Gemcitabine in Combination with a Second Cytotoxic Agent in the First-Line Treatment of Locally Advanced or Metastatic Pancreatic Cancer: a Systematic Review and Meta-Analysis

Targeted Oncology

Volumn 12, Issue 3, 2017, Pages 309-321

  Zhang, Xiu Wei ^a   Ma, Yu Xiang ^a   Sun, Yang ^a   Cao, Yu Bo ^a   Li, Qin ^a   Xu, Chong An ^a  

^a CHINA MEDICAL UNIVERSITY   (China)

Author keywords

[No Author keywords available]

Indexed keywords

CAPECITABINE; CISPLATIN; CYTOTOXIC AGENT; DNA TOPOISOMERASE INHIBITOR; DOCETAXEL; EXATECAN; FLUOROPYRIMIDINE; FLUOROURACIL; GEMCITABINE; GIMERACIL PLUS OTERACIL POTASSIUM PLUS TEGAFUR; IRINOTECAN; OXALIPLATIN; PACLITAXEL; PEMETREXED; PLATINUM COMPLEX; TAXOID; UFT; ANTINEOPLASTIC AGENT; DEOXYCYTIDINE;

ADULT; ADVANCED CANCER; ANEMIA; ANTINEOPLASTIC ACTIVITY; CANCER COMBINATION CHEMOTHERAPY; CANCER SURVIVAL; CONTINUOUS INFUSION; DIARRHEA; DRUG EFFICACY; DRUG RESPONSE; DRUG SAFETY; DRUG TREATMENT FAILURE; FATIGUE; FEMALE; HUMAN; INOPERABLE CANCER; LEUKOPENIA; MAJOR CLINICAL STUDY; MALE; META ANALYSIS; METASTASIS POTENTIAL; METASTATIC PANCREAS CANCER; MONOTHERAPY; NEUTROPENIA; OVERALL SURVIVAL; PANCREAS CANCER; PRIORITY JOURNAL; PROGRESSION FREE SURVIVAL; REVIEW; SYSTEMATIC REVIEW; THROMBOCYTOPENIA; TIME TO TREATMENT; VOMITING; ANALOGS AND DERIVATIVES; CANCER STAGING; METASTASIS; MORTALITY; PANCREAS TUMOR; RANDOMIZED CONTROLLED TRIAL (TOPIC); SURVIVAL ANALYSIS;

ANTINEOPLASTIC COMBINED CHEMOTHERAPY PROTOCOLS; DEOXYCYTIDINE; HUMANS; NEOPLASM METASTASIS; NEOPLASM STAGING; NEUTROPENIA; PANCREATIC NEOPLASMS; RANDOMIZED CONTROLLED TRIALS AS TOPIC; SURVIVAL ANALYSIS; TAXOIDS;

EID: 85016091014     PISSN: 17762596     EISSN: 1776260X     Source Type: Journal    
DOI: 10.1007/s11523-017-0486-5     Document Type: Review

References (71)

1. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2015. CA Cancer J Clin. 2015;65:5–29.
2. Rahib L, Smith BD, Aizenberg R, et al. Projecting cancer incidence and deaths to 2030: the unexpected burden of thyroid, liver, and pancreas cancers in the United States. Cancer Res. 2014;74(14):2913–21.
3. Fryer RA, Galustian C, Dalgleish AG. Recent advances and developments in treatment strategies against pancreatic cancer. Curr Clin Pharmacol. 2009;4:102–12.
4. Hackert T, Buchler MW. Pancreatic cancer: advances in treatment, results and limitations. Dig Dis. 2013;31(1):51–6.
5. Rosewicz S, Wiedenmann B. Pancreatic carcinoma. Lancet. 1997;349(9050):485–9.
6. Hidalgo M. Pancreatic cancer. N Engl J Med. 2010;362:1605–17.
7. Stathis A, Moore MJ. Advanced pancreatic carcinoma: current treatment and future challenges. Nat Rev Clin Oncol. 2010;7(3):163–72.
8. Yeo CJ, Cameron JL. Improving results of pancreaticoduodenectomy for pancreatic cancer. World J Surg. 1999;23(9):907–12.
9. Burris 3rd 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. Clin Oncol. 1997;15:2403–13.
10. NCCN guidelines for pancreatic cancer. [Accessed January 30, 2016]. Available from:http://www.nccn.org/professionals/physician_gls/pdf/pancreatic.pdf.
11. Rocha Lima CM, Flores AM. Gemcitabine doublets in advanced pancreatic cancer: should we move on? J Clin Oncol. 2006;24(3):327–9.
12. Welch SA, Moore MJ. Combination chemotherapy in advanced pancreatic cancer: time to raise the white flag? J Clin Oncol. 2007;25(16):2159–61.
13. Sun C, Ansari D, Andersson R, et al. Does gemcitabine-based combination therapy improve the prognosis of unresectable pancreatic cancer? World J Gastroenterol. 2012;18(35):4944–58.
14. Ciliberto D, Botta B, Correale P, et al. Role of gemcitabine-based combination therapy in the management of advanced pancreatic cancer: a meta-analysis of randomised trials. Eur J Cancer. 2013;49:593–603.
15. Von Hoff DD, Ervin T, Arena FP, Chiorean EG, et al. Increased survival in pancreatic cancer with nab-paclitaxel plus gemcitabine. N Engl J Med. 2013;369(18):1691–703.
16. Conroy T, Desseigne F, Ychou M, et al. FOLFIRINOX versus gemcitabine for metastatic pancreatic cancer. N Engl J Med. 2011;364:1817.
17. Jadad AR, Moore RA, Carroll D, Jenkinson C, et al. Assessing the quality of reports of randomized clinical trials: is blinding necessary? Control Clin Trials. 1996;17(1):1–12.
18. Parmar MK, Torri V, Stewart L. Extracting summary statistics to perform meta-analyses of the published literature for survival endpoints. Stat Med. 1998;17:2815–34.
19. Tierney JF, Stewart LA, Ghersi D, et al. Practical methods for incorporating summary time-to-event data into meta-analysis. Trials. 2007;8:16.
20. DerSimonian R, Levine RJ. Resolving discrepancies between a meta-analysis and a subsequent large controlled trial. JAMA, J Am Med Assoc. 1999;282(7):664–70.
21. DerSimonian R, Kacker R. Random-effects model for meta-analysis of clinical trials: an update. Contemp Clin Trials. 2007;28(2):105–14.
22. Boston RC, Sumner AE. STATA: a statistical analysis system for examining biomedical data. Adv Exp Med Biol. 2003;537:353–69.
23. Omuro Y, Ikari T, Ishii H, et al. A randomized phase II study of gemcitabine plus S-1 versus gemcitabine alone in patients with unresectable pancreatic cancer. J Clin Oncol. 2011;29 Suppl 15:4029.
24. Vogel A, Penenberg D, McGovern D, et al. 2358 Efficacy and safety of nab-Paclitaxel (nab-P) plus gemcitabine (Gem) vs gem alone in patients (Pts) with metastatic pancreatic cancer (MPC) treated to progressive disease (PD) in the phase III MPACT trial. Eur J Cancer. 2015;51:S455.
25. Palacio S, Akunyili II, Ernani V, et al. Gemcitabine (Gem) and nab-paclitaxel (nab-P) in patients (pts) with refractory advanced pancreatic cancer. J Clin Oncol. 2015;33(3):413.
26. Riess H, Helm A, Niedergethmann M, et al. A randomised, prospective, multicenter, phase III trial of gemcitabine, 5-fluorouracil (5-FU), folinic acid vs. gemcitabine alone in patients with advanced pancreatic cancer. Cancer J. 2010;8(3):255–62.
27. O’ Reilly EM, Aboualfa GK, Letourneau R, et al. 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;22 Suppl 14:4006.
28. 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;26:3695–701.
29. Berlin JD, Catalano P, Thomas JP, et al. 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(20):3270–5.
30. 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.
31. Ohkawa S. Randomized controlled trial of gemcitabine in combination with UFT versus gemcitabine alone in patients with advanced pancreatic cancer. J Clin Oncol. 2004;22 Suppl 14:4131.
32. 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.
33. 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. Clin Oncol. 2007;25:2212–7.
34. Cunningham D, Chau I, Stocken D, et al. Phase III randomized comparison of gemcitabine versus gemcitabine plus capecitabine in patients with advanced pancreatic cancer. J Clin Oncol. 2009;27(33):5513–8.
35. Ioka T, Ikeda M, Ohkawa S, et al. Randomized phase III study of gemcitabine plus S-1 (GS) versus S-1 versus gemcitabine (GEM) in unresectable advanced pancreatic cancer (PC) in Japan and Taiwan: GEST study. J Clin Oncol. 2011;29 Suppl 15:4007.
36. Nakai Y, Isayama H, Sasaki T, et al. A multicentre randomised phase II trial of gemcitabine alone vs gemcitabine and S-1 combination therapy in advanced pancreatic cancer: GEMSAP study. Br J Cancer. 2012;106(12):1934–9.
