Role of gemcitabine-based combination therapy in the management of advanced pancreatic cancer: A meta-analysis of randomised trials

Ciliberto, Domenico; Botta, Cirino; Correale, Pierpaolo; Rossi, Marco; Caraglia, Michele; Tassone, Pierfrancesco; Tagliaferri, Pierosandro

doi:10.1016/j.ejca.2012.08.019

Cited by 111 publications

(72 citation statements)

References 72 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Two meta-analyses of randomized controlled trials (RCTs) found that gemcitabine combinations give a marginal benefit in OS over gemcitabine monotherapy in the advanced setting, with a significant increase in toxicity. 49,50 Combinations recommended in the advanced setting are discussed in the following sections. Of note, results from several studies have indicated that the benefit of gemcitabine combination chemotherapy is predominantly seen in patients with good PS.…”

Section: Gemcitabine Combinationsmentioning

confidence: 99%

Pancreatic Adenocarcinoma, Version 2.2017, NCCN Clinical Practice Guidelines in Oncology

Tempero

Malafa

Al-Hawary

et al. 2017

J Natl Compr Canc Netw

938

897

View full text Add to dashboard Cite

OverviewPancreatic cancer is one of the most common causes of cancer-related death among men and women in the United States. Abstract Ductal adenocarcinoma and its variants account for most pancreatic malignancies. High-quality multiphase imaging can help to preoperatively distinguish between patients eligible for resection with curative intent and those with unresectable disease. Systemic therapy is used in the neoadjuvant or adjuvant pancreatic cancer setting, as well as in the management of locally advanced unresectable and metastatic disease. Clinical trials are critical for making progress in treatment of pancreatic cancer. The NCCN Guidelines for Pancreatic Adenocarcinoma focus on diagnosis and treatment with systemic therapy, radiation therapy, and surgical resection. J Natl Compr Canc Netw 2017;15(8):1028-1061 doi: 10.6004/jnccn.2017 NCCN Categories of Evidence and Consensus Please NoteThe These guidelines are also available on the Internet. For the latest update, visit NCCN.org.

show abstract

Section: Gemcitabine Combinationsmentioning

confidence: 99%

Pancreatic Adenocarcinoma, Version 2.2017, NCCN Clinical Practice Guidelines in Oncology

Tempero

Malafa

Al-Hawary

et al. 2017

J Natl Compr Canc Netw

938

897

View full text Add to dashboard Cite

show abstract

“…The evidence for platinum therapy in PDAC is ever increasing in the neoadjuvant, adjuvant and palliative settings (42)(43)(44)(45)(46)(47). Exceptional responders to platinum therapy are well documented, yet biomarkers of response require testing in prospective clinical trials (9,39).…”

Section: Targeting Ddr Deficiencymentioning

confidence: 99%

Pancreatic Cancer Genomes: Implications for Clinical Management and Therapeutic Development

Dreyer

Chang

Bailey

et al. 2017

Clinical Cancer Research

146

114

View full text Add to dashboard Cite

Pancreatic cancer has become the 3 rd leading cause of cancer death, with little improvement in outcomes despite decades of research. Surgery remains the only chance of cure, yet, only 20% will be alive at 5 years after pancreatic resection. Few chemotherapeutics provide any improvement in outcome, and even then, for approved therapies, the survival benefits are marginal. Genomic sequencing studies of pancreatic cancer have revealed a small set of consistent mutations found in most pancreatic cancers, and beyond that a low prevalence for targetable mutations. This may explain the failure of conventional clinical trial designs to show any meaningful survival benefit, except in small and undefined patient sub-groups. With the development of next generation sequencing technology, genomic sequencing and analysis can be performed in a clinically meaningful turnaround time. This can identify therapeutic targets in individual patients and personalize treatment selection.Incorporating pre-clinical discovery and molecularly guided therapy into clinical trial design has the potential to significantly improve outcomes in this lethal malignancy. In this review, we discuss the findings of recent large scale genomic sequencing projects in pancreatic cancer and the potential relevance of these data to therapeutic development.3

show abstract

“…However, the median overall survival of gemcitabine treated patients with advanced pancreatic cancer is still only 5-6 months (53). To improve the prognosis of patients, low dose gemcitabine therapy combined with radiotherapy or other chemotherapeutic agents has been used, but with few exceptions, no improvement in the overall survival rates of patients with advanced pancreatic cancer has been reported (54,55). Some EGFR inhibitors (e.g., erlotinib) are approved for lung cancer, however, available data are inconclusive for treatment of pancreatic cancer patients with EGFR-targeted therapies (56).…”

Section: Discussionmentioning

confidence: 99%

Cantharidin and norcantharidin impair stemness of pancreatic cancer cells by repressing the β-catenin pathway and strengthen the cytotoxicity of gemcitabine and erlotinib

Wang

Shen

et al. 2015

International Journal of Oncology

View full text Add to dashboard Cite

Abstract. Increasing evidence suggests that tumors are composed of a heterogeneous cell population with a small subset of cancer stem cells (CSCs) that sustain tumor formation and growth, and are hypothesized to account for therapeutic resistance. Based on the expression of the surface markers CD44, CD24, and EPCAM, putative CSCs have also been identified in pancreatic cancers. It has been well established that aberrant activation of β-catenin signaling pathway may contribute to the maintenance of CSCs. Cantharidin is an active constituent of mylabris, a traditional Chinese medicine. In our previous studies, we demonstrated that cantharidin treatment induced phosphorylation of β-catenin, leading to repression on β-catenin pathway. Therefore, in the present study, we investigated whether cantharidin and its derivant, norcantharidin, could repress the stemness of pancreatic cancer cells through repression on β-catenin pathway. By using microarray and flow cytometry, we found that treatment with cantharidin and norcantharidin repressed the expression of CD44, CD24, and EPCAM at both mRNA and protein levels, leading to decreased CD44 + /CD24 + /EPCAM + proportion, the putative pancreatic CSC subset. Pretreatment with the β-catenin pathway inhibitor FH535, attenuated the cantharidin-and norcantharidin-inducrd repression on CD44, CD24, and EPCAM, suggesting cantharidin and its derivant repressed stemness of pancreatic cancer cells in β-catenin pathway-dependent manner. Furthermore, cantharidin and norcantharidin strengthened the cytotoxicity of gemcitabine and erlotinib, two well established pharmacotherapeutics against pancreatic cancers, indicating cantharidin and norcantharidin could be promising candidates for reversing drug resistance in pancreatic cancers. In conclusion, we presently propose that cantharidin and norcantharidin hold their promise in pancreatic cancer therapy through repression on stemness and strengthening the cytotoxicity of the present therapeutics.

show abstract

Role of gemcitabine-based combination therapy in the management of advanced pancreatic cancer: A meta-analysis of randomised trials

Cited by 111 publications

References 72 publications

Pancreatic Adenocarcinoma, Version 2.2017, NCCN Clinical Practice Guidelines in Oncology

Pancreatic Adenocarcinoma, Version 2.2017, NCCN Clinical Practice Guidelines in Oncology

Pancreatic Cancer Genomes: Implications for Clinical Management and Therapeutic Development

Cantharidin and norcantharidin impair stemness of pancreatic cancer cells by repressing the β-catenin pathway and strengthen the cytotoxicity of gemcitabine and erlotinib

Contact Info

Product

Resources

About