Combination chemotherapy of gemcitabine and vinorelbine for patients in stage IIIB–IV non-small cell lung cancer: a phase II study of the West Japan Thoracic Oncology Group (WJTOG) 9908

Katakami, Nobuyuki; Sugiura, Takahiko; Nogami, T.; Yamamoto, Hidehiko; Negoro, Shunichi; Nakano, Takashi; Okamoto, Naoki; Takada, Yoshiki; Kodama, Keiji; Ariyoshi, Y

doi:10.1016/j.lungcan.2003.08.015

Cited by 15 publications

(23 citation statements)

References 27 publications

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“…NSCLC is characterized by its poor prognosis and resistance to the apoptotic activity of antineoplastic drugs both in vivo and in vitro (25,26). Although many signaling cascades have been implicated in the acquisition of chemoresistance in NSCLC (3,26,27), we conjectured that it is probable that the antiapoptotic effects of nicotine contribute to the process.…”

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confidence: 95%

“…In addition, nicotine has been also found to inhibit apoptosis induced by opioids, etoposide, cisplatin, and UV irradiation in lung cancer cells (7,10,14). The inhibitory effect of nicotine on apoptosis has been attributed to its ability to activate and phosphorylate antiapoptotic proteins like Bcl-2, induction of NF-B complexes, activation of the Akt pathway, as well as inactivation of proapoptotic proteins like Bax and Bad through phosphorylation in lung cancer cells (7,(20)(21)(22)(23)(24).NSCLC is characterized by its poor prognosis and resistance to the apoptotic activity of antineoplastic drugs both in vivo and in vitro (25,26). Although many signaling cascades have been implicated in the acquisition of chemoresistance in NSCLC (3, 26, 27), we conjectured that it is probable that the antiapoptotic effects of nicotine contribute to the process.…”

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confidence: 99%

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Nicotine inhibits apoptosis induced by chemotherapeutic drugs by up-regulating XIAP and survivin

Dasgupta

Kinkade

Joshi

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

280

263

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Non-small cell lung cancer (NSCLC) demonstrates a strong etiologic association with smoking. Although nicotine is not carcinogenic, it can induce cell proliferation and angiogenesis and suppress apoptosis induced by certain agents. Here we show that nicotine inhibits apoptosis induced by the drugs gemcitabine, cisplatin, and taxol, which are used to treat NSCLCs. This protection correlated with the induction of XIAP and survivin by nicotine in a panel of human NSCLC cell lines, and depletion of XIAP and survivin ablated the protective effects of nicotine. The antiapoptotic effects of nicotine were mediated by dihydro ␤-erythroidine-sensitive ␣3-containing nicotinic acetylcholine receptors and required the Akt pathway. Chromatin immunoprecipitation assays demonstrated that nicotine stimulation caused an increased recruitment of E2F1 and concomitant dissociation of retinoblastoma tumor suppressor protein (Rb) from survivin promoter in A549 cells. Moreover, ablation of E2F1 levels caused abrogation of the protective effects of nicotine against cisplatin-induced apoptosis in A549 cells whereas ablation of signal transducer and activator of transcription 3 levels had no effect. These studies suggest that exposure to nicotine might negatively impact the apoptotic potential of chemotherapeutic drugs and that survivin and XIAP play a key role in the antiapoptotic activity of nicotine.E2F ͉ retinoblastoma ͉ Stat 3 ͉ IAP ͉ lung cancer C igarette smoking is a major risk factor in the development of non-small cell lung cancer (NSCLC), which accounts for 80% of all lung cancers (1-3). Previous studies have implied that nicotine may be genotoxic, forming adducts with DNA, histone H1͞H3, or H1b, thereby causing mutations in vital genes leading to neoplastic transformation (4, 5). However, recent evidence has shown that nicotine can also lead to sustained activation of mitogenic pathways, promote angiogenesis, and accelerate tumor growth and atherosclerosis (6-13). Nicotine and its related carcinogens, like 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone, have been found to activate Raf-1-, EGFR-, c-Src-, Akt-, and 5-lipooxygenase-mediated growth stimulatory pathways (14-19). In addition, nicotine has been also found to inhibit apoptosis induced by opioids, etoposide, cisplatin, and UV irradiation in lung cancer cells (7,10,14). The inhibitory effect of nicotine on apoptosis has been attributed to its ability to activate and phosphorylate antiapoptotic proteins like Bcl-2, induction of NF-B complexes, activation of the Akt pathway, as well as inactivation of proapoptotic proteins like Bax and Bad through phosphorylation in lung cancer cells (7,(20)(21)(22)(23)(24).NSCLC is characterized by its poor prognosis and resistance to the apoptotic activity of antineoplastic drugs both in vivo and in vitro (25,26). Although many signaling cascades have been implicated in the acquisition of chemoresistance in NSCLC (3, 26, 27), we conjectured that it is probable that the antiapoptotic effects of nicotine contribute to the process. Here we...

