Skip to main content
Top
Published in: Tumor Biology 11/2014

01-11-2014 | Research Article

Outcome of gemcitabine plus molecular targeted agent for treatment of pancreatic cancer: a meta-analysis of prospective phase III studies

Authors: Lin Chen, Ming Zhang, Shuchun Luo

Published in: Tumor Biology | Issue 11/2014

Login to get access

Abstract

The aim of this study is to assess the clinical outcome of gemcitabine (GEM) plus molecular targeted agents (MTAs) for treatment of pancreatic cancer, in the purpose of providing fundamental data for clinical practice. Databases like PubMed, EMBASE, and MEDLINE, EMBASE and Cochrane Library were searched to retrieve phase III clinical randomized controlled trials related to GEM plus MTAs for pancreatic cancer (up to Oct 2013). Literatures were independently screened by two researchers according to the inclusion and exclusion criteria. Data were extracted and analyzed by using Stata 11.0 software. Total, 11 studies were included, involving 5,451 participants who were divided into GEM plus MTAs group (n = 2,729) and GEM plus placebo group (n = 2,722). There was no significant difference in overall survival, progression-free survival, response rate, complete response, partial response, and clinical benefit rate between two groups. Compared with GEM plus placebo group, stable disease of GEM plus MTAs group was significantly increased (risk ratios (RRs) = 1.14, 95 % confidence interval (CI) 1.04–1.21, P = 0.003). Further subgroup analysis indicated that GEM plus epidermal growth factor receptor (EGFR) inhibitor use induced higher response rate and clinical benefit rate than GEM plus placebo group (RRs = 1.19, 95 % CI 1.09–1.31, P = 0.000; RR = 1.18, 95 % CI 1.09–1.27, P = 0.000). In addition, no significant difference in 3–4 grade adverse reactions (incidence, anemia rate, neutropenia rate, and thrombocytopenia rate) was identified between two groups. GEM plus MTAs may be effective and safe for stabilizing patients suffering advanced pancreatic cancer, especially EGFR inhibitor.
Literature
1.
2.
go back to reference Holly EA, Chaliha I, Bracci PM, Gautam M. Signs and symptoms of pancreatic cancer: a population-based case-control study in the San Francisco Bay area. Clin Gastroenterol Hepatol. 2004;2:510–7.PubMedCrossRef Holly EA, Chaliha I, Bracci PM, Gautam M. Signs and symptoms of pancreatic cancer: a population-based case-control study in the San Francisco Bay area. Clin Gastroenterol Hepatol. 2004;2:510–7.PubMedCrossRef
3.
go back to reference Colucci G, Labianca R, Di Costanzo F, Gebbia V, Cartenì G, Massidda B, 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;28:1645–51.PubMedCrossRef Colucci G, Labianca R, Di Costanzo F, Gebbia V, Cartenì G, Massidda B, 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;28:1645–51.PubMedCrossRef
4.
go back to reference Alone C. Controversies in the adjuvant treatment of pancreatic adenocarcinoma. JOP. 2007;8:545–52. Alone C. Controversies in the adjuvant treatment of pancreatic adenocarcinoma. JOP. 2007;8:545–52.
5.
go back to reference Burris H, Moore MJ, Andersen J, Green MR, Rothenberg ML, Modiano MR. 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;15:2403–13.PubMed Burris H, Moore MJ, Andersen J, Green MR, Rothenberg ML, Modiano MR. 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;15:2403–13.PubMed
6.
