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vinflunine

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Description

vinflunine: inhibits tubulin assembly; structure in first source [Medical Subject Headings (MeSH), National Library of Medicine, extracted Dec-2023]

vinflunine : An organic heteropentacyclic compound and an organic heterotetracyclic compound that is vinorelbine in which the tetrahydropyridine moiety of the heterotetracyclic part of the molecule has been redced to the corresponding piperidine, and in which the ethyl group attached to this ring has been replaced by a 1,1-difluoroethyl group. [Chemical Entities of Biological Interest (ChEBI), Hastings J, Owen G, Dekker A, Ennis M, Kale N, Muthukrishnan V, Turner S, Swainston N, Mendes P, Steinbeck C. (2016). ChEBI in 2016: Improved services and an expanding collection of metabolites. Nucleic Acids Res]

Cross-References

ID SourceID
PubMed CID10629256
CHEMBL ID2110725
CHEBI ID90241
MeSH IDM0288082

Synonyms (30)

Synonym
vinflunine
l-0070
4'-deoxy-20',20'-difluoro-8'-norvincaleukoblastine
4'-deoxy-20',20'-difluoro-c'-norvincaleukoblastine
c'-norvincaleukoblastine, 4'-deoxy-20',20'-difluoro-
CHEMBL2110725
chebi:90241 ,
162652-95-1
5bf646324k ,
unii-5bf646324k
vinflunine [inn:ban]
vinflunine [mi]
vinflunine [mart.]
vinflunine [ema epar]
vinflunine [inn]
4'-deoxy-20',20'-difluoro-8'-norvincaleucoblastine
vinflunine [who-dd]
HY-B0628
methyl (2beta,3beta,4beta,5alpha,12beta,19alpha)-4-(acetyloxy)-15-[(12s,14s,16r)-16-(1,1-difluoroethyl)-12-(methoxycarbonyl)-1,10-diazatetracyclo[12.3.1.0(3,11).0(4,9)]octadeca-3(11),4,6,8-tetraen-12-yl]-3-hydroxy-16-methoxy-1-methyl-6,7-didehydroaspidosp
20',20'-difluoro-3',4'-dihydrovinorelbine
vinflunina
vinfluninum
4'-deoxy-20',20'-difluoro-5'-norvincaleukoblastine
DB11641
methyl (1r,9r,10s,11r,12r,19r)-11-acetyloxy-4-[(12s,14s,16r)-16-(1,1-difluoroethyl)-12-methoxycarbonyl-1,10-diazatetracyclo[12.3.1.03,11.04,9]octadeca-3(11),4,6,8-tetraen-12-yl]-12-ethyl-10-hydroxy-5-methoxy-8-methyl-8,16-diazapentacyclo[10.6.1.01,9.02,7.
DTXSID30936722
methyl (1r,9r,10s,11r,12r,19r)-11-(acetyloxy)-4-[(12s,14s,16r)-16-(1,1-difluoroethyl)-12-(methoxycarbonyl)-1,10-diazatetracyclo[12.3.1.0^{3,11}.0^{4,9}]octadeca-3(11),4(9),5,7-tetraen-12-yl]-12-ethyl-10-hydroxy-5-methoxy-8-methyl-8,16-diazapentacyclo[10.6
EN300-33343034
nmdyywfgpimtko-klcpsuaysa-n
AKOS040759183

Research Excerpts

Overview

Vinflunine is a microtubule inhibitor of the vinca alkaloid class approved for the treatment of urothelial bladder carcinoma after a platinum-containing regimen. It is currently the only approved drug for second-line treatment across the European Union.

