Oral vinorelbine in the treatment of non-small-cell lung cancer

Barletta, Giulia; Genova, Carlo; Rijavec, Erika; Burrafato, Giovanni; Biello, Federica; Sini, Claudio; Bello, Maria Giovanna Dal; Coco, Simona; Truini, Anna; Vanni, Irene; Alama, Angela; Beltramini, Sabrina; Grassi, M.; Boccardo, Francesco; Grossi, Francesco

doi:10.1517/14656566.2014.934224

Cited by 24 publications

(22 citation statements)

References 48 publications

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“…Those patients should therefore be evaluated in terms of the risk-benefit ratio of treatment. Many prefer oral rather than intravenous treatment 5,13,14 . Chemotherapy with a single agent is an acceptable option for a significant percentage of patients with stage iii or iv nsclc 15 .…”

Section: Discussionmentioning

confidence: 99%

Efficacy of Metronomic Vinorelbine in Elderly Patients with Advanced Non-Small-Cell Lung Cancer and Poor Performance Status

et al. 2017

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Section: Discussionmentioning

confidence: 99%

Efficacy of Metronomic Vinorelbine in Elderly Patients with Advanced Non-Small-Cell Lung Cancer and Poor Performance Status

et al. 2017

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“…Subsequently, a phase II clinical study was conducted to test the sequential usage of GEF with VNB for the treatment of advanced NSCLC patients. In that study, 48 Asian patients were randomized to receive GEF in monotherapy or sequential association of VNB (15 mg m − ) every 2 weeks followed by GEF taken from day 2 to day 14 of each cycle; the addition of low‐dose VNB to GEF was well tolerated and added survival benefit to the patients with adenocarcinoma of the lung who had failed at least two lines of treatment.…”

Section: Discussionmentioning

confidence: 99%

“…The most common treatment regimen involves using a platinum derivate in combination with either a third‐generation drug ( e.g ., vinorelbine, gemcitabine, paclitaxel, docetaxel, pemetrexed) or a monoclonal antibody ( e.g ., bevacizumab) . Vinorelbine (VNB) arrests proliferating cells in the G2/M phase of the cell cycle by inhibiting the polymerization of tubulin and inducing the de‐polymerization of microtubules .…”

mentioning

confidence: 99%

“…The most common treatment regimen involves using a platinum derivate in combination with either a thirdgeneration drug (e.g., vinorelbine, gemcitabine, paclitaxel, docetaxel, pemetrexed) or a monoclonal antibody (e.g., bevacizumab). 2,3 Vinorelbine (VNB) arrests proliferating cells in the G2/M phase of the cell cycle by inhibiting the polymerization of tubulin and inducing the de-polymerization of microtubules. 2 The administration of cisplatin or carboplatin in addition to intravenous VNB is the current standard in the adjuvant setting, but the effectiveness of oral VNB has only been confirmed in small retrospective analyses.…”

mentioning

confidence: 99%

“…2,3 Vinorelbine (VNB) arrests proliferating cells in the G2/M phase of the cell cycle by inhibiting the polymerization of tubulin and inducing the de-polymerization of microtubules. 2 The administration of cisplatin or carboplatin in addition to intravenous VNB is the current standard in the adjuvant setting, but the effectiveness of oral VNB has only been confirmed in small retrospective analyses. 4,5 Oral VNB is an appealing agent for combination with platinum derivatives in advanced NSCLC patients because its safety profile and route of administration allow it to be used as a monotherapy in elderly and unfit patients as well as in "metronomic chemotherapy."…”

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confidence: 99%

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Sequential use of vinorelbine followed by gefitinib enhances the antitumor effect in NSCLC cell lines poorly responsive to reversible EGFR tyrosine kinase inhibitors