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confidence: 95%

mentioning

confidence: 99%

Nicotine inhibits apoptosis induced by chemotherapeutic drugs by up-regulating XIAP and survivin

Dasgupta

Kinkade

Joshi

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

280

263

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“…Vinorelbine/gemcitabine combinations have been widely tested in NSCLC patients over the last several years [8][9][10][11]. The most common regimen combined vinorelbine 25 mg/m 2 and gemcitabine 1000 mg/m 2 both on day 1 and 8 in 3-week cycles.…”

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confidence: 99%

Randomized study of vinorelbine–gemcitabine versus vinorelbine–carboplatin in patients with advanced non-small cell lung cancer

et al. 2005

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“…We also conducted a Phase II trial of GV in patients with Stage IIIB and IV NSCLC and observed that toxicity was modest and was managed easily, and overall survival was promising (median survival, 13.9 months). 9 Several randomized Phase III trials have shown that this regimen conferred a comparable survival advantage and was less toxic than standard cisplatin-based chemotherapy. 10,11 Thus, we can state reasonably that both GC and GV are attractive alternatives to cisplatin-based chemotherapy.…”

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confidence: 99%

Randomized phase II study of carboplatin/gemcitabine versus vinorelbine/gemcitabine in patients with advanced nonsmall cell lung cancer

Yamamoto¹,

Nakagawa²,

Uejima³

et al. 2006

Cancer

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BACKGROUND. Combined gemcitabine and carboplatin (GC) and combined gemcitabine and vinorelbine (GV) are active and well tolerated chemotherapeutic regimens for patients with advanced nonsmall cell lung cancer (NSCLC). The authors conducted a randomized Phase II study of GC versus GV to compare them in terms of efficacy and toxicity. METHODS. One hundred twenty‐eight patients with Stage IIIB or IV NSCLC were randomized to receive either carboplatin at an area under the curve of 5 on Day 1 combined with gemcitabine 1000 mg/m2 on Days 1 and 8 (n = 64 patients) or vinorelbine 25 mg/m2 combined with gemcitabine 1000 mg/m2 on Days 1 and 8 (n = 64 patients) every 3 weeks. RESULTS. Response rates were 20.3% for the GC patients and 21.0% for the GV patients. In the GC arm, the median survival was 432 days, and the a 1‐year survival rate was 57.6%; in the GV arm, the median survival was 385 days, and the 1‐year survival rate was 53.3% in the GV arm. The median progression‐free survival was 165 days in the GC arm and 137 days in the GV arm. Severe hematologic toxicity (Grade 4) was significantly more frequent in the GC arm (45.3% vs. 25.8% in the GV arm; P = .022). Most notably, the incidence of Grade 3 or 4 thrombocytopenia was significantly higher in the GC arm (81.3% vs. 6.5% in the GV arm; P < .001). Conversely, severe nonhematologic toxicity (Grade 3 or 4) was more common in the GV arm (7.8% vs. 19.4% in the GC arm; P = .057). CONCLUSIONS. Although the GV and GC regimens had different toxicity profiles, there was no significant difference in survival among patients with NSCLC in the current study. Cancer 2006. © 2006 American Cancer Society.

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Combination chemotherapy of gemcitabine and vinorelbine for patients in stage IIIB–IV non-small cell lung cancer: a phase II study of the West Japan Thoracic Oncology Group (WJTOG) 9908

Cited by 15 publications

References 27 publications

Nicotine inhibits apoptosis induced by chemotherapeutic drugs by up-regulating XIAP and survivin

Nicotine inhibits apoptosis induced by chemotherapeutic drugs by up-regulating XIAP and survivin

Randomized study of vinorelbine–gemcitabine versus vinorelbine–carboplatin in patients with advanced non-small cell lung cancer

Randomized phase II study of carboplatin/gemcitabine versus vinorelbine/gemcitabine in patients with advanced nonsmall cell lung cancer

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