Literature DB >> 18379729

A phase II study evaluating bevacizumab in combination with fixed-dose rate gemcitabine and low-dose cisplatin for metastatic pancreatic cancer: is an anti-VEGF strategy still applicable?

Andrew H Ko1, Elizabeth Dito, Brian Schillinger, Alan P Venook, Zhidong Xu, Emily K Bergsland, Derrick Wong, Janet Scott, Jimmy Hwang, Margaret A Tempero.   

Abstract

BACKGROUND: The role of bevacizumab, a recombinant humanized monoclonal antibody directed against vascular endothelial growth factor, in the treatment of pancreatic cancer remains unclear. The objectives of this study were to determine safety and efficacy in chemotherapy-naive patients with metastatic pancreatic cancer receiving bevacizumab in combination with fixed-dose rate (FDR) gemcitabine and low-dose cisplatin.
METHODS: Eligible patients received gemcitabine 1,000 mg/m2 at FDR infusion (10 mg/m(2) per minute), cisplatin 20 mg/m(2), and bevacizumab 10 mg/kg, on days 1 and 15 of a 28-day cycle. Patients were monitored by computed tomography scans every two cycles and monthly serum CA19-9 measurements.
RESULTS: Of 52 patients eligible for analysis, ten (19.2%) had an unconfirmed response and 30 (57.7%) had stable disease. Of 35 patients with elevated baseline CA19-9 levels, 20 (57.1%) had > or = 50% biomarker decline during treatment. Median time to tumor progression was 6.6 months and median survival was 8.2 months (estimated 1-year survival, 36%). Grade 3/4 toxicities possibly related to bevacizumab included thromboembolic events (15.1%), hypertension (13.2%), gastrointestinal bleeding (9.4%), cardiac events (7.5%), and bowel perforation (5.7%). Plasma vascular endothelial growth factor and basic fibroblast growth factor levels and circulating tumor cell concentration did not correlate with overall survival, either at baseline or after 2 months of therapy.
CONCLUSIONS: This bevacizumab-containing study regimen is modestly effective in patients with metastatic pancreatic cancer, although occasional serious complications may occur. Given the negative results of CALGB 80303, future efforts should be focused on identifying those specific patients who are most likely to benefit from bevacizumab-based therapy.

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Year:  2008        PMID: 18379729     DOI: 10.1007/s10637-008-9127-2

Source DB:  PubMed          Journal:  Invest New Drugs        ISSN: 0167-6997            Impact factor:   3.850


  33 in total

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Authors:  Ilka Vogel; Holger Kalthoff; Doris Henne-Bruns; Bernd Kremer
Journal:  Pancreatology       Date:  2002       Impact factor: 3.996

2.  In vitro interaction between gemcitabine and other anticancer drugs using a novel three-dimensional model.

Authors:  F Kanzawa; N Saijo
Journal:  Semin Oncol       Date:  1997-04       Impact factor: 4.929

3.  Pancreatic cancer cell-derived vascular endothelial growth factor is biologically active in vitro and enhances tumorigenicity in vivo.

Authors:  J Luo; P Guo; K Matsuda; N Truong; A Lee; C Chun; S Y Cheng; M Korc
Journal:  Int J Cancer       Date:  2001-05-01       Impact factor: 7.396

4.  Phase II study of gemcitabine and cisplatin in the treatment of patients with advanced pancreatic carcinoma.

Authors:  P A Philip; M M Zalupski; V K Vaitkevicius; P Arlauskas; R Chaplen; L K Heilbrun; V Adsay; D Weaver; A F Shields
Journal:  Cancer       Date:  2001-08-01       Impact factor: 6.860

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Journal:  Clin Cancer Res       Date:  1999-03       Impact factor: 12.531

6.  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.

Authors:  Giuseppe Colucci; Francesco Giuliani; Vittorio Gebbia; Maria Biglietto; Piergiorgio Rabitti; Generoso Uomo; Silvio Cigolari; Antonio Testa; Evaristo Maiello; Massimo Lopez
Journal:  Cancer       Date:  2002-02-15       Impact factor: 6.860

7.  A phase II study of fixed-dose rate gemcitabine plus low-dose cisplatin followed by consolidative chemoradiation for locally advanced pancreatic cancer.

Authors:  Andrew H Ko; Jeanne M Quivey; Alan P Venook; Emily K Bergsland; Elizabeth Dito; Brian Schillinger; Margaret A Tempero
Journal:  Int J Radiat Oncol Biol Phys       Date:  2007-03-23       Impact factor: 7.038

8.  Weekly gemcitabine and cisplatin chemotherapy: a well-tolerated but ineffective chemotherapeutic regimen in advanced pancreatic cancer patients. A report from the Italian Group for the Study of Digestive Tract Cancer (GISCAD).

