Gemcitabine plus vinorelbine for the treatment of advanced non-small cell lung cancer

Barón, Francisco; Cueva, J; Graña, Begoña; Curiel, Teresa; León, L.; Vázquez, Francisca; Candamio, Sonia; López, Rafael

doi:10.1016/s0959-8049(01)00129-0

Cited by 9 publications

(5 citation statements)

References 18 publications

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Section: Abstract: Apoptosis; Vesicular Stomatitis Virus; Gemcitabinmentioning

confidence: 99%

“…10 -12 When combined with cisplatin and/or paclitaxel or vinorelbine, gemcitabine therapy shows an objective response rates in 28 -54% and the median survival durations ranged from 38 to 61.5 weeks. [13][14][15][16][17][18] However, the treatment of advanced lung cancer still remains a challenge to medical oncologists.Because of differences in mechanisms of action and toxicity profiles, the combination of the above 2 agents may have clinical potential. The present study was designed to determine whether gemcitabine potentiates the antitumor activity of VSV in vitro using both A549 (human lung adenocarcinoma) and LLC (murine Lewis lung carcinoma) cell lines and in vivo using A549 lung cancer xenografts and the murine syngeneic Lewis lung cancer, and if so, to examine the possible mechanism in the phenomenon, as well as to provide some potential implications for the treatment of human lung cancer.…”

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confidence: 99%

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Induction of apoptosis and tumor regression by vesicular stomatitis virus in the presence of gemcitabine in lung cancer

Wei

Wang

et al. 2004

Intl Journal of Cancer

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Key words: apoptosis; vesicular stomatitis virus; gemcitabine; lung cancer; chemotherapyLung cancer accounts for about 1.5 million cases worldwide and is the leading cause of cancer-related death in both males and females. Non small cell lung cancer (NSCLC) comprises approximately 75-80% of all lung cancers. Despite aggressive approaches made in the therapy of lung cancer in the past decades, the prognosis of NSCLC remains poor, with 5-year survival rates of 5-14%, even if treated with surgery, radiotherapy and/or chemotherapy. 1-3 Efforts are therefore continuing to develop new and less toxic therapeutic approaches for the treatment of lung cancer.Vesicular stomatitis virus (VSV) is an enveloped, negativesense RNA virus and prototypic member of the family rhabdoviridae. 4 -6 It has been shown to replicate rapidly in vitro and kill selectively a variety of tumor cell lines. An essential, dose-limiting site of chemotherapy is the bone marrow while VSV can selectively kill leukemia cells when cocultured with normal bone marrow cells. 4 Furthermore, VSV exhibits the antitumor activity in both human tumor xenografts in nude mice and syngeneic tumors in the immunocompetent mice. 4,5 Gemcitabine (2Ј,2Ј-diflurodeoxycytidine) is a new deoxycytidine analogue that inhibits DNA synthesis. After cellular uptake, gemcitabine is phosphorylated to its active metabolites, which competitively inhibits DNA chain elongation, leading to DNA fragmentation and cell death. Gemcitabine has shown cytotoxic activity against a wide range of cancer cell lines in vitro and a number of murine and human tumors in vivo. [7][8][9] Gemcitabine monotherapy produced objective response in 20 -25% of patients with advanced NSCLC and has similar efficacy to cisplatin plus etoposide. 10 -12 When combined with cisplatin and/or paclitaxel or vinorelbine, gemcitabine therapy shows an objective response rates in 28 -54% and the median survival durations ranged from 38 to 61.5 weeks. [13][14][15][16][17][18] However, the treatment of advanced lung cancer still remains a challenge to medical oncologists.Because of differences in mechanisms of action and toxicity profiles, the combination of the above 2 agents may have clinical potential. The present study was designed to determine whether gemcitabine potentiates the antitumor activity of VSV in vitro using both A549 (human lung adenocarcinoma) and LLC (murine Lewis lung carcinoma) cell lines and in vivo using A549 lung cancer xenografts and the murine syngeneic Lewis lung cancer, and if so, to examine the possible mechanism in the phenomenon, as well as to provide some potential implications for the treatment of human lung cancer. MATERIAL AND METHODS Cells lines and agentsLLC cells and A549 cells were purchased from American Type Culture Collection (Rockville, MD). They were maintained in monolayer cultures in DMEM and RPMI-1640, respectively, supplemented with 10% heat-inactivated fetal bovine serum (FBS), at 37°C in a humidified atmosphere containing 5% CO 2 . Human umbilical vein endothelial cells (HU...