go back to reference Eltawil KM, Renfrew PD, Molinari M. Meta-analysis of phase III randomized trials of molecular targeted therapies for advanced pancreatic cancer. HPB (Oxford). 2012;14:260–8.CrossRef Eltawil KM, Renfrew PD, Molinari M. Meta-analysis of phase III randomized trials of molecular targeted therapies for advanced pancreatic cancer. HPB (Oxford). 2012;14:260–8.CrossRef
7.
go back to reference Cao Y, Wu L, Tan A, Liu L, Liao C, Gao F. Meta-analysis of randomized trials: evaluation of benefit of gemcitabine-based molecular targeted therapy for inoperable pancreatic cancer. Pancreas. 2010;39:253–5.PubMedCrossRef Cao Y, Wu L, Tan A, Liu L, Liao C, Gao F. Meta-analysis of randomized trials: evaluation of benefit of gemcitabine-based molecular targeted therapy for inoperable pancreatic cancer. Pancreas. 2010;39:253–5.PubMedCrossRef
8.
go back to reference Ciliberto D, Botta C, Correale P, Rossi M, Caraglia M, Tassone 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.PubMedCrossRef Ciliberto D, Botta C, Correale P, Rossi M, Caraglia M, Tassone 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.PubMedCrossRef
9.
10.
go back to reference Moore MJ, Goldstein D, Hamm J, Figer A, Hecht JR, Gallinger S, 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. 2007;25:1960–6.PubMedCrossRef Moore MJ, Goldstein D, Hamm J, Figer A, Hecht JR, Gallinger S, 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. 2007;25:1960–6.PubMedCrossRef
11.
go back to reference Rougier P, Riess H, Manges R, Karasek P, Humblet Y, Barone C, et al. Randomised, placebo-controlled, double-blind, parallel-group phase III study evaluating aflibercept in patients receiving first-line treatment with gemcitabine for metastatic pancreatic cancer. Eur J Cancer. 2013;49:2633–42.PubMedCrossRef Rougier P, Riess H, Manges R, Karasek P, Humblet Y, Barone C, et al. Randomised, placebo-controlled, double-blind, parallel-group phase III study evaluating aflibercept in patients receiving first-line treatment with gemcitabine for metastatic pancreatic cancer. Eur J Cancer. 2013;49:2633–42.PubMedCrossRef
12.
go back to reference Kindler HL, Ioka T, Richel DJ, Bennouna J, Létourneau R, Okusaka T, et al. Axitinib plus gemcitabine versus placebo plus gemcitabine in patients with advanced pancreatic adenocarcinoma: a double-blind randomised phase 3 study. Lancet Oncol. 2011;12:256–62.PubMedCrossRef Kindler HL, Ioka T, Richel DJ, Bennouna J, Létourneau R, Okusaka T, et al. Axitinib plus gemcitabine versus placebo plus gemcitabine in patients with advanced pancreatic adenocarcinoma: a double-blind randomised phase 3 study. Lancet Oncol. 2011;12:256–62.PubMedCrossRef
13.
go back to reference Jadad AR, Moore RA, Carroll D, Jenkinson C, Reynolds DJM, Gavaghan DJ, et al. Assessing the quality of reports of randomized clinical trials: is blinding necessary? Control Clin Trials. 1996;17:1–12.PubMedCrossRef Jadad AR, Moore RA, Carroll D, Jenkinson C, Reynolds DJM, Gavaghan DJ, et al. Assessing the quality of reports of randomized clinical trials: is blinding necessary? Control Clin Trials. 1996;17:1–12.PubMedCrossRef
14.
go back to reference Begg CB, Mazumdar M. Operating characteristics of a rank correlation test for publication bias. Biometrics. 1994;50:1088–101.PubMedCrossRef Begg CB, Mazumdar M. Operating characteristics of a rank correlation test for publication bias. Biometrics. 1994;50:1088–101.PubMedCrossRef
16.
go back to reference Bramhall S, Schulz J, Nemunaitis J, Brown P, Baillet M, Buckels J. 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;87:161–7.PubMedCentralPubMedCrossRef Bramhall S, Schulz J, Nemunaitis J, Brown P, Baillet M, Buckels J. 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;87:161–7.PubMedCentralPubMedCrossRef