37. Ozaka M. et al.Randomized phase II study of gemcitabine and S-1 combination versus gemcitabine alone in the treatment of unresectable advanced pancreatic cancer (Japan Clinical Cancer Research Organization PC-01 study). Cancer Chemother Pharmacol. 2012;69(5):1197–204.
38. 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(13):1640–8.
39. Sudo K, Ishihara T, Hirata N, et al. Randomized controlled study of gemcitabine plus S-1 combination chemotherapy versus gemcitabine for unresectable pancreatic cancer. Cancer Chemother Pharmacol. 2014;73(2):389–96.
40. 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(15):3509–16.
41. Poplin E, Feng YJ. 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(23):3778–85.
42. 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. Cancer. 2002;94:902–10.
43. Wang X, Ni Q, et al. Gemcitabine or gemcitabine plus cisplatin for in 42 patients with locally advanced or metastatic pancreatic cancer. Zhonghua Zhong Liu Za Zhi. 2002;24(4):404–7.
44. Viret F, Ychou M, Lepille D, et al. Gemcitabine in combination with cisplatin (GP) versus gemcitabine (G) alone in the treatment of locally advanced or metastatic pancreatic cancer: Final results of a multicenter randomized phase II study. J Clin Oncol. 2004;22 Suppl 14:4118.
45. Li CP, Chao Y. A prospective randomized trial of gemcitabine alone or gemcitabine + cisplatin in the treatment of metastatic pancreatic cancer. J Clin Oncol. 2004;22 Suppl 14:4144.
46. 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. 2006;24(24):3946–52.
47. 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.
48. Chao Y, Wu CY, Wang JP. et al.A randomized controlled trial of gemcitabine plus cisplatin versus gemcitabine alone in the treatment of metastatic pancreatic cancer. Cancer Chemother Pharmacol. 2013;72(3):637–42.
49. Kulke MH, Tempero MA, Niedzwiecki D, et al. Randomized phase II study of docetaxel, or irinotecan in patients with metastatic pancreatic cancer:CALGB 89904. J Clin Oncol. 2009;27:5506–12.
50. Lohr JM, Haas SL, Bechstein WO, et al. Cationic liposomal paclitaxel plus gemcitabine or gemcitabine alone in patients with advanced pancreatic cancer: randomized controlled phaseIItrial. Ann Oncol. 2012;23:1214–22.
51. Abou-Alfa GK, Letourneau R, Harker G, et al. Randomized phase III study of exatecan and gemcitabine compared with gemcitabine alone in untreated advanced pancreatic cancer. J Clin Oncol. 2006;24(27):4441–7.
52. Rocha Lima CM, Green MR, Rotche R, Miller Jr WH, 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. 2004;22(18):3776–83.
53. Stathopoulos GP, Syrigos KG, Polyzos A, 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 Cancer. 2006;95(5):587–92.
54. 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;16:1639–45.
55. Burris 3rd HA. Recent updates on the role of chemotherapy in pancreatic cancer. Semin Oncol. 2005;32(4 Suppl 6):S1–3.
56. Bria E, Milella M, et al. Gemcitabine-based combinations for inoperable pancreatic cancer: have we made real progress? Cancer. 2007;110(3):525–33.
57. de Xie 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.
58. Petrelli F, Coinu A, Borgonovo K, et al. Polychemotherapy or gemcitabine in advanced pancreatic cancer: A meta-analysis. Dig Liver Dis. 2014;46(5):452–9.
59. Hu J, Zhao G, Wang HX, et al. A meta-analysis of gemcitabine containing chemotherapy for locally advanced and metastatic pancreatic adenocarcinoma. J Hematol Oncol. 2011;4(2):11.
60. Hoff PM, Cassidy J, Schmoll HJ. The evolution of fluoropyrimidine therapy: from intravenous to oral. Oncologist. 2001;6 Suppl 4:3–11.
61. Yardley DA. Nab-paclitaxel mechanisms of action and delivery. J Control Release. 2013;170:365–72.
62. Von Hoff DD, Ramanathan RK. Gemcitabine plus nab-pacltaxel is an active regimen in patients with advanced pancreatic cancer: a phase I/II trial. J Clin Oncol. 2011;29(34):4548–54.
63. Heinemann V, Boeck S, 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.
64. Reni M, Cordio S, Milandri C, et al. Gemcitabine versus cisplatin, epirubicin, fluorouracil, and gemcitabine in advanced pancreatic cancer: a randomised controlled multicentre phase III trial. Lancet Oncol. 2005;6:369–76.
65. Fine RL, Fogelman DR, Schreibman SM,et al. The gemcitabine, docetaxel, and capecitabine (GTX) regimen for metastatic pancreatic cancer: a retrospective analysis.Cancer Chemother Pharmacol. 2008;61:167–175.
66. De Jesus-Acosta A, Oliver GR, Blackford A,et al. A multicenter analysis of GTX chemotherapy in patients with locally advanced and metastatic pancreatic adenocarcinoma. Cancer Chemother Pharmacol. 2012;69:415–424.
67. Yang ZY, Yuan JQ, et al. Gemcitabine plus erlotinib for advanced pancreatic cancer: a systematic review with meta-analysis. Plos One. 2013;8(3):e57528.
68. 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 Leukemia Group B(CALGB80303). J Clin Oncol. 2010;28:3617–22.
69. Philip PA, Benedetti J, Corless CL, et al. 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;28:3605–10.
70. Gonçalves A, Gilabert M, François E, et al. BAYPAN study: a double blind phase III randomized trial comparing gemcitabine plus sorafenib and gemcitabine plus placebo in patients with advanced pancreatic cancer. Ann Oncol. 2012;23:2799–805.
71. Boeck S, Hinke A, et al. Importance of performance status for treatment outcome in advanced pancreatic cancer. World J Gastroenterol. 2007;13(2):224–7.