Does gemcitabine-based combination therapy improve the prognosis of unresectable pancreatic cancer?

World Journal of Gastroenterology

Volumn 18, Issue 35, 2012, Pages 4944-4958

  Sun, Chen ^a,b   Ansari, Daniel ^a,b   Andersson, Roland ^a,b   Wu, De Quan ^a  

^a THE SECOND AFFILIATED HOSPITAL OF HARBIN MEDICAL UNIVERSITY   (China)

^b LUND UNIVERSITY   (Sweden)

Author keywords

Combination therapy; Gemcitabine; Meta analysis; Outcome; Pancreatic cancer

Indexed keywords

ANTINEOPLASTIC AGENT; AXITINIB; BEVACIZUMAB; CA 994; CAMPTOTHECIN; CAPECITABINE; CETUXIMAB; CILENGITIDE; CISPLATIN; ENZASTAURIN; ERLOTINIB; EXATECAN; FLUOROPYRIMIDINE; FLUOROURACIL; GEMCITABINE; IRINOTECAN; MARIMASTAT; OXALIPLATIN; PEMETREXED; PLATINUM; TIPIFARNIB; UNCLASSIFIED DRUG;

ADVANCED CANCER; ANEMIA; ARTICLE; CANCER PROGNOSIS; CANCER SURVIVAL; DIARRHEA; DRUG EFFICACY; HUMAN; INOPERABLE CANCER; META ANALYSIS; METASTASIS; MONOTHERAPY; NEUTROPENIA; OVERALL SURVIVAL; PANCREAS CANCER; PROGRESSION FREE SURVIVAL; THROMBOCYTOPENIA; TREATMENT RESPONSE; UNRESECTABLE PANCREATIC CANCER; VOMITING;

EID: 84867800359     PISSN: 10079327     EISSN: 22192840     Source Type: Journal    
DOI: 10.3748/wjg.v18.i35.4944     Document Type: Article

References (54)