17.
go back to reference Van Cutsem E, Van de Velde H, Karasek P, Oettle H, Vervenne W, Szawlowski A, 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.PubMedCrossRef Van Cutsem E, Van de Velde H, Karasek P, Oettle H, Vervenne W, Szawlowski A, 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.PubMedCrossRef
18.
go back to reference Oettle H, Richards D, Ramanathan R, Van Laethem JL, Peeters M, Fuchs M, 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.PubMedCrossRef Oettle H, Richards D, Ramanathan R, Van Laethem JL, Peeters M, Fuchs M, 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.PubMedCrossRef
19.
go back to reference Senderowicz AM, Johnson JR, Sridhara R, Zimmerman P, Justice R, Pazdur R. Erlotinib/gemcitabine for first-line treatment of locally advanced or metastatic adenocarcinoma of the pancreas. Oncology (Williston Park). 2007; 21:1696–1706; discussion 1706–1699, 1712, 1715. Senderowicz AM, Johnson JR, Sridhara R, Zimmerman P, Justice R, Pazdur R. Erlotinib/gemcitabine for first-line treatment of locally advanced or metastatic adenocarcinoma of the pancreas. Oncology (Williston Park). 2007; 21:1696–1706; discussion 1706–1699, 1712, 1715.
20.
go back to reference Eckhardt SG, De Porre P, Smith D, Maurel J, Steward WP, Bouche O, et al. Patient-reported outcomes as a component of the primary endpoint in a double-blind, placebo-controlled trial in advanced pancreatic cancer. J Pain Symptom Manage. 2009;37:135–43.PubMedCentralPubMedCrossRef Eckhardt SG, De Porre P, Smith D, Maurel J, Steward WP, Bouche O, et al. Patient-reported outcomes as a component of the primary endpoint in a double-blind, placebo-controlled trial in advanced pancreatic cancer. J Pain Symptom Manage. 2009;37:135–43.PubMedCentralPubMedCrossRef
21.
go back to reference Kindler HL, Niedzwiecki D, Hollis D, Sutherland S, Schrag D, Hurwitz H, 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 (CALGB 80303). J Clin Oncol. 2010;28:3617–22.PubMedCentralPubMedCrossRef Kindler HL, Niedzwiecki D, Hollis D, Sutherland S, Schrag D, Hurwitz H, 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 (CALGB 80303). J Clin Oncol. 2010;28:3617–22.PubMedCentralPubMedCrossRef
22.
go back to reference Philip PA, Benedetti J, Corless CL, Wong R, O'Reilly EM, Flynn PJ, 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.PubMedCentralPubMedCrossRef Philip PA, Benedetti J, Corless CL, Wong R, O'Reilly EM, Flynn PJ, 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.PubMedCentralPubMedCrossRef
23.
go back to reference Goncalves A, Gilabert M, François E, Dahan L, Perrier H, Lamy R, 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.PubMedCrossRef Goncalves A, Gilabert M, François E, Dahan L, Perrier H, Lamy R, 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.PubMedCrossRef
24.
go back to reference Hu J, Zhao G, Wang HX, Tang L, Xu YC, Ma Y, et al. A meta-analysis of gemcitabine containing chemotherapy for locally advanced and metastatic pancreatic adenocarcinoma. J Hematol Oncol. 2011;4:11.PubMedCentralPubMedCrossRef Hu J, Zhao G, Wang HX, Tang L, Xu YC, Ma Y, et al. A meta-analysis of gemcitabine containing chemotherapy for locally advanced and metastatic pancreatic adenocarcinoma. J Hematol Oncol. 2011;4:11.PubMedCentralPubMedCrossRef
25.