ExcerptReferenceRelevance
"Vinflunine is a microtubule inhibitor of the vinca alkaloid class approved for the treatment of urothelial bladder carcinoma after a platinum-containing regimen."( Vinflunine in Metastatic Urothelial Carcinoma of the Bladder in Progression after a Platinum-Containing Regimen.
Cicero, G; De Luca, R; Profita, G; Vella, M, 2019
)
3.4
"Vinflunine is a novel tubulin-targeted inhibitor indicated as a single agent for the treatment of bladder cancers after failure of prior platinum-based therapy. "( Better characterization of vinflunine pharmacokinetics variability and exposure/toxicity relationship to improve its use: Analyses from 18 trials.
Ferré, P; Nguyen, L; Pétain, A; Schmitt, A; Zorza, G, 2018
)
2.22
"Vinflunine is a microtubule inhibitor approved in Europe as second-line treatment of advanced transitional cell cancer of the urothelium (TCCU). "( Vinflunine in Advanced Transitional Cell Cancer of the Urothelial Tract: A Potential Option for Maintenance Therapy? A Case Series.
Bernardo, A; Licata, L; Palumbo, R; Pozzi, E; Quaquarini, E; Sottotetti, F; Tagliaferri, B; Teragni, C, 2018
)
3.37
"Vinflunine is a vinca-alkaloid that was specifically developed as second line treatment post-platinum."( [Care of advanced or metastatic bladder cancer in second line: A specific place for vinflunine].
Houédé, N; Milano, G, 2019
)
1.46
"Vinflunine (VFL) is a bifluorinated tubulin-targeted agent of the vinca alkaloids class active in advanced stage breast cancer. "( A phase I clinical and pharmacokinetic study evaluating vinflunine in combination with epirubicin as first-line treatment in metastatic breast cancer.
Bostnavaron, M; Campone, M; Chan, S; Conte, PF; Nguyen, L; Santoro, A, 2014
)
2.09
"Vinflunine (VFL) is a microtubule-targeting drug that suppresses microtubule dynamics, showing anti-metastatic properties both in vitro and in living cancer cells. "( Role of the microtubule-targeting drug vinflunine on cell-cell adhesions in bladder epithelial tumour cells.
Aparicio, LA; Blanco, M; Castosa, R; Figueroa, A; Haz-Conde, M; Rodríguez, M; Valladares, M, 2014
)
2.11
"Vinflunine is a third-generation antimicrotubuline inhibitor and is currently the only approved drug for second-line treatment across the European Union."( Treatment of relapsed urothelial bladder cancer with vinflunine: real-world evidence by the Hellenic Genitourinary Cancer Group.
Adamakis, I; Andreadis, C; Androulakis, N; Athanasiadis, I; Bamias, A; Constantinides, C; Deliveliotis, C; Dellis, A; Dimopoulos, MA; Kalofonos, C; Karavasilis, V; Milaki, G; Mitropoulos, D; Mitsogiannis, I; Molyva, D; Papatsoris, A; Peroukidis, S; Pissanidou, V; Pistamaltzian, N; Stravodimos, K; Tzannis, K; Varkarakis, I, 2016
)
1.41
"Vinflunine is a derivative of vinorelbine that has been studied in MPM as first-line agent."( Vinca alkaloids in the therapeutic management of malignant pleural mesothelioma.
Ceresoli, GL; Zucali, PA, 2015
)
1.14
"Vinflunine is an efficient and tolerable second line treatment in advanced TCCU."( VICTOR: Vinflunine in advanced metastatic transitional cell carcinoma of the urothelium: A retrospective analysis of the use of vinflunine in multi-centre real life setting as second line chemotherapy through Free of Charge Programme for patients in the U
Ansari, J; Chauhan, S; Elander, NO; Faust, G; Huddart, R; Hussain, SA; Jackson, RJ; Lyons, J; McMenemin, R; Pickering, LM; Power, DG; Vilarino-Varlela, M; Wylie, J, 2017
)
1.61
"Vinflunine is an innovative microtubule inhibitor of the vinca alkaloid class with distinct tubulin-binding properties. "( Antitumor activity of vinflunine: effector pathways and potential for synergies.
Barret, JM; Braguer, D; Kruczynski, A; McDaid, H, 2008
)
2.1
"Vinflunine is a novel microtubule inhibitor of the vinca alkaloid class currently in development for the treatment of advanced transitional cell carcinoma of the urothelium (TCCU) and other solid tumors. "( Clinical activity of vinflunine in transitional cell carcinoma of the urothelium and other solid tumors.
Bellmunt, J; Delgado, FM; George, C, 2008
)
2.11
"Vinflunine is an active and well-tolerated agent as third-line treatment of patients with MBC after failure of anthracycline- and taxane-based therapy. "( Phase 2 study of single-agent IV vinflunine as third-line treatment of metastatic breast cancer after failure of anthracycline-/taxane-based chemotherapy.