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Section: Abstract: Apoptosis; Vesicular Stomatitis Virus; Gemcitabinmentioning

confidence: 99%

mentioning

confidence: 99%

Induction of apoptosis and tumor regression by vesicular stomatitis virus in the presence of gemcitabine in lung cancer

Wei

Wang

et al. 2004

Intl Journal of Cancer

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“…These agents are well tolerated, even for the elderly and for patients with borderline performance status or renal function. Phase II studies using gemcitabine/vinorelbine combinations have yielded response rates of 25-40% [11][12][13][14][15] in patients with advanced NSCLC. Good tolerability and efficacy have been demonstrated with gemcitabine 1000 mg/m 2 and vinorelbine 25 mg/m 2 , both given on D 1,8 every 3 weeks [14].…”

Section: Introduction and Purposementioning

confidence: 99%

A phase II trial of induction gemcitabine and vinorelbine followed by concurrent vinorelbine and radiotherapy in locally advanced non-small cell lung cancer

et al. 2010

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“…Clinically, a gemcitabine and vinorelbine combination is tolerable in patients with NSCLC and the treatment results are constructive [23]. But in our study, in spite of the drugs having different targets in the cell, this combination showed similar results to the gemcitabine alone group.…”

Section: Discussionmentioning

confidence: 44%

Selective COX-2 Inhibitor (Rofecoxib) Inhibits Vinorelbine Cytotoxicity in C6 Glioma Cells In Vitro

Tuna¹,

Altinöz²,

Karasu³

et al. 2009

TOPATJ

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We examined the effects of gemcitabine, a novel nucleotide analogue, and vinorelbine, a semi-synthetic vinca alcaloid, in C6 glioma cell culture. We simultaneously monitored the modulation of its activity in combination with the telomerase inhibitory agent dimetilsülfoxid and with a specific cyclooxygenase-2 inhibitory agent Rofecoxib. The effects of the gemcitabine/ vinorelbine combination were observed over a 96 hour period. Plating, S-phase (bromodeoxyuridinelabelling index) and ultrastructure were selected as the evaluation parameters of drug interactions. Gemcitabine (10 g/ml) was found to possess significant blocking activity of C6 glioma plating and cells' S-phase. Vinorelbine (10 g/ml) also demonstrated significant inhibitory activity. Vinorelbine reduced BrdU-LI but was not as effective as gemcitabine. Rofecoxib (10 g/ml) showed no synergism on cell inhibition either with gemcitabine or vinorelbine and protected against the S-phase depleting activity of vinorelbine. Dimetilsülfoxid (20 g/ml) reduced the effect of vinorelbine in spheroid culture. But at the final 96 th hour tie point dimetilsülfoxid reduced the increasing cell numbers which were previously seen in the gemcitabine group. In conclusion, both gemcitabine and vinorelbine effectively reduced both the monolayer and spheroid growth of C6 glioma cells. At the single cell level, only dimetilsülfoxid could sensitise for gemcitabine but not vinorelbine. Despite reducing spheroid growth, treatment using cyclooxygenase-2 inhibitors with microtubule inhibitors should be avoided.

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Gemcitabine plus vinorelbine for the treatment of advanced non-small cell lung cancer

Cited by 9 publications

References 18 publications

Induction of apoptosis and tumor regression by vesicular stomatitis virus in the presence of gemcitabine in lung cancer

Induction of apoptosis and tumor regression by vesicular stomatitis virus in the presence of gemcitabine in lung cancer

A phase II trial of induction gemcitabine and vinorelbine followed by concurrent vinorelbine and radiotherapy in locally advanced non-small cell lung cancer

Selective COX-2 Inhibitor (Rofecoxib) Inhibits Vinorelbine Cytotoxicity in C6 Glioma Cells In Vitro

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