go back to reference Breathnach OS, Freidlin B, Conley B, Green MR, Johnson DH, Gandara DR, et al. Twenty-two years of phase III trials for patients with advanced non–small-cell lung cancer: Sobering results. J Clin Oncol. 2001;19:1734–42.PubMed Breathnach OS, Freidlin B, Conley B, Green MR, Johnson DH, Gandara DR, et al. Twenty-two years of phase III trials for patients with advanced non–small-cell lung cancer: Sobering results. J Clin Oncol. 2001;19:1734–42.PubMed
26.
go back to reference Normanno N, De Luca A, Bianco C, Strizzi L, Mancino M, Maiello MR, et al. Epidermal growth factor receptor (EGFR) signaling in cancer. Gene. 2006;366:2–16.PubMedCrossRef Normanno N, De Luca A, Bianco C, Strizzi L, Mancino M, Maiello MR, et al. Epidermal growth factor receptor (EGFR) signaling in cancer. Gene. 2006;366:2–16.PubMedCrossRef
27.
go back to reference Ueda S, Ogata S, Tsuda H, Kawarabayashi N, Kimura M, Sugiura Y, et al. The correlation between cytoplasmic overexpression of epidermal growth factor receptor and tumor aggressiveness: poor prognosis in patients with pancreatic ductal adenocarcinoma. Pancreas. 2004;29:1–8.CrossRef Ueda S, Ogata S, Tsuda H, Kawarabayashi N, Kimura M, Sugiura Y, et al. The correlation between cytoplasmic overexpression of epidermal growth factor receptor and tumor aggressiveness: poor prognosis in patients with pancreatic ductal adenocarcinoma. Pancreas. 2004;29:1–8.CrossRef
28.
go back to reference Bloomston M, Bhardwaj A, Ellison EC, Frankel WL. Epidermal growth factor receptor expression in pancreatic carcinoma using tissue microarray technique. Dig Surg. 2006;23:74–9.PubMedCrossRef Bloomston M, Bhardwaj A, Ellison EC, Frankel WL. Epidermal growth factor receptor expression in pancreatic carcinoma using tissue microarray technique. Dig Surg. 2006;23:74–9.PubMedCrossRef
29.
go back to reference Scaltriti M, Baselga J. The epidermal growth factor receptor pathway: a model for targeted therapy. Clin Cancer Res. 2006;12:5268–72.PubMedCrossRef Scaltriti M, Baselga J. The epidermal growth factor receptor pathway: a model for targeted therapy. Clin Cancer Res. 2006;12:5268–72.PubMedCrossRef
30.
go back to reference Yewale C, Baradia D, Vhora I, Patil S, Misra A. Epidermal growth factor receptor targeting in cancer: a review of trends and strategies. Biomaterials. 2013;34:8690–707.PubMedCrossRef Yewale C, Baradia D, Vhora I, Patil S, Misra A. Epidermal growth factor receptor targeting in cancer: a review of trends and strategies. Biomaterials. 2013;34:8690–707.PubMedCrossRef
31.
go back to reference Bruns CJ, Shrader M, Harbison MT, Portera C, Solorzano CC, Jauch KW, et al. Effect of the vascular endothelial growth factor receptor-2 antibody DC101 plus gemcitabine on growth, metastasis and angiogenesis of human pancreatic cancer growing orthotopically in nude mice. Int J Cancer. 2002;102:101–8.PubMedCrossRef Bruns CJ, Shrader M, Harbison MT, Portera C, Solorzano CC, Jauch KW, et al. Effect of the vascular endothelial growth factor receptor-2 antibody DC101 plus gemcitabine on growth, metastasis and angiogenesis of human pancreatic cancer growing orthotopically in nude mice. Int J Cancer. 2002;102:101–8.PubMedCrossRef
Metadata
Title
Outcome of gemcitabine plus molecular targeted agent for treatment of pancreatic cancer: a meta-analysis of prospective phase III studies
Authors
Lin Chen
Ming Zhang
Shuchun Luo
Publication date
01-11-2014
Publisher
Springer Netherlands
Published in
Tumor Biology / Issue 11/2014
Print ISSN: 1010-4283
Electronic ISSN: 1423-0380
DOI
https://doi.org/10.1007/s13277-014-2451-6

Other articles of this Issue 11/2014

Tumor Biology 11/2014 Go to the issue
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine