Concomitant radio-chemotherapy based on platin compounds in patients with locally advanced non-small cell lung cancer (NSCLC): A meta-analysis of individual data from 1764 patients

Aupérin, Anne; Péchoux, C. Le; Pignon, Jean-Pierre; Koning, Caro C.E.; Jeremić, Branislav; Clamon, Gerald H.; Einhorn, L. H.; Ball, David; Trovò, Marco; Groen, Harry J.M.; Bonner, James A.; Chevalier, Thierry Le; Arriagada, R.

doi:10.1093/annonc/mdj117

Cited by 267 publications

(133 citation statements)

References 37 publications

Supporting

Mentioning

125

Contrasting

Unclassified

Order By: Relevance

“…In lung cancer treatment, radiotherapy is often combined with concomitant application of platinum-based chemotherapeutics (24). Platinum-associated toxicities, however, can be severe and often the treatment protocol has to be adapted to deal with this.…”

Section: Discussionmentioning

confidence: 99%

Genome-wide siRNA Screen Identifies the Radiosensitizing Effect of Downregulation of MASTL and FOXM1 in NSCLC

Nagel

Walsum

Buijze

et al. 2015

Molecular Cancer Therapeutics

View full text Add to dashboard Cite

Lung cancer is the most common cancer worldwide and on top of that has a very poor prognosis, which is reflected by a 5-year survival rate of 5% to 15%. Radiotherapy is an integral part of most treatment regimens for this type of tumor, often combined with radiosensitizing cytotoxic drugs. In this study, we identified many genes that could potentially be exploited for targeted radiosensitization using a genome-wide siRNA screen in non-small cell lung cancer (NSCLC) cells. The screen identified 433 siRNAs that potentially sensitize lung cancer cells to radiation. Validation experiments showed that knockdown of expression of Forkhead box M1 (FOXM1) or microtubuleassociated serine/threonine kinase-like (MASTL) indeed causes radiosensitization in a panel of NSCLC cells. Strikingly, this effect was not observed in primary human fibroblasts, suggesting that the observed radiosensitization is specific for cancer cells. Phosphoproteomics analyses with and without irradiation showed that a number of cell-cycle-related proteins were significantly less phosphorylated after MASTL knockdown in comparison to the control, while there were no changes in the levels of phosphorylation of DNA damage response proteins. Subsequent analyses showed that MASTL knockdown cells respond differently to radiation, with a significantly shortened G 2 -M phase arrest and defects in cytokinesis, which are followed by a cell-cycle arrest. In summary, we have identified many potential therapeutic targets that could be used for radiosensitization of NSCLC cells, with MASTL being a very promising and druggable target to combine with radiotherapy.

show abstract

Section: Discussionmentioning

confidence: 99%

Genome-wide siRNA Screen Identifies the Radiosensitizing Effect of Downregulation of MASTL and FOXM1 in NSCLC

Nagel

Walsum

Buijze

et al. 2015

Molecular Cancer Therapeutics

View full text Add to dashboard Cite

show abstract

“…Patients with locally advanced NSCLC still have poor prognosis. Concurrent platin-containing CRT prolongs survival (Aupérin et al, 2006), despite the increased risk of SPC in longterm survivors. In this study, it is difficult to speculate on the association of SPC with RT because only one SPC was present in the RT field.…”

Section: Discussionmentioning

confidence: 99%

Second primary cancer in survivors following concurrent chemoradiation for locally advanced non-small-cell lung cancer

et al. 2006

View full text Add to dashboard Cite

show abstract

“…Those studies reported that healthy older adults with locally advanced NSCLC benefitted from concurrent chemoradiotherapy similar to younger patients, but experienced higher rates of hospitalization and toxicity. A previous meta-analysis reported that the benefit of concomitant chemotherapy appeared to be greater in elderly compared to that in younger patients (23).…”

Section: Discussionmentioning

confidence: 96%

Weekly administration of paclitaxel and carboplatin with concurrent thoracic radiation in previously untreated elderly patients with locally advanced non-small-cell lung cancer: A case series of 20 patients

Takeshita

Masago

Fujita

et al. 2014

Molecular and Clinical Oncology

View full text Add to dashboard Cite

Abstract. Elderly patients with stage III non-small-cell lung cancer (NSCLC) are frequently underrepresented in clinical trials that evaluate chemoradiotherapy, due to their poor functional status, coexisting illnesses and limited life expectancy. The Japan Clinical Oncology Group 0301 trial (JCOG0301) was the first study to demonstrate that thoracic radiation therapy (TRT) with daily low-dose carboplatin may improve the outcome of elderly patients with stage III NSCLC. However, the efficacy and safety profiles of chemoradiotherapy, including platinum doublets, have not been clearly determined in this patient population. We retrospectively assessed the efficacy and toxicity of weekly paclitaxel in combination with carboplatin and concurrent TRT in patients aged ≥75 years with previously untreated locally advanced NSCLC. Between February, 2004 and July, 2013, we collected the data of 20 patients treated with weekly paclitaxel and carboplatin for 6 weeks and concurrent TRT. The objective response rate was 90%, the disease control rate was 95%, the median progression-free survival was 8.63 months [95% confidence interval (CI): 5.7-16.7] and the median overall survival (OS) was 16.1 months (95% CI: 10.7-41.6). There were no grade 4 hematological or non-hematological toxicities and no reported treatment-related deaths. Therefore, platinum doublet therapy in combination with TRT did not provide a clinically significant survival benefit in our population of elderly patients with locally advanced NSCLC. However, the present study demonstrated the good feasibility and safety of this regimen. Further prospective clinical trials are required to evaluate the efficacy and safety of platinum doublet with TRT in elderly patients.

show abstract

Concomitant radio-chemotherapy based on platin compounds in patients with locally advanced non-small cell lung cancer (NSCLC): A meta-analysis of individual data from 1764 patients

Abstract: Concomitant platin-based radio-chemotherapy may improve survival of patients with locally advanced NSCLC. However, the available data are insufficient to accurately define the size of such a potential treatment benefit and the optimal schedule of chemotherapy.

Cited by 267 publications

References 37 publications

Genome-wide siRNA Screen Identifies the Radiosensitizing Effect of Downregulation of MASTL and FOXM1 in NSCLC

Genome-wide siRNA Screen Identifies the Radiosensitizing Effect of Downregulation of MASTL and FOXM1 in NSCLC

Second primary cancer in survivors following concurrent chemoradiation for locally advanced non-small-cell lung cancer

Weekly administration of paclitaxel and carboplatin with concurrent thoracic radiation in previously untreated elderly patients with locally advanced non-small-cell lung cancer: A case series of 20 patients

Contact Info

Product

Resources

About