blanke C. Phase III study of gemcitabine plus cetuximab versus gemcitabine in patients with locally advanced or metastatic pancreatic adenocarcinoma: SWOG S0205 study. J Clin Oncol 2007; 25: No. 18S
44. Kindler HL, Friberg G, Stadler WM, Singh Da, Locker G, Nattam S, Kozloff M, Kasza K, Vokes EE. Bevacizumab (B) plus gemcitabine (G) in patient (pts) with advanced pancreatic cancer (PC): updated results of a multi-center phase II trial. J Clin Oncol 2004; 23 Suppl 15: 314 (abstract 4009)
45. Kindler HL, Niedzwiecki D, Hollis D, Oraefo E, Schrag D, Hurwitz H, McLeod HL, Mulcahy MF, Schilsky RL, Goldberg RM. A double-blind placebo-controlled, randomized phase III trial of gemcitabine plus bevacizumab versus gemcitabine plus placebo in patients with advanced pancreatic cancer: A preliminary analysis of Cancer and Leukemia Group B (CALGB) 80303. ASCO Gastrointestinal Cancers Symposium, 2007: Abstract 108
46. Vervenne W, Bennouna J, Humblet Y, Gill S, Moore MJ, Van Laethem J, Shang A, Cosaert J, Verslype C, Van Cutsem E. A randomized, double-blind, placebo (P) controlled, multicenter phase III trial to evaluate the efficacy and safety of adding bevacizumab (B) to erlotinib (E) and gemcitabine (G) in patients (pts) with metastatic pancreatic cancer. J Clin Oncol (Meeting Abstracts) 2008; 26: 4507
47. Fogelman DR, Varadhachary G, Xiong HQ, Chang DZ, Bullock SA, Ozer H, Wolff RA, Abbruzzese JL. Final results of a bi-institution phase II study of gemcitabine, oxaliplatin, and bevacizumab for advanced pancreatic cancer. ASCO Gastrointestinal Cancers Symposium, 2009: Abstract #182
48. Kim GP, Alberts SR, Oberg AL, Foster NR, Grothey A, Flynn PJ, Schaefer PL, Wiesenfeld M, Campbell D, Hedrick E. Phase II trial of bevacizumab, gemcitabine, and oxaliplatin in patients with metastatic pancreatic adenocarcinoma. ASCO Gastrointestinal Cancers Symposium, 2007: Abstract No. 159
49. Ko AH, Dicke K, Gurtler J, Keaton M, Lenz H, Firstenberg B, Zhang Y, Katz T, Youssoufian H. Phase II, randomized, open-label study of cetuximab and bevacizumab alone or in combination with fixed-dose rate (FDR) gemcitabine as firstline therapy for patients with metastatic adenocarcinoma of the pancreas (MPC). ASCO Gastrointestinal Cancers Symposium, 2009: Abstract #183
50. Kindler HL, Gangadhar T, Karrison T, Hochster HS, Moore MJ, Micetich K, Sun W, Catenacci DV, Stadler WM, Vokes EE. 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 (Meeting Abstracts) 2008; 26: 4502
51. Ducreux M, Mitry E, Ould-Kaci M, Boige V, Seitz JF, Bugat R, Breau JL, Bouché O, Etienne PL, Tigaud JM, Morvan F, Cvitkovic E, Rougier P. Randomized phase II study evaluating oxaliplatin alone, oxaliplatin combined with infusional 5-FU, and infusional 5-FU alone in advanced pancreatic carcinoma patients. Ann Oncol 2004; 15: 467-473
52. Mitry E, Dahan L, Ychou M, Arthaud J, Gasmi M, Raoul J, Mariette C, Phelip JM, Bedenne L, Seitz J, Federation Francophone de Cancerologie D. LV5FU2-cisplatin followed by gemcitabine or the reverse sequence in metastatic pancreatic cancer: Preliminary results of a randomized phase III trial (FFCD 0301). J Clin Oncol (Meeting Abstracts) 2008; 26: 4513
53. Löhr M, Haas S, Bechstein W, Bodoky G, Maerten A, Fischbach W, Lilla C, Mescheder A, Pap A, Fölsch UR. A phase II trial of cationic liposomal paclitaxel in combination with gemcitabine in patients with unresectable pancreatic cancer. ASCO Gastrointestinal Cancers Symposium, 2009: Abstract #LBA120
54. Heinemann V, Golf A, Seipelt G, Bauer J, Höhler T, Clemens M, Löhr JM, Stauch M, Lordick F, Hinke A. Capecitabine plus oxaliplatin (CapOx) versus capecitabine plus gemcitabine (CapGem) versus gemcitabine plus oxaliplatin (GemOx): A randomized phase II trial in advanced pancreatic cancer. J Clin Oncol 2005; 23: No. 16S (Abstract 4030)
55. Burtness BA, Powell ME, Berlin JD, Liles DK, Chapman AE, Mitchell EP, Benson AB. Phase II trial of irinotecan/docetaxel for advanced pancreatic cancer with randomization between irinotecan/docetaxel and irinotecan/docetaxel plus C225, a monoclonal antibody to the epidemal growth factor (EGFR). Eastern Cooperative Oncology (ECOG). J Clin Oncol 2007; 25: No. 18S (Abstract 4519)