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Journal:  Clin Cancer Res       Date:  1997-08       Impact factor: 12.531

10.  A phase I clinical, plasma, and cellular pharmacology study of gemcitabine.

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Journal:  J Clin Oncol       Date:  1991-03       Impact factor: 44.544

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  27 in total

1.  Treatment-related Hypertension as a Pharmacodynamic Biomarker for the Efficacy of Bevacizumab in Advanced Pancreas Cancer: A Pooled Analysis of 4 Prospective Trials of Gemcitabine-based Therapy With Bevacizumab.

Authors:  Shubham Pant; Ludmila K Martin; Susan Geyer; Lai Wei; Katherine Van Loon; Nili Sommovilla; Mark Zalupski; Renuka Iyer; David Fogelman; Andrew H Ko; Tanios Bekaii-Saab
Journal:  Am J Clin Oncol       Date:  2016-12       Impact factor: 2.339

2.  Baseline serum albumin is a predictive biomarker for patients with advanced pancreatic cancer treated with bevacizumab: a pooled analysis of 7 prospective trials of gemcitabine-based therapy with or without bevacizumab.

Authors:  Shubham Pant; Ludmila K Martin; Susan Geyer; Lai Wei; Katherine Van Loon; Nili Sommovilla; Nilli Sommovilla; Mark Zalupski; Renuka Iyer; David Fogelman; Andrew H Ko; Tanios Bekaii-Saab
Journal:  Cancer       Date:  2014-03-13       Impact factor: 6.860

3.  Should combination chemotherapy serve as the backbone in clinical trials of advanced pancreatic cancer? A pooled analysis of phase II trials of gemcitabine-containing doublets plus bevacizumab.

Authors:  Katherine Van Loon; Anne M Espinoza; David R Fogelman; Robert A Wolff; Milind M Javle; Renuka V Iyer; Vincent J Picozzi; Ludmila Katherine Martin; Tanios Bekaii-Saab; Margaret A Tempero; Nathan R Foster; George P Kim; Andrew H Ko
Journal:  Pancreas       Date:  2014-04       Impact factor: 3.327

4.  Neutrophil granulocyte derived MMP-9 is a VEGF independent functional component of the angiogenic switch in pancreatic ductal adenocarcinoma.

Authors:  Dirk Bausch; Thomas Pausch; Tobias Krauss; Ulrich Theodor Hopt; Carlos Fernandez-del-Castillo; Andrew L Warshaw; Sarah P Thayer; Tobias Keck
Journal:  Angiogenesis       Date:  2011-03-26       Impact factor: 9.596

5.  Enhancement of nab-paclitaxel antitumor activity through addition of multitargeting antiangiogenic agents in experimental pancreatic cancer.

Authors:  Niranjan Awasthi; Changhua Zhang; Anna M Schwarz; Stefan Hinz; Margaret A Schwarz; Roderich E Schwarz
Journal:  Mol Cancer Ther       Date:  2014-03-07       Impact factor: 6.261

Review 6.  Overview of pre-clinical and clinical studies targeting angiogenesis in pancreatic ductal adenocarcinoma.

Authors:  Kelly E Craven; Jesse Gore; Murray Korc
Journal:  Cancer Lett       Date:  2015-12-23       Impact factor: 8.679

7.  Nintedanib, a triple angiokinase inhibitor, enhances cytotoxic therapy response in pancreatic cancer.

Authors:  Niranjan Awasthi; Stefan Hinz; Rolf A Brekken; Margaret A Schwarz; Roderich E Schwarz
Journal:  Cancer Lett       Date:  2014-12-16       Impact factor: 8.679

Review 8.  Systemic therapies for pancreatic cancer--the role of pharmacogenetics.

Authors:  Ross A Soo; Wei-Peng Yong; Federico Innocenti
Journal:  Curr Drug Targets       Date:  2012-06       Impact factor: 3.465

9.  EMMPRIN expression is required for response to bevacizumab therapy in HNSCC xenografts.

Authors:  J Robert Newman; Emily E Helman; Seena Safavy; Wenyue Zhang; Eben L Rosenthal
Journal:  Cancer Lett       Date:  2008-11-05       Impact factor: 8.679

Review 10.  Biomarkers of angiogenesis and their role in the development of VEGF inhibitors.

Authors:  N Murukesh; C Dive; G C Jayson
Journal:  Br J Cancer       Date:  2009-12-15       Impact factor: 7.640

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