Multicentre randomised phase III study comparing the same dose and schedule of cisplatin plus the same schedule of vinorelbine or gemcitabine in advanced non-small cell lung cancer

Martoni, Andrea; Marino, Antonella; Sperandi, Francesca; Giaquinta, S.; Fabio, Francesca Di; Melotti, Barbara; Guaraldi, M.; Palomba, Giuseppe; Preti, P.; Petralia, Antonino; Artioli, Fabrizio; Picece, Vincenzo; Farris, A.; Mantovani, LG

doi:10.1016/j.ejca.2004.08.029

Cited by 66 publications

(78 citation statements)

References 28 publications

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“…For vinorelbine/platinum combinations, recent phase III studies have yielded median survival data ranging from 6.5 to 11 months (Wozniak et al, 1998;Kelly et al, 2001;Scagliotti et al, 2002;Fossella et al, 2003;Gebbia et al, 2003;Georgoulias et al, 2005;Martoni et al, 2005;Tan et al, 2005;Plessen et al, 2006). In the gemcitabine/platinum metaanalysis (Le Chevalier et al, 2005), median survival in the gemcitabine group was 9 months, reflecting the mean value for a number of studies (Le Chevalier et al, 1994;Cardenal et al, 1999;Sandler et al, 2000;Scagliotti et al, 2002;Schiller et al, 2002;Alberola et al, 2003;Gebbia et al, 2003;Smit et al, 2003;Zatloukal et al, 2003;Martoni et al, 2005;Rudd et al, 2005;Sederholm et al, 2005). Our shorter median survival is possibly explained by the high proportion of patients with PS 2 (28%), which is the most powerful predictor of survival in NSCLC patients (Stanley, 1980).…”

Section: Discussionmentioning

confidence: 99%

Vinorelbine/carboplatin vs gemcitabine/carboplatin in advanced NSCLC shows similar efficacy, but different impact of toxicity

et al. 2007

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This randomised phase III study in advanced non-small cell lung cancer (NSCLC) patients was conducted to compare vinorelbine/ carboplatin (VC) and gemcitabine/carboplatin (GC) regarding efficacy, health-related quality of life (HRQOL) and toxicity. Chemonaive patients with NSCLC stage IIIB/IV and WHO performance status 0 -2 were eligible. No upper age limit was defined. Patients received vinorelbine 25 mg m À2 or gemcitabine 1000 mg m À2 on days 1 and 8 and carboplatin AUC4 on day 1 and three courses with 3-week cycles. HRQOL questionnaires were completed at baseline, before chemotherapy and every 8 weeks until 49 weeks. During 14 months, 432 patients were included (VC, n ¼ 218; GC, n ¼ 214). Median survival was 7.3 vs 6.4 months, 1-year survival 28 vs 30% and 2-year survival 7 vs 7% in the VC and GC arm, respectively (P ¼ 0.89). HRQOL, represented by global QOL, nausea/vomiting, dyspnoea and pain, showed no significant differences. More grade 3 -4 anaemia (Po0.01), thrombocytopenia (Po0.01) and transfusions of blood (Po0.01) or platelets (Po0.01) were observed in the GC arm. There was more grade 3 -4 leucopoenia (Po0.01) in the VC arm, but the rate of neutropenic infections was the same (P ¼ 0.87). In conclusion, overall survival and HRQOL are similar, while grade 3 -4 toxicity requiring interventions are less frequent when VC is compared to GC in advanced NSCLC.

