Phase III Study of Erlotinib in Combination With Cisplatin and Gemcitabine in Advanced Non–Small-Cell Lung Cancer: The Tarceva Lung Cancer Investigation Trial

Gatzemeier, U.; Płużańska, A; Szczęsna, Aleksandra; Kaukel, E.; Roubec, Jaromı́r; Rosa, Flavio De; Milanowski, Janusz; Karnicka-Mlodkowski, Hanna; Pešek, Miloš; Serwatowski, Piotr; Ramlau, Rodryg; Janaskova, Terezie; Vansteenkiste, Johan; Strausz, J.; Manikhas, Georgy M.; Pawel, Joachim von

doi:10.1200/jco.2005.05.1474

Cited by 801 publications

(507 citation statements)

References 49 publications

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“…In combination with chemotherapy, treatment with neither erlotinib nor gefitinib resulted in improved survival compared with chemotherapy alone (19,20). Mutations of the tyrosine kinase domain of EGFR frequently occur as a ΔE746-E750 deletion in exon 19 and as an L858R replacement in exon 21 in adenocarcinoma of NSCLC patients who exhibit dramatic tumor sensitivity to EGFR tyrosine kinase inhibitor (reviewed in ref.…”

Section: Discussionmentioning

confidence: 99%

Targeting Epidermal Growth Factor Receptor–Associated Signaling Pathways in Non–Small Cell Lung Cancer Cells: Implication in Radiation Response

Choi

Ryu

Kim

et al. 2010

Molecular Cancer Research

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Several studies have shown solid evidence for the potential value of targeting epidermal growth factor receptor (EGFR) signaling to enhance the antitumor activity of radiation. However, therapeutic resistance has emerged as an important clinical issue. Here, we investigated whether strategies for targeting EGFR-associated downstream signaling would radiosensitize a panel of non-small cell lung cancer cell lines. Inhibition of K-RAS using RNA interference attenuated downstream signaling and increased radiosensitivity of A549 and H460 cells, whereas inhibition of EGFR did not. A549 cells harboring a K-RAS mutation at codon V12 were radiosensitized by small interfering RNA (siRNA) targeting this codon. H460 cells having mutation at codon V61 was radiosensitized by siRNA targeting of this mutation. K-RAS siRNA did not radiosensitize H1299 cells possessing wild-type K-RAS. Inhibition of the phosphoinositide 3-kinase (PI3K)-AKT-mammalian target of rapamycin pathway led to significant radiosensitization of the two cell lines, whereas selective inhibition of extracellular signal-regulated kinase signaling did not. Inhibitors targeting the PI3K-AKT-mTOR pathway also abrogated G 2 arrest following irradiation and induced γH2AX foci formation. A dual inhibitor of class I PI3K and mammalian target of rapamycin effectively increased the radiosensitivity of A549 and H460 cells. Inhibition of PI3K-AKT signaling was associated with the downregulation of DNA-PKs. Although apoptosis was the primary mode of cell death when cells were pretreated with LY294002 or AKT inhibitor VIII, cells pretreated with rapamycin or PI-103 showed mixed modes of cell death, including apoptosis and autophagy. Our results suggest possible mechanisms for counteracting EGFR prosurvival signaling implicated in radioresistance and offer an alternative strategy for overcoming resistance to EGFR inhibitors used in combination with irradiation.

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Section: Discussionmentioning

confidence: 99%

Targeting Epidermal Growth Factor Receptor–Associated Signaling Pathways in Non–Small Cell Lung Cancer Cells: Implication in Radiation Response

