Concomitant platinum-based chemotherapy or cetuximab with radiotherapy for locally advanced head and neck cancer: A systematic review and meta-analysis of published studies

Petrelli, Fausto; Coinu, Andrea; Riboldi, Valentina; Borgonovo, Karen; Ghilardi, Mara; Cabiddu, Mary; Lonati, Veronica; Sarti, Enrico; Barni, Sandro

doi:10.1016/j.oraloncology.2014.08.005

Cited by 115 publications

(80 citation statements)

References 27 publications

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“…It is hypothesized that the synergistic effect of gemcitabine and anti-EGFR medication results from the fact that the latter is inhibiting EGFR phosphorylation and blocking the initial survival response (EGFR activation) induced by gemcitabine and thereby promoting apoptosis. Cetuximab/ radiotherapy, because of its assumed better tolerance and compliance [72,73], often serves as an alternative for cisplatinbased CCRT in patients who might have difficulties tolerating it, albeit that a recent literature-based meta-analysis suggested inferior efficacy [74]. As the addition of cetuximab to platinumbased CCRT only adds toxicity to platinum-based CCRT without increasing efficacy [75], other cytotoxic agents with less systemic toxicity and with a different mode of action, such as gemcitabine, in combination with cetuximab and radiation, are an interesting field of research.…”

Section: Discussionmentioning

confidence: 99%

Gemcitabine-Based Chemoradiation in the Treatment of Locally Advanced Head and Neck Cancer: Systematic Review of Literature and Meta-Analysis

et al. 2015

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Background. Platinum-based concurrent chemoradiation (CCRT) improves locoregional control and overall survival of locoregionally advanced (LA) squamous cell carcinoma of the head and neck (SCCHN) when compared to radiotherapy alone, but this approach is hampered by significant toxicity. Therefore, alternative ways to enhance the radiation effects are worth investigating. Gemcitabine (29,29-difluorodeoxycytidine), in addition to its activity against a variety of solid tumors, including SCCHN, is one of the most potent radiosensitizers, and it has an overall favorable safety profile. In this paper, the clinical experience with gemcitabine-based chemoradiation in the treatment of patients with LA-SCCHN is reviewed. Methods. We conducted a review of the literature on the clinical experience with radiotherapy combined with either single-agent gemcitabine or gemcitabine/cisplatin-based polychemotherapy for the treatment of patients with LA-SCCHN. We also searched abstracts in databases of major international oncology meetings from the last 20 years. A meta-analysis was performed to calculate pooled proportions with 95% confidence intervals (CIs) for complete response rate and grade 3-4 acute mucositis rate.

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Section: Discussionmentioning

confidence: 99%

Gemcitabine-Based Chemoradiation in the Treatment of Locally Advanced Head and Neck Cancer: Systematic Review of Literature and Meta-Analysis

et al. 2015

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“…Combined modality therapy consists of surgery and radiotherapy with or without chemotherapy or molecular targeted therapy [110][111][112]. No matter what the therapeutic intervention, however, HNSCC is still associated with a high rate of recurrence [113,114].…”