1. Parkin DM, Bray FI, Devesa SS. Cancer burden in the year 2000. The global picture. Eur J Cancer 2001; 37 Suppl 8: S4-66
2. Jemal A, Siegel R, Xu J, Ward E. Cancer statistics, 2010. CA Cancer J Clin 2010; 60: 277-300
3. Fryer RA, Galustian C, Dalgleish AG. Recent advances and developments in treatment strategies against pancreatic cancer. Curr Clin Pharmacol 2009; 4: 102-112
4. Jonckheere N, Fauquette V, Stechly L, Saint-Laurent N, Aubert S, Susini C, Huet G, Porchet N, Van Seuningen I, Pigny P. Tumour growth and resistance to gemcitabine of pancreatic cancer cells are decreased by AP-2alpha overexpression. Br J Cancer 2009; 101: 637-644
5. O'Reilly EM, Abou-Alfa GK. Cytotoxic therapy for advanced pancreatic adenocarcinoma. Semin Oncol 2007; 34: 347-353
6. Yeo CJ, Cameron JL. Improving results of pancreaticoduodenectomy for pancreatic cancer. World J Surg 1999; 23: 907-912
7. Andersson R, Aho U, Nilsson BI, Peters GJ, Pastor-Anglada M, Rasch W, Sandvold ML. Gemcitabine chemoresistance in pancreatic cancer: molecular mechanisms and potential solutions. Scand J Gastroenterol 2009; 44: 782-786
8. Jadad AR, Moore RA, Carroll D, Jenkinson C, Reynolds DJ, Gavaghan DJ, McQuay HJ. Assessing the quality of reports of randomized clinical trials: is blinding necessary? Control Clin Trials 1996; 17: 1-12
9. Miller AB, Hoogstraten B, Staquet M, Winkler A. Reporting results of cancer treatment. Cancer 1981; 47: 207-214
10. Therasse P, Arbuck SG, Eisenhauer EA, Wanders J, Kaplan RS, Rubinstein L, Verweij J, Van Glabbeke M, van Oosterom AT, Christian MC, Gwyther SG. New guidelines to evaluate the response to treatment in solid tumors. European Organization for Research and Treatment of Cancer, National Cancer Institute of the United States, National Cancer Institute of Canada. J Natl Cancer Inst 2000; 92: 205-216
11. Case LD, Kimmick G, Paskett ED, Lohman K, Tucker R. Interpreting measures of treatment effect in cancer clinical trials. Oncologist 2002; 7: 181-187
12. Higgins JP, Thompson SG, Deeks JJ, Altman DG. Measuring inconsistency in meta-analyses. BMJ 2003; 327: 557-560
13. Higgins JP, Thompson SG. Quantifying heterogeneity in a meta-analysis. Stat Med 2002; 21: 1539-1558
14. Huedo-Medina TB, Sánchez-Meca J, Marín-Martínez F, Botella J. Assessing heterogeneity in meta-analysis: Q statistic or I2 index? Psychol Methods 2006; 11: 193-206
15. 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
16. 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. 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 2009; 27: 3778-3785
17. 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
18. 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
19. Colucci G, Labianca R, Di Costanzo F, Gebbia V, Cartenì G, Massidda B, Dapretto E, Manzione L, Piazza E, Sannicolò M, Ciaparrone M, Cavanna L, Giuliani F, Maiello E, Testa A, Pederzoli P, Falconi M, Gallo C, Di Maio M, Perrone F. 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: 1645-1651
20. Kulke MH, Tempero MA, Niedzwiecki D, Hollis DR, Kindler HL, Cusnir M, Enzinger PC, Gorsch SM, Goldberg RM, Mayer RJ. Randomized phase II study of gemcitabine administered at a fixed dose rate or in combination with cisplatin, docetaxel, or irinotecan in patients with metastatic pancreatic cancer: CALGB 89904. J Clin Oncol 2009; 27: 5506-5512
21. Berlin JD, Catalano P, Thomas JP, Kugler JW, Haller DG, Benson AB. 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
22. Herrmann R, Bodoky G, Ruhstaller T, Glimelius B, Bajetta E, Schüller J, Saletti P, Bauer J, Figer A, Pestalozzi B, Köhne CH, Mingrone W, Stemmer SM, Tàmas K, Kornek GV, Koeberle D, Cina S, Bernhard J, Dietrich D, Scheithauer W. 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: 2212-2217
23. 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
24. 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
25. 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
26. Di Costanzo F, Carlini P, Doni L, Massidda B, Mattioli R, Iop A, Barletta E, Moscetti L, Recchia F, Tralongo P, Gasperoni S. Gemcitabine with or without continuous infusion 5-FU in advanced pancreatic cancer: a randomised phase II trial of the Italian oncology group for clinical research (GOIRC). Br J Cancer 2005; 93: 185-189
27. Abou-Alfa GK, Letourneau R, Harker G, Modiano M, Hurwitz H, Tchekmedyian NS, Feit K, Ackerman J, De Jager RL, Eckhardt SG, O'Reilly EM. Randomized phase III study of exatecan and gemcitabine compared with gemcitabine alone in untreated advanced pancreatic cancer. J Clin Oncol 2006; 24: 4441-4447
28. Stathopoulos GP, Syrigos K, Aravantinos G, Polyzos A, Papakotoulas P, Fountzilas G, Potamianou A, Ziras N, Boukovinas J, Varthalitis J, Androulakis N, Kotsakis A, Samonis G, Georgoulias V. 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: 587-592
29. Rocha Lima CM, Green MR, Rotche R, Miller WH, 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
30. Oettle H, Richards D, Ramanathan RK, van Laethem JL, Peeters M, Fuchs M, Zimmermann A, John W, Von Hoff D, Arning M, Kindler HL. A phase III trial of pemetrexed plus gemcitabine versus gemcitabine in patients with unresectable or metastatic pancreatic cancer. Ann Oncol 2005; 16: 1639-1645
31. 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
32. Richards DA, Boehm KA, Waterhouse DM, Wagener DJ, Krishnamurthi SS, Rosemurgy A, Grove W, Macdonald K, Gulyas S, Clark M, Dasse KD. Gemcitabine plus CI-994 offers no advantage over gemcitabine alone in the treatment of patients with advanced pancreatic cancer: results of a phase II randomized, double-blind, placebo-controlled, multicenter study. Ann Oncol 2006; 17: 1096-1102