Choi

Ryu

Kim

et al. 2010

Molecular Cancer Research

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“…In a similar study of gemcitabine-cisplatin compared with cisplatin alone, the ORRs were 30.4% and 11.1%, respectively; the risk for PD was 18% lower and the median survival duration was significantly longer in the gemcitabine arm [10]. Recent studies have investigated the benefit of adding a biological drug, namely, gefitinib (Iressa ® ; Astra-Zeneca Pharmaceuticals, Wilmington, DE), erlotinib (Tarceva ® ; OSI Pharmaceuticals, Inc., Melville, NY), or bevacizumab (Avas-tin ® ; Genentech Inc., South San Francisco, CA), to either cisplatin-gemcitabine [81][82][83] or carboplatin plus a taxane [84 -86]. Although these studies did not report PD rates, an overview of their results suggests that carboplatin-paclitaxel with or without the experimental agent usually produces numerically inferior outcomes in terms of both response and TTP.…”

Section: Discussionmentioning

confidence: 99%

Impact of Third-Generation Drugs on the Activity of First-Line Chemotherapy in Advanced Non-Small Cell Lung Cancer: A Meta-Analytical Approach

Grossi¹,

Aita²,

Defferrari³

et al. 2009

The Oncologist

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Background. The therapeutic equivalence of different third-generation agents in the first-line treatment of advanced non-small cell lung cancer (NSCLC) has long been accepted, although recent studies seem to suggest some superiority of gemcitabine-or docetaxel-containing regimens over other third-generation doublets.Objective. To assess the relative impact of different third-generation drugs on the activity of first-line chemotherapy in advanced non-small cell lung cancer by considering both response and progressive disease (PD) rates as outcome measures.Methods. Published and unpublished data were collected from randomized trials comparing a gemcitabine-, docetaxel-, vinorelbine-or paclitaxel-containing regimen with one or more gemcitabine-, docetaxel-, vinorelbine-or paclitaxel-free combinations. For

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“…Chemotherapy in general for this disease has been limited by toxicity and a lack of specificity and did not improve when combined with the epidermal growth factor receptor (EGFR) inhibitor erlotinib (2,3) or with the rexinoid bexarotene (4,5). Lung cancer chemoprevention has foundered heretofore for a variety of reasons, although very recent clinical data suggest promise in this setting (6).…”

Section: Introductionmentioning

confidence: 99%

Cotargeting Cyclin D1 Starts a New Chapter in Lung Cancer Prevention and Therapy

Kim

Lee

Wistuba

2011

Cancer Prevention Research

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Lung cancer has limited effective therapy and no effective prevention. Cytotoxic chemotherapy has not improved when combined with the epidermal growth factor receptor (EGFR) inhibitor erlotinib (standard lung cancer therapy) or with the rexinoid bexarotene. Combining erlotinib and bexarotene, however, to cotarget cyclin D1 via the retinoid X receptor and EGFR was active preclinically in KRAS-driven lung cancer cells derived from transgenic mice and in two clinical studies in lung cancer (including wild-type EGFR tumors, with or without KRAS mutations), as reported in this issue of the journal by Dragnev and colleagues (beginning on page 818). These results, along with closely related clinical results of the BATTLE program, support the promise of this cotargeting approach for lung cancer prevention and therapy and of cyclin D1 as a predictive, personalizing marker for it. Cancer Prev Res; 4(6); 779-82. Ó2011 AACR.

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Phase III Study of Erlotinib in Combination With Cisplatin and Gemcitabine in Advanced Non–Small-Cell Lung Cancer: The Tarceva Lung Cancer Investigation Trial

Abstract: Erlotinib with concurrent cisplatin and gemcitabine showed no survival benefit compared with chemotherapy alone in patients with chemotherapy-naïve advanced NSCLC.

Cited by 801 publications

References 49 publications

Targeting Epidermal Growth Factor Receptor–Associated Signaling Pathways in Non–Small Cell Lung Cancer Cells: Implication in Radiation Response

Targeting Epidermal Growth Factor Receptor–Associated Signaling Pathways in Non–Small Cell Lung Cancer Cells: Implication in Radiation Response

Impact of Third-Generation Drugs on the Activity of First-Line Chemotherapy in Advanced Non-Small Cell Lung Cancer: A Meta-Analytical Approach

Cotargeting Cyclin D1 Starts a New Chapter in Lung Cancer Prevention and Therapy

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