The efficiency of single agent docetaxel in patients with platinum-refractory non-small cell lung carcinoma

Uygun, Kazım; Aksu, Görkem; Çiçin, İrfan; Karagöl, Hakan; Koçak, Zafer; Fayda, Merdan; Binici, Ahmet; Uzunoglu, Fernaz

doi:10.1007/s12032-008-9055-1

Cited by 6 publications

(4 citation statements)

References 37 publications

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“…The PR rate with docetaxel was 15 % while no cilengitide-treated patient had a PR. The PR rate with docetaxel seen in this study is similar to the 13–22 % rates reported in other monotherapy studies of the taxane in advanced NSCLC [25–27]. …”

Section: Discussionsupporting

confidence: 89%

Randomized phase II study of three doses of the integrin inhibitor cilengitide versus docetaxel as second-line treatment for patients with advanced non-small-cell lung cancer

et al. 2012

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SummaryIntroduction This multicenter, open-label, phase II study was carried out to compare the efficacy and safety of cilengitide (EMD 121974), a selective inhibitor of the cell-surface integrins αVβ3 and αVβ5, with that of docetaxel in patients with advanced non-small-cell lung cancer (NSCLC). Methods Patients (n = 140) with advanced NSCLC who had failed first-line chemotherapy were randomized to cilengitide 240, 400, or 600 mg/m2 twice weekly, or docetaxel 75 mg/m2 once every 3 weeks for eight cycles. Non-progressing patients could continue cilengitide for up to 1 year. The primary endpoint was progression-free survival (PFS). No statistical tests were performed since the study was exploratory in nature and the number of patients enrolled was relatively small. Results Median PFS was 54, 63, 63, and 67 days for cilengitide 240, 400, and 600 mg/m2, and docetaxel 75 mg/m2, respectively. One-year survival rates were 13 %, 13 %, 29 %, and 27 %, respectively. The response rate (partial response only) with docetaxel was 15 %. No responses were reported in any cilengitide arm. The most frequent grade 3/4 treatment-related adverse events in the docetaxel group were leukopenia and neutropenia (experienced by 13 % of patients). Hematologic toxicity of this severity did not occur in cilengitide-treated patients. Conclusion With the highest dose of cilengitide (600 mg/m2), median PFS and 1-year survival were similar to those in patients treated with docetaxel 75 mg/m2 and there were fewer grade 3/4 treatment-related adverse events.

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Section: Discussionsupporting

confidence: 89%

Randomized phase II study of three doses of the integrin inhibitor cilengitide versus docetaxel as second-line treatment for patients with advanced non-small-cell lung cancer

et al. 2012

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“…Chemotherapy is a significant component of current first-line treatment for LAD patients. Docetaxel, a semisynthetic analogue of paclitaxel, is widely used in the treatment of LAD with genotoxic effects attributed to the induction of apoptosis and cell cycle arrest [3]. However, chemoresistance remains a major impediment to clinical application of this drug.…”

Section: Introductionmentioning

confidence: 99%

Long noncoding RNA CCAT1 acts as an oncogene and promotes chemoresistance in docetaxel-resistant lung adenocarcinoma cells

et al. 2016

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Chemoresistance remains one of the major obstacles in clinical treatment of lung adenocarcinoma (LAD). Indeed, docetaxel-resistant LAD cells present chemoresistance and epithelial-to-mesenchymal transition phenotypes. Long non-coding RNAs (lncRNAs) are known to promote tumorigenesis in many cancer types. Here, we showed that the lncRNA colon cancer-associated transcript-1 (CCAT1) was upregulated in docetaxel-resistant LAD cells. Furthermore, downregulation of CCAT1 decreased chemoresistance, inhibited proliferation, enhanced apoptosis and reversed the epithelial-to-mesenchymal transition phenotype of docetaxel-resistant LAD cells. We also found that the oncogenic function of CCAT1 in docetaxel-resistant LAD cells depended on the sponging of let-7c. In turn, the sponging of let-7c by CCAT1 released Bcl-xl (a let-7c target), thereby promoting the acquisition of chemoresistance and epithelial-to-mesenchymal transition phenotypes in docetaxel-resistant LAD cells. Our data reveal a novel pathway underlying chemoresistance and the epithelial-to-mesenchymal transition in docetaxel-resistant LAD cells.

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“…In spite of significant achievement in the treatment of LAD over the last decade, the prognosis for patients with advanced disease remains poor [2]. Docetaxel, a semi-synthetic analog of paclitaxel, was granted approval as a first-line chemotherapy regimen for NSCLC [3]. However, chemoresistance remains a major obstacle constraining the clinical application of this agent.…”

Section: Introductionmentioning

confidence: 99%

HMGB1-mediated autophagy promotes docetaxel resistance in human lung adenocarcinoma

et al. 2014

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BackgroundDocetaxel resistance remains a major obstacle in the treatment of non-small cell lung cancer (NSCLC). High-mobility group box 1 (HMGB1) has been shown to promote autophagy protection in response to antitumor therapy, but the exact molecular mechanism underlying HMGB1-mediated autophagy has not been clearly defined.MethodsLung adenocarcinoma (LAD) cells were transfected with pcDNA3.1-HMGB1 or HMGB1 shRNA, followed by docetaxel treatment. Cell viability and proliferation were tested by MTT assay and colony formation assay, respectively. Annexin V flow cytometric analysis and western blot analysis of activated caspase3 and cleaved PARP were used to evaluate apoptosis, while immunofluorescence microscopy and transmission electron microscopy were applied to assess autophagy activity. The formation of the Beclin-1-PI3K-III complex was examined by immunoprecipitation analysis. NOD/SCID mice were inoculated with docetaxel-resistant SPC-A1/DTX cells transfected with control or HMGB1 shRNA.ResultsHMGB1 translocated from the nucleus to the cytoplasm in LAD cells exposed to docetaxel and acted as a positive regulator of autophagy, which inhibited apoptosis and increased drug resistance. Suppression of HMGB1 restored the sensitivity of LAD cells to docetaxel both in vivo and in vitro. Mechanistic investigation revealed that HMGB1 promoted the formation of the Beclin-1-PI3K-III complex through activating the mitogen-activated protein kinase (MEK)-extracellular signal-regulated kinase (ERK) signaling pathway, thereby regulating autophagosome formation.ConclusionsOur results demonstrated that HMGB1-regulated autophagy is a significant contributor to docetaxel resistance in LAD cells. Suppression of HMGB1 or limiting HMGB1 cytosolic translocation diminished autophagic protection in response to docetaxel in LAD cells.

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The efficiency of single agent docetaxel in patients with platinum-refractory non-small cell lung carcinoma

Abstract: Second-line chemotherapy with single-agent docetaxel offers a small but significant survival advantage with acceptable toxicity for patients with advanced NSCLC who have platinum-refractory disease.

Cited by 6 publications

References 37 publications

Randomized phase II study of three doses of the integrin inhibitor cilengitide versus docetaxel as second-line treatment for patients with advanced non-small-cell lung cancer

Randomized phase II study of three doses of the integrin inhibitor cilengitide versus docetaxel as second-line treatment for patients with advanced non-small-cell lung cancer

Long noncoding RNA CCAT1 acts as an oncogene and promotes chemoresistance in docetaxel-resistant lung adenocarcinoma cells

HMGB1-mediated autophagy promotes docetaxel resistance in human lung adenocarcinoma

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