56. O'Reilly EM, Niedzwiecki D, Hollis DR, Bekaii-Saab TS, Pluard T, Duffy A, Overcash F, Ivy SP, Goldberg RM. A phase II trial of sunitinib (S) in previously-treated pancreas adenocarcinoma (PAC), CALGB 80603. J Clin Oncol (Meeting Abstracts) 2008; 26: 4515
57. Iqbal S, Lenz HJ, Yang D, Ramanathan RK, Bahary N, Shibata S, Morgan RJ Jr, Gandara DR. A randomized phase II study of BAY 43-9006 in combination with gemcitabine in metastatic pancreatic carcinoma: A California Cancer Consortium study (CCC-P). J Clin Oncol (Meeting Abstracts) 2008; 26: 11082
58. Wolpin BM, Hezel AF, Ryan DP, Abrams TA, Meyerhardt JA, Blaszkowsky LS, Clark JW, Allen B, Regan EM, Fuchs CS. Phase II study of RAD001 in previously treated patients with metastatic pancreatic cancer. J Clin Oncol (Meeting Abstracts) 2008; 26: 4614
59. Cohen SJ, Ho L, Ranganathan S, Abbruzzese JL, Alpaugh RK, Beard M, Lewis NL, McLaughlin S, Rogatko A, Perez-Ruixo JJ, Thistle AM, Verhaeghe T, Wang H, Weiner LM, Wright JJ, Hudes GR, Meropol NJ. Phase II and pharmacodynamic study of the farnesyltransferase inhibitor R115777 as initial therapy in patients with metastatic pancreatic adenocarcinoma. J Clin Oncol 2003; 21: 1301-1306
60. Van Cutsem E, van de Velde H, Karasek P, Oettle H, Vervenne WL, Szawlowski A, Schoffski P, Post S, Verslype C, Neumann H, Safran H, Humblet Y, Perez Ruixo J, Ma Y, Von Hoff D. Phase III trial of gemcitabine plus tipifarnib compared with gemcitabine plus placebo in advanced pancreatic cancer. J Clin Oncol 2004; 22: 1430-1438
61. Evans JD, Stark A, Johnson CD, Daniel F, Carmichael J, Buckels J, Imrie CW, Brown P, Neoptolemos JP. A phase II trial of marimastat in advanced pancreatic cancer. Br J Cancer 2001; 85: 1865-1870
62. Bramhall SR, Rosemurgy A, Brown PD, Bowry C, Buckels JA. Marimastat as first-line therapy for patients with unresectable pancreatic cancer: a randomized trial. J Clin Oncol 2001; 19: 3447-3455
63. Bramhall SR, Schulz J, Nemunaitis J, Brown PD, Baillet M, Buckels JA. 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 Cancer 2002; 87: 161-167
64. Moore MJ, Hamm J, Dancey J, Eisenberg PD, Dagenais M, Fields A, Hagan K, Greenberg B, Colwell B, Zee B, Tu D, Ottaway J, Humphrey R, Seymour L. 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 2003; 21: 3296-3302
65. Kindler HL, Garbo LE, Stephenson J, Wiezorek J, Sabin T, Hsu M, Civoli F, Richards DA. Safety and efficacy of AMG 655 in combination with gemcitabine in patients with metastatic pancreatic cancer. ASCO Gastrointestinal Cancers Symposium, 2009: Abstract #192
66. Rothenberg ML, Moore MJ, Cripps MC, Andersen JS, Portenoy RK, Burris HA 3rd, Green MR, Tarassoff PG, Brown TD, Casper ES, Storniolo AM, Von Hoff DD. A phase II trial of gemcitabine in patients with 5-FU-refractory pancreas cancer. Ann Oncol 1996; 7: 347-353
67. Van Laethem J, Polus M, Marechal R, Demols A, Gay F, Marijken M, Hendlisz A, Peeters M. Gemcitabine and oxaliplatin in gemcitabine-refractory advanced pancreatic cancer: a phase II study. J Clin Oncol 2004; 22 Suppl 15: No. 14S (abstract 4119)
68. Pelzer U, Kubica K, Stieler J, Schwaner I, Heil G, Gorner M, Molle M, Hilbig A, Dorken B, Riess H, Oettle H. A randomized trial in patients with gemcitabine refractory pancreatic cancer. Final results of the CONKO 003 study. J Clin Oncol (Meeting Abstracts) 2008; 26: 4508
69. Jacobs AD, Burris HA, Rivkin S, Ritch PS, Eisenberg PD, Mettinger KL. A randomized phase III study of rubitecan (ORA) vs. best choice (BC) in 409 patients with refractory pancreatic cancer report from a North-American multi-center study. J Clin Oncol 2004; 22 Suppl 15: 315 (abstract 4013)
70. Cartwright TH, Cohn A, Varkey JA, Chen YM, Szatrowski TP, Cox JV, Schulz JJ. Phase II study of oral capecitabine in patients with advanced or metastatic pancreatic cancer. J Clin Oncol 2002; 20: 160-164
71. Xiong HQ, Varadhachary GR, Blais JC, Hess KR, Abbruzzese JL, Wolff RA. Phase 2 trial of oxaliplatin plus capecitabine (XELOX) as second-line therapy for patients with advanced pancreatic cancer. Cancer 2008; 113: 2046-2052