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Section: Discussionmentioning

confidence: 99%

Vinorelbine/carboplatin vs gemcitabine/carboplatin in advanced NSCLC shows similar efficacy, but different impact of toxicity

et al. 2007

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“…The majority of patients with NSCLC present with locally advanced inoperable or metastatic diseases (Silvestri and Spiro, 2006), and the use of cytotoxic chemotherapies can improve the median overall survival (Schiller et al, 2002). Gemcitabine, a pyrimidine analog, has been clinically used for patients with NSCLC (Martoni et al, 2005). The antiproliferative action of gemcitabine in pancreatic cancer cells results from the induction of apoptosis mediated by the activation of p38 mitogen-activated protein kinase (Koizumi et al, 2005).…”

Section: Introductionmentioning

confidence: 99%

Down-Regulation of Rad51 Expression Overcomes Drug Resistance to Gemcitabine in Human Non–Small-Cell Lung Cancer Cells

Tsai

Kuo²,

Chiu³

et al. 2010

J Pharmacol Exp Ther

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Gemcitabine (2Ј,2Ј-difluorodeoxycytidine), a deoxycytidine analog, and erlotinib, an epidermal growth factor receptor-tyrosine kinase inhibitor, are used clinically to treat patients with nonsmall-cell lung cancer (NSCLC). However, the molecular mechanisms for the drug resistance of gemcitabine in NSCLC cells are poorly understood. In this study, we used constructs containing human Rad51 cDNA or specific Rad51 small interfering RNA (siRNA) to examine the role of Rad51 in chemoresistance of gemcitabine in three different human NSCLC cell lines. Exposure of human NSCLC cell lines to gemcitabine increased the phosphorylation levels of mitogen-activated protein kinase kinase (MKK) 1/2-extracellular signal-regulated kinase (ERK) 1/2 and AKT in a time-and dose-dependent manner, which was accompanied by an induction of Rad51 mRNA and protein expression. Gemcitabine increased the expression of Rad51 by increasing its mRNA and protein stability. Blockage of ERK1/2 or AKT activation by 1,4-diamino-2,3-dicyano-1,4-bis(methylthio)butadiene (U0126; MKK1/2 inhibitor) or 2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one (LY294002; phosphatidyl inositol 3-kinase inhibitor), respectively, decreased the gemcitabine-induced Rad51 expression. Gemcitabine-induced cytotoxicity was significantly increased using siRNA depletion of Rad51 or blockage of ERK1/2 and AKT activation. Erlotinib enhanced the gemcitabine-induced cytotoxicity via the inactivation of ERK1/2 and AKT and the down-regulation of Rad51. Enforced expression of constitutively active MKK1/2 or AKT recovered cell viability and Rad51 protein levels that were decreased by the combination of erlotinib and gemcitabine. Suppression of Rad51 expression or the inactivation of ERK1/2 or AKT signaling may be considered potential therapeutic modalities for gemcitabine-resistant lung cancer.

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“…The cytotoxic chemotherapies can improve the median overall survival of NSCLC patients [3]. Gemcitabine (2′, 2′-difluorodeoxycytidine, dFdC) has been clinically utilized for NSCLC patients [4]. It′s cytotoxic effect requires intracellular transport and activation [5,6].…”

Section: Introductionmentioning

confidence: 99%

Down-Regulation of MutS Homolog 2 (MSH2) Expression by Curcumin Enhances Cytotoxicity Induced by Gemcitabine in Human Lung Adenocarcinoma Cells

Ko¹,

Peng²,

Wu³

et al. 2017

Epidemiology

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Multicentre randomised phase III study comparing the same dose and schedule of cisplatin plus the same schedule of vinorelbine or gemcitabine in advanced non-small cell lung cancer

Cited by 66 publications

References 28 publications

Vinorelbine/carboplatin vs gemcitabine/carboplatin in advanced NSCLC shows similar efficacy, but different impact of toxicity

Vinorelbine/carboplatin vs gemcitabine/carboplatin in advanced NSCLC shows similar efficacy, but different impact of toxicity

Down-Regulation of Rad51 Expression Overcomes Drug Resistance to Gemcitabine in Human Non–Small-Cell Lung Cancer Cells

Down-Regulation of MutS Homolog 2 (MSH2) Expression by Curcumin Enhances Cytotoxicity Induced by Gemcitabine in Human Lung Adenocarcinoma Cells

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