Section: Carbon Ion Irradiation Counteracts Cancer Stem Cells' Migratmentioning

confidence: 99%

The impact of melatonin and carbon ion irradiation on cancer stem cells

Liu¹,

Reíter²

2017

Nucl Med Biomed Imaging

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Aim: Cancer stem cells (CSCs) exhibited an excessive migratory and invasive potential. Melatonin may inhibit multiple crucial signals associated with tumor stem cell self-renewal, viability, invasiveness, tumor growth, and therapy resistance. Carbon ion irradiation may be a promising therapeutic modality in both non-stem-like and stem-like tumor cells in contrast to photon irradiation. A comprehensive understanding of the mechanisms and molecular pathways associated with invasive properties of CSCs is essential in developing novel treatment options for cancer therapy that target CSCs. Materials and methods:A systematic review of the existing literature was conducted using the following search terms: 'melatonin', 'X-ray irradiation', 'charged particle irradiation', 'carbon ion irradiation', 'cancer stem cells', 'tumor-initiating cells' and 'cancer stem-like cells'. The search used PubMed and spanned the period from January 2000 to December 2016. Conclusion:Cancer stem cells possess the capacity of self-renewal and pluripotency, generating all cells within a tumor, and are responsible for tumor growth, therapy resistance and metastasis. Melatonin attenuated AKT activation, EZH2 S21 phosphorylation, EZH2-STAT3 interactions and altered histone modifications to reduce tumor initiation and propagation of brain tumor stem cells (BTSC). Melatonin increases the efficacy of chemotherapeutic agents, targeting both the tumor bulk and BTSCs through the regulation of the expression and function of the ABCG2/BCRP transporter by inducing the methylation of its promoter. Melatonin treatment induced cell death with ultrastructural characteristics of autophagy. Breast cancer stem cells (BCSCs) are responsive to melatonin treatment by way of reducing the viability and the invasiveness of breast cancer mammospheres as well as regulating the expression of OCT4, N-cadherin and vimentin proteins associated with epithelial mesenchymal transition in BCSCs. Carbon irradiation is effective in brain tumor stem cell (BTSC) elimination with relative biologic effectiveness (RBE) in the range of 1.87-3.44. Carbon ion irradiation may be a promising therapeutic modality because it reduces migration and invasion processes in both head and neck squamous cell carcinoma and cancer stem cells in contrast to photon irradiation. Low LET X-ray irradiation may essentially eradicate the non-stem-like tumor cells, consequently the radioresistant cancer stem-like cell population is obviously enriched. In contrast, carbon ion irradiation may eradicate both non-stemlike and stem-like tumor cells at the same time. Carbon ion irradiation is a promising tool to eradicate putative colon cancer stem-like cells. Further investigation to elucidate the mechanisms and molecular pathways involved in cancer stem cells particularly associated with melatonin and carbon ion irradiation certainly is warranted.

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“…1). Cisplatin remains a first-line chemotherapeutic agent and has been continuously used as a primary treatment modality in HNC in combination with radiotherapy in organ preservation strategies (2,3). It interferes with DNA repair mechanisms by crosslinking with the DNA purine bases, causing DNA damage and inducing apoptosis in cancer cells (4).…”

Section: Introductionmentioning

confidence: 99%

Inhibition of Glucosylceramide Synthase Sensitizes Head and Neck Cancer to Cisplatin

Roh

Kim

Park

et al. 2015

Molecular Cancer Therapeutics

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Glucosylceramide synthase (GCS) overexpression is associated with multidrug resistance in several human cancers. GCS blockade, which overcomes multidrug resistance by downregulating P-glycoprotein (P-gp), has not been tested in head and neck cancer (HNC). This study investigates whether GCS is targetable in HNC by assessing whether GCS inhibition sensitizes HNC to cisplatin. The effect of genetic or pharmacologic GCS inhibition (using GCS siRNA/shRNA or D,L-threo-PPMP, respectively) on cisplatin sensitivity was assessed in several human HNC cells and acquired cisplatin-resistant HNC cells by measuring cell viability, cell cycle, death, mRNA and protein expression, ceramide production, and in preclinical tumor xenograft mouse models. GCS and P-gp expression were significantly associated with cisplatin resistance in several HNC cell lines (P ¼ 0.007). Both were significantly increased in HN9-cisR cells, which display acquired cisplatin resistance (P < 0.001). Genetic or pharmacologic inhibition of GCS induced accumulation of increased ceramide levels. GCS inhibition increased cisplatin-induced cell death in HNC cells via P-gp downregulation and proapoptotic protein activation, which were abrogated by siPUMA transfection. Genetic and pharmacologic GCS inhibition sensitized resistant HNC cells to cisplatin in vitro and in vivo. GCS and P-gp overexpression is associated with acquired cisplatin resistance, suggesting a role for these molecules as therapeutic targets for HNC. Genetic or pharmacologic GCS blockade may have therapeutic benefit in cisplatin-resistant HNC.

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Concomitant platinum-based chemotherapy or cetuximab with radiotherapy for locally advanced head and neck cancer: A systematic review and meta-analysis of published studies

Cited by 115 publications

References 27 publications

Gemcitabine-Based Chemoradiation in the Treatment of Locally Advanced Head and Neck Cancer: Systematic Review of Literature and Meta-Analysis

Gemcitabine-Based Chemoradiation in the Treatment of Locally Advanced Head and Neck Cancer: Systematic Review of Literature and Meta-Analysis

The impact of melatonin and carbon ion irradiation on cancer stem cells

Inhibition of Glucosylceramide Synthase Sensitizes Head and Neck Cancer to Cisplatin

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