33. Richards DA, Kuefler PR, Becerra C, Wilfong LS, Gersh RH, Boehm KA, Zhan F, Asmar L, Myrand SP, Hozak RR, Zhao L, Gill JF, Mullaney BP, Obasaju CK, Nicol SJ. Gemcitabine plus enzastaurin or single-agent gemcitabine in locally advanced or metastatic pancreatic cancer: results of a phase II, randomized, noncomparative study. Invest New Drugs 2011; 29: 144-153
34. Friess H, Langrehr JM, Oettle H, Raedle J, Niedergethmann M, Dittrich C, Hossfeld DK, Stöger H, Neyns B, Herzog P, Piedbois P, Dobrowolski F, Scheithauer W, Hawkins R, Katz F, Balcke P, Vermorken J, van Belle S, Davidson N, Esteve AA, Castellano D, Kleeff J, Tempia-Caliera AA, Kovar A, Nippgen J. A randomized multi-center phase II trial of the angiogenesis inhibitor Cilengitide (EMD 121974) and gemcitabine compared with gemcitabine alone in advanced unresectable pancreatic cancer. BMC Cancer 2006; 6: 285
35. Kindler HL, Ioka T, Richel DJ, Bennouna J, Létourneau R, Okusaka T, Funakoshi A, Furuse J, Park YS, Ohkawa S, Springett GM, Wasan HS, Trask PC, Bycott P, Ricart AD, Kim S, Van Cutsem E. Axitinib plus gemcitabine versus placebo plus gemcitabine in patients with advanced pancreatic adenocarcinoma: a double-blind randomised phase 3 study. Lancet Oncol 2011; 12: 256-262
36. Kindler HL, Niedzwiecki D, Hollis D, Sutherland S, Schrag D, Hurwitz H, Innocenti F, Mulcahy MF, O'Reilly E, Wozniak TF, Picus J, Bhargava P, Mayer RJ, Schilsky RL, Goldberg RM. Gemcitabine plus bevacizumab compared with gemcitabine plus placebo in patients with advanced pancreatic cancer: phase III trial of the Cancer and Leukemia Group B (CALGB 80303). J Clin Oncol 2010; 28: 3617-3622
37. Philip PA, Benedetti J, Corless CL, Wong R, O'Reilly EM, Flynn PJ, Rowland KM, Atkins JN, Mirtsching BC, Rivkin SE, Khorana AA, Goldman B, Fenoglio-Preiser CM, Abbruzzese JL, Blanke CD. Phase III study comparing gemcitabine plus cetuximab versus gemcitabine in patients with advanced pancreatic adenocarcinoma: Southwest Oncology Group-directed intergroup trial S0205. J Clin Oncol 2010; 28: 3605-3610
38. 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
39. 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
40. Eckhardt SG, De Porre P, Smith D, Maurel J, Steward WP, Bouche O, van de Velde H, Michiels B, Bugat R. Patientreported outcomes as a component of the primary endpoint in a double-blind, placebo-controlled trial in advanced pancreatic cancer. J Pain Symptom Manage 2009; 37: 135-143
41. Spano JP, Chodkiewicz C, Maurel J, Wong R, Wasan H, Barone C, Létourneau R, Bajetta E, Pithavala Y, Bycott P, Trask P, Liau K, Ricart AD, Kim S, Rixe O. Efficacy of gemcitabine plus axitinib compared with gemcitabine alone in patients with advanced pancreatic cancer: an open-label randomised phase II study. Lancet 2008; 371: 2101-2108
42. Burris HA, 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
43. Hu J, Zhao G, Wang HX, Tang L, Xu YC, Ma Y, Zhang FC. A meta-analysis of gemcitabine containing chemotherapy for locally advanced and metastatic pancreatic adenocarcinoma. J Hematol Oncol 2011; 4: 11
44. Xie DR, Liang HL, Wang Y, Guo SS, Yang Q. Meta-analysis on inoperable pancreatic cancer: a comparison between gemcitabine-based combination therapy and gemcitabine alone. World J Gastroenterol 2006; 12: 6973-6981
45. Xie de R, Liang HL, Wang Y, Guo SS. Meta-analysis of inoperable pancreatic cancer: gemcitabine combined with cisplatin versus gemcitabine alone. Chin J Dig Dis 2006; 7: 49-54
46. Hagmann W, Jesnowski R, Löhr JM. Interdependence of gemcitabine treatment, transporter expression, and resistance in human pancreatic carcinoma cells. Neoplasia 2010; 12: 740-747
47. Hwang RF, Moore T, Arumugam T, Ramachandran V, Amos KD, Rivera A, Ji B, Evans DB, Logsdon CD. Cancerassociated stromal fibroblasts promote pancreatic tumor progression. Cancer Res 2008; 68: 918-926
48. Olive KP, Jacobetz MA, Davidson CJ, Gopinathan A, Mc-Intyre D, Honess D, Madhu B, Goldgraben MA, Caldwell ME, Allard D, Frese KK, Denicola G, Feig C, Combs C, Winter SP, Ireland-Zecchini H, Reichelt S, Howat WJ, Chang A, Dhara M, Wang L, Rückert F, Grützmann R, Pilarsky C, Izeradjene K, Hingorani SR, Huang P, Davies SE, Plunkett W, Egorin M, Hruban RH, Whitebread N, McGovern K, Adams J, Iacobuzio-Donahue C, Griffiths J, Tuveson DA. Inhibition of Hedgehog signaling enhances delivery of chemotherapy in a mouse model of pancreatic cancer. Science 2009; 324: 1457-1461
49. Shah AN, Summy JM, Zhang J, Park SI, Parikh NU, Gallick GE. Development and characterization of gemcitabineresistant pancreatic tumor cells. Ann Surg Oncol 2007; 14: 3629-3637
50. Vandana M, Sahoo SK. Long circulation and cytotoxicity of PEGylated gemcitabine and its potential for the treatment of pancreatic cancer. Biomaterials 2010; 31: 9340-9356
51. Sultana A, Tudur Smith C, Cunningham D, Starling N, Neoptolemos JP, Ghaneh P. Meta-analyses of chemotherapy for locally advanced and metastatic pancreatic cancer: results of secondary end points analyses. Br J Cancer 2008; 99: 6-13
52. 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
53. Bria E, Milella M, Gelibter A, Cuppone F, Pino MS, Ruggeri EM, Carlini P, Nisticò C, Terzoli E, Cognetti F, Giannarelli D. Gemcitabine-based combinations for inoperable pancreatic cancer: have we made real progress? A meta-analysis of 20 phase 3 trials. Cancer 2007; 110: 525-533
54. Sultana A, Smith CT, Cunningham D, Starling N, Neoptolemos JP, Ghaneh P. Meta-analyses of chemotherapy for locally advanced and metastatic pancreatic cancer. J Clin Oncol 2007; 25: 2607-2615