Bello

Alama

Barletta

et al. 2015

Intl Journal of Cancer

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Preclinical studies have suggested that combining cytotoxic agents with epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) to treat EGFR-mutated tumors may increase their inhibitory effect depending on the order of drug administration. The antitumor efficacy of different treatment sequences using vinorelbine (VNB) and gefitinib (GEF) was investigated both in vitro and in vivo in non-small cell lung cancer (NSCLC) cell lines with the rationale of potentially translating these findings into the clinical setting. The EGFR-wild-type A549 and the EGFR-mutated (exon 21 L858R/exon 20 T790M) H1975 cell lines were treated as follows: GEF followed by VNB, VNB followed by GEF and the two drugs applied individually or concurrently. Results in vitro demonstrated that the sequence of VNB followed by GEF was significantly more active than singleagent treatments. The expression of activated EGFR and its downstream pathway genes indicated that the increased cytotoxic effect of the VNB and GEF treatment sequence was accompanied by inhibition of EGFR, AKT and ERK1/2. Moreover, the increased inhibition of tumor growth after treatment with VNB followed by GEF was also confirmed in CD1-nude mice that were xenotransplanted with H1975 cells (p < 0.0001). This effect was paralleled by a corresponding decrease in cancer glucose consumption, as assessed by micro-positron emission tomography scans (p < 0.05). These preclinical findings in NSCLC cell lines, which are poorly responsive to EGFR-TKIs, demonstrated that the sequential treatment of VNB followed by GEF induced a significant antitumor effect, which supports the translation of this treatment schedule into a clinical setting.Lung cancer is the leading cause of cancer-related mortality and causes more than a million deaths per year. Non-small cell lung cancer (NSCLC) accounts for >85% of all lung cancers, and the majority of patients are already at an advanced stage of disease by the time of diagnosis. 1 The prognosis of patients affected by advanced disease is very poor, with a 5-year survival rate of 20%. Platinum-based chemotherapy is the standard of care for patients who do not exhibit either activating mutations of EGFR or the translocation of ALK. The most common treatment regimen involves using a platinum derivate in combination with either a thirdgeneration drug (e.g., vinorelbine, gemcitabine, paclitaxel, docetaxel, pemetrexed) or a monoclonal antibody (e.g., bevacizumab). 2,3 Vinorelbine (VNB) arrests proliferating cells in the G2/M phase of the cell cycle by inhibiting the polymerization of tubulin and inducing the de-polymerization of

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Preclinical studies on the antitumor and non‐toxic effect of combining pirfenidone with vinorelbine and carboplatin in non‐small cell lung cancer

Branco,

Rodrigues,

Oliveira

et al. 2024

Intl Journal of Cancer

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Non‐small cell lung cancer (NSCLC) shows limited therapeutic response to vinorelbine and carboplatin. Combining these drugs with an antifibrotic drug may enhance their antitumor effect. Pirfenidone is an antifibrotic drug whose antitumor activity has been described in different types of cancer. This work aimed to perform preclinical studies on the combination of pirfenidone with vinorelbine, or with vinorelbine plus carboplatin, in NSCLC. Our data revealed that pirfenidone sensitized three NSCLC cell lines to vinorelbine by reducing cell growth, viability and proliferation, inducing alterations in the cell cycle profile, and increasing cell death (%). Importantly, pirfenidone increased the sensitivity of the three NSCLC cell lines to the combined treatment of vinorelbine plus carboplatin. This combined drug treatment (triplet) did not induce cytotoxicity against non‐tumorigenic cells. Notably, the triplet drug combination significantly reduced the growth and proliferation of A‐549 xenografts in nude mice, as also reduced vimentin and collagen expression. Most interestingly, the triplet treatment exhibited a safer toxicological profile than the doublet (vinorelbine plus carboplatin) currently applied in the clinical practice. Altogether, these preclinical data support the possibility of repurposing pirfenidone in combination with vinorelbine or with vinorelbine plus carboplatin for NSCLC perioperative treatment, improving therapeutic efficacy while reducing toxicity.

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Oral vinorelbine in the treatment of non-small-cell lung cancer

Cited by 24 publications

References 48 publications

Efficacy of Metronomic Vinorelbine in Elderly Patients with Advanced Non-Small-Cell Lung Cancer and Poor Performance Status

Efficacy of Metronomic Vinorelbine in Elderly Patients with Advanced Non-Small-Cell Lung Cancer and Poor Performance Status

Sequential use of vinorelbine followed by gefitinib enhances the antitumor effect in NSCLC cell lines poorly responsive to reversible EGFR tyrosine kinase inhibitors

Preclinical studies on the antitumor and non‐toxic effect of combining pirfenidone with vinorelbine and carboplatin in non‐small cell lung cancer

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