Alberts, AS; Ben Ayed, F; Campone, M; Caroff-Paraïso, I; Chan, S; Cortés-Funes, H; Fumoleau, P; Pouget, JC; Slabber, CF; Taleb, AB; Tubiana-Hulin, M, 2009
)
2.08
"Vinflunine (VFL) is a new microtubule inhibitor that has activity against transitional cell carcinoma of urothelial tract (TCCU). "( Phase III trial of vinflunine plus best supportive care compared with best supportive care alone after a platinum-containing regimen in patients with advanced transitional cell carcinoma of the urothelial tract.
Bellmunt, J; Carles, J; Caty, A; Culine, S; Daugaard, G; Delgado, FM; Demkov, T; Hurteloup, P; Jagiello-Gruszfeld, A; Karyakin, O; Komyakov, B; Morsli, N; Salhi, Y; Sengelov, L; Théodore, C; von der Maase, H; Winquist, E, 2009
)
2.12
"Vinflunine is a novel vinca alkaloid with promising single agent clinical activity. "( Phase I trial of vinflunine and pemetrexed in refractory solid tumors.
Buie, L; Chiu, WK; Davies, J; Dees, EC; Ivanova, A; Keller, K; O'Neil, B; Sanoff, HK; Stinchcombe, TE; Walko, C, 2011
)
2.15
"Vinflunine is a new microtubule inhibitor with preclinical activity in small cell lung cancer (SCLC). "( Phase II trial of vinflunine in relapsed small cell lung cancer.
Burris, HA; Clark, B; Greco, FA; Hainsworth, JD; Lane, CM; Spigel, DR, 2010
)
2.14
"Vinflunine is a novel bifluorinated vinca alkaloid that appears to differ from other class members in terms of its tubulin-binding properties and inhibitory effects on microtubule dynamics. "( Vinflunine.
Frampton, JE; Moen, MD, 2010
)
3.25
"Vinflunine is a new vinca alkaloid for the treatment of advanced staged solid tumors. "( Vinflunine: review of a new vinca alkaloid and its potential role in oncology.
Ng, JS, 2011
)
3.25
"Vinflunine is a novel third-generation bifluorinated semisynthetic vinca alkaloid that has been shown to have activity against a variety of solid tumor types including advanced transitional cell carcinoma of the urothelium. "( Vinflunine: a fluorinated vinca alkaloid for bladder cancer therapy.
Gerullis, H, 2011
)
3.25
"Vinflunine is a new microtubule inhibitor of the vinca-alkaloid family. "( Phase I dose-escalation study of vinflunine hard capsules administered twice a day for 2 consecutive days every week in patients with advanced/metastatic solid tumors.
Bennouna, J; Calvo, E; Cortes, J; Dyck, J; Ferre, P; Hiret, S; Pétain, A; Rodon, J; Senellart, H; Van den Brande, J; Vermorken, JB, 2012
)
2.1
"Vinflunine is a new-generation microtubule inhibitor, which is currently registered in Europe and in some countries elsewhere as an intravenous formulation for the second-line treatment of transitional urothelial cell carcinoma. "( Vinflunine oral pharmacokinetics and absolute bioavailability of soft and hard gelatin capsules: results of two phase I trials.
Bennouna, J; Bougaret, J; Brandely-Talbot, M; Delord, JP; Ferré, P; Mourey, L, 2012
)
3.26
"Vinflunine is a novel tubulin-targeted agent that is currently indicated as a monotherapy in bladder cancer patients. "( Phase I and pharmacokinetic study of IV vinflunine in cancer patients with liver dysfunction.
Bennouna, J; Delord, JP; Favrel, S; Ferré, P; Fumoleau, P; Pinel, MC; Ravaud, A; Saliba, F, 2013
)
2.1
"Vinflunine ditartrate is a microtubule inhibitor belonging to the vinca alkaloid family. "( Phase I dose-escalation study of oral vinflunine administered once daily for 6 weeks every 8 weeks in patients with advanced/metastatic solid tumours.
Delord, JP; Lefresne, F; Pétain, A; Pouget, JC; Ravaud, A; Tourani, JM, 2013
)
2.1
"Vinflunine is a novel vinca alkaloid obtained by semi-synthesis using super-acidic chemistry to selectively introduce two fluorine atoms at the 20' position of vinorelbine. "( Phase I and pharmacokinetic study of the new vinca alkaloid vinflunine administered as a 10-min infusion every 3 weeks in patients with advanced solid tumours.
Armand, JP; Bennouna, J; Campone, M; Delgado, FM; Fumoleau, P; Marty, M; Puozzo, C; Raymond, E, 2003
)
2
"Vinflunine is a novel fluorinated Vinca alkaloid currently in Phase II clinical trials, which in preclinical studies exhibited superior antitumor activity to that of two clinically useful Vinca alkaloids, vinorelbine and vinblastine. "( The effects of vinflunine, vinorelbine, and vinblastine on centromere dynamics.
Hill, BT; Jordan, MA; Okouneva, T; Wilson, L, 2003
)
2.11
"Vinflunine is a novel Vinca alkaloid currently undergoing Phase II clinical trials, which have previously demonstrated anti-vascular effects in a transplantable murine colon adenocarcinoma model. "( Vinflunine potentiates the activity of cisplatin but not 5-fluorouracil in a transplantable murine adenocarcinoma model.
Bibby, MC; Cooper, PA; Double, JA; Gyselinck, N; Hill, BT; Shnyder, SD,
)
3.02
"Vinflunine is a novel vinca alkaloid developed through the selective modification of vinorelbine using super-acidic chemistry. "( Phase I study of vinflunine administered as a 10-minute infusion on days 1 and 8 every 3 weeks.
Fumoleau, P; Geldart, T; Johnson, P; Judson, I; Nguyen, L; Pinel, MC, 2006
)
2.12
"Vinflunine is a novel vinca alkaloid which has shown remarkable improvement in efficiency and reduced side-effects in both in vitro and in vivo studies."( Head and neck carcinoma cell lines are sensitive to vinflunine in vitro.
Erjala, K; Grénman, R; Kulmala, J; Raitanen, M,
)
1.1
"Vinflunine (VFL) is a novel third generation Vinca alkaloid with superior antitumour activity in preclinical models and an anticipated more favourable toxicity profile compared to the other Vinca alkaloids."( Cell cycle effects of vinflunine, the most recent promising Vinca alkaloid, and its interaction with radiation, in vitro.
Breillout, F; De Pooter, CM; Korst, AE; Lambrechts, HA; Lardon, F; Pattyn, GG; Pauwels, B; Simoens, C; Vermorken, JB, 2006
)
2.09
"Vinflunine is an active agent for the treatment of platinum-pretreated bladder cancer, and these results warrant further investigation in phase III trials, either as monotherapy or in combination with other agents as treatment of advanced/metastatic TCC of the bladder."( A phase II study of vinflunine in bladder cancer patients progressing after first-line platinum-containing regimen.
Bui, B; Culine, S; De Santis, M; Delgado, FM; Demkow, T; James, N; Longerey, B; Lorenz, J; Rolland, F; Theodore, C, 2006
)
1.38
"Vinflunine is an active agent with acceptable tolerance in the management of MBC patients previously treated with (A/T)-based regimens."( Vinflunine: a new active drug for second-line treatment of advanced breast cancer. Results of a phase II and pharmacokinetic study in patients progressing after first-line anthracycline/taxane-based chemotherapy.
Aslanis, V; Bourbouloux, E; Campone, M; Ciruelos, E; Colin, C; Cortes-Funes, H; Delgado, FM; Fumoleau, P; Martin, M; Mendiola, C; Slabber, CF; Vorobiof, D, 2006
)
2.5
"Vinflunine is a novel second generation of Vinca alkaloid. "( Vinflunine: clinical perspectives of an emerging anticancer agent.
Chow, LW; Yuen-Yuen Ong, E; Yun-San Yip, A, 2008
)
3.23
"Vinflunine (VFL) is a novel derivative of vinorelbine (NVB, Navelbine), which has shown markedly superior antitumor activity to NVB, in various experimental animal models. "( Vinflunine (20',20'-difluoro-3',4'-dihydrovinorelbine), a novel Vinca alkaloid, which participates in P-glycoprotein (Pgp)-mediated multidrug resistance in vivo and in vitro.
Barret, JM; Etievant, C; Hill, BT; Kruczynski, A; Perrin, D, 1998
)
3.19
"Vinflunine is a novel Vinca alkaloid presently in Phase I clinical trials. "( Novel actions of the antitumor drugs vinflunine and vinorelbine on microtubules.
Bellman, K; Hill, BT; Jordan, MA; Ngan, VK; Panda, D; Wilson, L, 2000
)
2.02
"Vinflunine (VFL) is a novel Vinca alkaloid with markedly superior experimental in vivo antitumour activity to its parent molecule, vinorelbine (Navelbine, NVB), against a panel of murine and human tumours. "( Markedly diminished drug resistance-inducing properties of vinflunine (20',20'-difluoro-3',4'-dihydrovinorelbine) relative to vinorelbine, identified in murine and human tumour cells in vivo and in vitro.
Barret, JM; Etiévant, C; Hill, BT; Kavallaris, M; Kruczynski, A; Tait, AS, 2001
)
2
"Vinflunine is a new Vinca alkaloid uniquely fluorinated, by the use of superacid chemistry, in a little exploited region of the catharanthine moiety. "( Vinflunine, the latest Vinca alkaloid in clinical development. A review of its preclinical anticancer properties.
Hill, BT; Kruczynski, A, 2001
)
3.2

Effects

Vinflunine (VFL) has been approved in the European Union for second-line treatment of advanced transitional cell carcinoma of the urothelial tract (TCCU) In patients who progress after a platinum based regimen.

ExcerptReferenceRelevance
"Vinflunine has a low level of activity in the treatment of refractory metastatic prostate cancer, and should not be further developed for this indication."( Single agent vinflunine in the salvage treatment of patients with castration-resistant prostate cancer: a phase II trial of the Sarah Cannon research consortium.
Burris, HA; Crane, EJ; Gandhi, JG; Greco, FA; Hainsworth, JD; Lane, CM; Meluch, AA; Spigel, DR; Stipanov, MA, 2010
)
1.45
"Vinflunine has shown significant activity in vivo, which involves its antimitotic, antiangiogenic, and antivascular properties."( Pharmacokinetics, metabolites, and preclinical safety of vinflunine.
Lobert, S; Puozzo, C, 2008
)
1.31
"Vinflunine (Javlor) has shown significant antitumour activity in advanced non-small cell lung cancer (NSCLC). "( Phase I and pharmacokinetic study of IV vinflunine in combination with gemcitabine for treatment of advanced non-small cell lung cancer in Chemonaive patients.
Bennouna, J; Favrel, S; Lemarie, E; Pinel, MC; Pouget, JC; Senellart, H; Tourani, JM; Tournoux-Facon, C, 2011
)
2.08
"Vinflunine has been approved for second-line treatment in this indication."( Long-term response in advanced bladder cancer involving the use of temsirolimus and vinflunine after platin resistance.
Arndt, C; Ecke, TH; Gerullis, H; Heidari, M; Janusch, B; Oniani, J; Otto, T, 2011
)
1.32
"Vinflunine (VFL) has been approved in the European Union for second-line treatment of advanced transitional cell carcinoma of the urothelial tract (TCCU) in patients who progress after a platinum based regimen. "( Optimisation of the size variation threshold for imaging evaluation of response in patients with platinum-refractory advanced transitional cell carcinoma of the urothelium treated with vinflunine.
Bellmunt, J; Choueiri, TK; Fougeray, R; Krajewski, KM; Pons, F; Rosenberg, JE; Salhi, Y; Schutz, FA, 2012
)
2.01
"Vinflunine activity has been documented in terms of both survival prolongation and tumor growth inhibition, with definite superiority over vinorelbine being shown in each tumor model evaluated."( Preclinical in vivo antitumor activity of vinflunine, a novel fluorinated Vinca alkaloid.
Colpaert, F; Fahy, J; Hill, BT; Kruczynski, A; Mouillard, P; Tarayre, JP, 1998
)
1.29

Treatment

Vinflunine treatment of these cells resulted in apoptosis characterized by DNA fragmentation and proteolytic cleavage of poly-(ADP-ribose) polymerase.

ExcerptReferenceRelevance
"Vinflunine is the only treatment approved in this setting by the European Medicines Agency and taxanes are also widely used in second line."( A randomized phase II/III study of cabazitaxel versus vinflunine in metastatic or locally advanced transitional cell carcinoma of the urothelium (SECAVIN).
Anido, U; Bellmunt, J; Collado, R; De Wit, R; Fernández Calvo, O; González Graguera, MB; González Larriba, JL; González-Billalabeitia, E; Grande, E; Kerst, JM; Los, M; Maciá, S; Medina, A; Morales-Barrera, R; Perez-Gracia, JL; Pujol, E; Rubio, G; Van den Eertwegh, AJM; Vázquez, F, 2017
)
1.42
"Vinflunine treatment of these cells resulted in apoptosis characterized by DNA fragmentation and proteolytic cleavage of poly-(ADP-ribose) polymerase."( Characterization of cell death induced by vinflunine, the most recent Vinca alkaloid in clinical development.
Chansard, N; Duflos, A; Etiévant, C; Hill, BT; Kruczynski, A; Perrin, D, 2002
)
1.3

Toxicity

ExcerptReferenceRelevance
" It has been shown to have predictable and manageable adverse effects, such as neutropenia, anemia, constipation and fatigue."( Vinflunine: drug safety evaluation of this novel synthetic vinca alkaloid.
Bellmunt, J; Choueiri, TK; Rosenberg, JE; Schutz, FA, 2011
)
1.81
" The most commonly reported adverse events of any grade were constipation 70."( Safety and effectiveness of vinflunine in patients with metastatic transitional cell carcinoma of the urothelial tract after failure of one platinum-based systemic therapy in clinical practice.
Castellano, D; Chirivella, I; de Velasco, G; Fernández, O; García-Carbonero, I; González, MB; Grande, E; López-Criado, P; Mohedano, N; Puente, J, 2014
)
0.7
" To assess the effectiveness and safety of vinflunine treatment, progression-free survival, overall survival, and adverse events were registered."( Effectiveness, toxicity, and economic evaluation of vinflunine for the treatment of patients with transitional cell carcinoma in the Spanish outpatient setting.
Alós-Almiñana, M; Climente-Martí, M; Ferriols-Lisart, F; Guglieri-López, B; Pérez-Pitarch, A; Porta-Oltra, B, 2015
)
0.93
" In risk groups based on 0-3 presence of adverse prognostic factors (PS ≥ 1, haemoglobin ≤ 10 g/dl and liver metastasis), median OS: 13."( Efficacy and safety of Vinflunine for advanced or metastatic urothelial carcinoma in routine practice based on the French multi-centre CURVE study.
Di Palma, M; Guillot, A; Médioni, J; Spaeth, D; Théodore, C, 2016
)
0.74
" The drug is safe with gastro-intestinal and haematological prophylaxis."( Efficacy and safety of Vinflunine for advanced or metastatic urothelial carcinoma in routine practice based on the French multi-centre CURVE study.
Di Palma, M; Guillot, A; Médioni, J; Spaeth, D; Théodore, C, 2016
)
0.74
" There were three serious adverse events namely two sudden deaths and one grade 4 thrombocytopenia."( Safety of Vinflunine in Patients with Advanced Urothelial Carcinoma Refractory to Platinum-based Chemotherapy: A Prospective Pilot Study.
Abbas, N; Abdel-Kader, Y; Abdel-Malek, R; Hamada, E; Ismail, M; Shohdy, KS, 2019
)
0.92

Pharmacokinetics

The high bioavailability and low inter-individual variability are favourable pharmacokinetic properties, which could be valuable for further clinical development of oral vinflunine. An eventual mutual pharmacokinetics drug-drug interaction when vin Flunine and cisplatin were coadministered was also evaluated.

ExcerptReferenceRelevance
" The established method has been successfully applied to a pharmacokinetic study of vinflunine in rats."( Determination of vinflunine in rat plasma by liquid chromatography-electrospray ionization mass spectrometry for a pharmacokinetic study.
Chen, Y; Liu, X; Wang, G; Wang, Y; Zhao, X; Zhong, J, 2006
)
0.9
" The pharmacokinetic properties and metabolism of vinflunine in animals and in human subjects are also discussed, together with an analysis of potential drug-drug interactions and the influence of age, liver dysfunction, or renal dysfunction on the overall activity of vinflunine."( Pharmacokinetics, metabolites, and preclinical safety of vinflunine.
Lobert, S; Puozzo, C, 2008
)
0.84
" An eventual mutual pharmacokinetic drug-drug interaction when vinflunine and cisplatin were coadministered was also evaluated."( Phase I/II and pharmacokinetic study of intravenous vinflunine in combination with cisplatin for the treatment of chemonaive patients with advanced non-small-cell lung cancer.
Krzakowski, M; Lopez-Vivanco, G; Pinel, MC; Pouget, JC; Puozzo, C; Ramlau, R; Rosell, R; Souquet, PJ; Sun, XS, 2010
)
0.85
" Pharmacokinetic analysis supported the absence of mutual pharmacokinetic interaction when vinflunine and cisplatin are given in combination."( Phase I/II and pharmacokinetic study of intravenous vinflunine in combination with cisplatin for the treatment of chemonaive patients with advanced non-small-cell lung cancer.
Krzakowski, M; Lopez-Vivanco, G; Pinel, MC; Pouget, JC; Puozzo, C; Ramlau, R; Rosell, R; Souquet, PJ; Sun, XS, 2010
)
0.83
"A phase I and pharmacokinetic study was conducted to determine the maximum tolerated dose and to establish the recommended dose of vinflunine (VFL) administered on day 1 every 21 days combined with gemcitabine given on days 1 and 8 every 3 weeks."( Phase I and pharmacokinetic study of IV vinflunine in combination with gemcitabine for treatment of advanced non-small cell lung cancer in Chemonaive patients.
Bennouna, J; Favrel, S; Lemarie, E; Pinel, MC; Pouget, JC; Senellart, H; Tourani, JM; Tournoux-Facon, C, 2011
)
0.84
" The validated assay was applied to a pharmacokinetic study of vinflunine in plasma following the administration of a single vinflunine injection (2 mg/kg)."( A validated LC-MS/MS method for the determination of vinflunine in plasma and its application to pharmacokinetic studies.
Hong-Min, L; Ming, Y; Pin, H; Qin, L, 2012
)
0.87
"Each pharmacokinetic trial was conducted according to a randomized cross-over design."( Vinflunine oral pharmacokinetics and absolute bioavailability of soft and hard gelatin capsules: results of two phase I trials.
Bennouna, J; Bougaret, J; Brandely-Talbot, M; Delord, JP; Ferré, P; Mourey, L, 2012
)
1.82
"The high bioavailability and low inter-individual variability are favourable pharmacokinetic properties, which could be valuable for further clinical development of oral vinflunine."( Vinflunine oral pharmacokinetics and absolute bioavailability of soft and hard gelatin capsules: results of two phase I trials.
Bennouna, J; Bougaret, J; Brandely-Talbot, M; Delord, JP; Ferré, P; Mourey, L, 2012
)
2.02
"This phase I and pharmacokinetic study was designed to determine the maximum tolerated dose and to establish the RD of VFL in combination with carboplatin."( Phase I and pharmacokinetic study of IV vinflunine in combination with carboplatin in chemonaive patients with advanced non-small cell lung cancer.
Ferre, P; Pinel, MC; Robinet, G; Tourani, JM; Tournoux-Facon, C, 2012
)
0.65
" We conducted a phase I study combining VFL with epirubicin (EPR) to establish the recommended dose (RD), to evaluate the safety and efficacy profiles and to investigate potential pharmacokinetic (PK) drug-drug interaction (DDI)."( A phase I clinical and pharmacokinetic study evaluating vinflunine in combination with epirubicin as first-line treatment in metastatic breast cancer.
Bostnavaron, M; Campone, M; Chan, S; Conte, PF; Nguyen, L; Santoro, A, 2014
)
0.65

Compound-Compound Interactions

The results revealed synergistic cytotoxicity when vinflunine was combined with cisplatin, mitomycin C, doxorubicin or 5-fluorouracil. We propose to define the recommended dose of vin Flunine in combination with gemcitabine for treatment of advanced NSCLC.

ExcerptReferenceRelevance
"The results revealed synergistic cytotoxicity when vinflunine was combined with cisplatin, mitomycin C, doxorubicin or 5-fluorouracil."( In vitro synergistic effects of vinflunine, a novel fluorinated vinca alkaloid, in combination with other anticancer drugs.
Barret, JM; Etiévant, C; Hill, BT, 2000
)
0.84
"A multicenter phase I/II trial of vinflunine administered in combination with cisplatin at 80 mg/m(2) was conducted in order to determine the dose-limiting toxicities, the maximum tolerated dose, and the recommended dose of the combination."( Phase I/II and pharmacokinetic study of intravenous vinflunine in combination with cisplatin for the treatment of chemonaive patients with advanced non-small-cell lung cancer.
Krzakowski, M; Lopez-Vivanco, G; Pinel, MC; Pouget, JC; Puozzo, C; Ramlau, R; Rosell, R; Souquet, PJ; Sun, XS, 2010
)
0.89
"The recommended dose was established at cisplatin 80 mg/m2 combined with vinflunine 320 mg/m(2)."( Phase I/II and pharmacokinetic study of intravenous vinflunine in combination with cisplatin for the treatment of chemonaive patients with advanced non-small-cell lung cancer.
Krzakowski, M; Lopez-Vivanco, G; Pinel, MC; Pouget, JC; Puozzo, C; Ramlau, R; Rosell, R; Souquet, PJ; Sun, XS, 2010
)
0.84
" We propose to define the recommended dose of vinflunine in combination with gemcitabine for treatment of advanced NSCLC in chemonaive patients."( Phase I and pharmacokinetic study of IV vinflunine in combination with gemcitabine for treatment of advanced non-small cell lung cancer in Chemonaive patients.
Bennouna, J; Favrel, S; Lemarie, E; Pinel, MC; Pouget, JC; Senellart, H; Tourani, JM; Tournoux-Facon, C, 2011
)
0.9
"A phase I and pharmacokinetic study was conducted to determine the maximum tolerated dose and to establish the recommended dose of vinflunine (VFL) administered on day 1 every 21 days combined with gemcitabine given on days 1 and 8 every 3 weeks."( Phase I and pharmacokinetic study of IV vinflunine in combination with gemcitabine for treatment of advanced non-small cell lung cancer in Chemonaive patients.
Bennouna, J; Favrel, S; Lemarie, E; Pinel, MC; Pouget, JC; Senellart, H; Tourani, JM; Tournoux-Facon, C, 2011
)
0.84
" The recommended dose was established at the dose of VFL 320 mg/m² combined with gemcitabine 1000 mg/m²."( Phase I and pharmacokinetic study of IV vinflunine in combination with gemcitabine for treatment of advanced non-small cell lung cancer in Chemonaive patients.
Bennouna, J; Favrel, S; Lemarie, E; Pinel, MC; Pouget, JC; Senellart, H; Tourani, JM; Tournoux-Facon, C, 2011
)
0.64
"The combination of VFL 320 mg/m² administered on day 1 combined with gemcitabine 1000 mg/m² given on days 1 and 8 every 3 weeks is established as the RD and was shown to be active in these chemonaive NSCLC patients."( Phase I and pharmacokinetic study of IV vinflunine in combination with gemcitabine for treatment of advanced non-small cell lung cancer in Chemonaive patients.
Bennouna, J; Favrel, S; Lemarie, E; Pinel, MC; Pouget, JC; Senellart, H; Tourani, JM; Tournoux-Facon, C, 2011
)
0.64
"A phase I study was performed to determine the maximal tolerated dose (MTD), recommended dose (RD), safety and efficacy of vinflunine when combined with capecitabine in patients with metastatic breast cancer (MBC) previously treated with anthracyclines and taxanes, with pharmacokinetic blood sampling to test potential drug-drug interactions."( A phase I study of vinflunine in combination with capecitabine in patients with metastatic breast cancer previously treated with anthracyclines and taxanes.
Bonneterre, J; Bourbouloux, E; Campone, M; Fumoleau, P; Isambert, N; Milano, G; Roché, H, 2012
)
0.91
" The risk of clinical significant drug-drug interaction was considered weak."( A phase I study of vinflunine in combination with capecitabine in patients with metastatic breast cancer previously treated with anthracyclines and taxanes.
Bonneterre, J; Bourbouloux, E; Campone, M; Fumoleau, P; Isambert, N; Milano, G; Roché, H, 2012
)
0.71
" We propose to define the recommended dose (RD) of VFL in combination with carboplatin in advanced NSCLC patients."( Phase I and pharmacokinetic study of IV vinflunine in combination with carboplatin in chemonaive patients with advanced non-small cell lung cancer.
Ferre, P; Pinel, MC; Robinet, G; Tourani, JM; Tournoux-Facon, C, 2012
)
0.65
"This phase I and pharmacokinetic study was designed to determine the maximum tolerated dose and to establish the RD of VFL in combination with carboplatin."( Phase I and pharmacokinetic study of IV vinflunine in combination with carboplatin in chemonaive patients with advanced non-small cell lung cancer.
Ferre, P; Pinel, MC; Robinet, G; Tourani, JM; Tournoux-Facon, C, 2012
)
0.65
" The RD was established at the dose of VFL (320 mg/m(2)) combined with carboplatin AUC5."( Phase I and pharmacokinetic study of IV vinflunine in combination with carboplatin in chemonaive patients with advanced non-small cell lung cancer.
Ferre, P; Pinel, MC; Robinet, G; Tourani, JM; Tournoux-Facon, C, 2012
)
0.65
"To determine the recommended dose (RD) of vinflunine in combination with trastuzumab in human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer (MBC) and to investigate potential pharmacokinetic (PK) interactions."( A phase 1 study of vinflunine in combination with trastuzumab for the treatment for HER2-positive metastatic breast cancer.
Ferré, P; Paridaens, R; Pinel, MC; Rixe, O; Roche, H; Wildiers, H; Zorza, G, 2012
)
0.97
"In the first part of the study, two dose levels of vinflunine given every 3 weeks were explored (280 and 320 mg/m(2)) combined with trastuzumab (4 mg/kg loading dose and 2 mg/kg weekly)."( A phase 1 study of vinflunine in combination with trastuzumab for the treatment for HER2-positive metastatic breast cancer.
Ferré, P; Paridaens, R; Pinel, MC; Rixe, O; Roche, H; Wildiers, H; Zorza, G, 2012
)
0.96
"The RD of vinflunine in combination with the standard regimen of trastuzumab is 280 mg/m(2) every 3 weeks."( A phase 1 study of vinflunine in combination with trastuzumab for the treatment for HER2-positive metastatic breast cancer.
Ferré, P; Paridaens, R; Pinel, MC; Rixe, O; Roche, H; Wildiers, H; Zorza, G, 2012
)
1.11
" A potential pharmacokinetic drug-drug interaction was also investigated."( Phase I dose-escalation study of oral vinflunine in combination with erlotinib in pre-treated and unselected EGFR patients with locally advanced or metastatic non-small-cell lung cancer.
Bennouna, J; Dansin, E; Favrel, S; Hiret, S; Kowalski, D; Krzakowski, M; Penel, N; Tourani, JM, 2014
)
0.67
" We conducted a phase I study combining VFL with epirubicin (EPR) to establish the recommended dose (RD), to evaluate the safety and efficacy profiles and to investigate potential pharmacokinetic (PK) drug-drug interaction (DDI)."( A phase I clinical and pharmacokinetic study evaluating vinflunine in combination with epirubicin as first-line treatment in metastatic breast cancer.
Bostnavaron, M; Campone, M; Chan, S; Conte, PF; Nguyen, L; Santoro, A, 2014
)
0.65

Bioavailability

The high bioavailability and low inter-individual variability are favourable pharmacokinetic properties, which could be valuable for further clinical development of oral vinflunine.

ExcerptReferenceRelevance
"The absolute oral bioavailability was investigated in patients through two consecutive trials: the first trial used soft gelatin capsules filled with solubilized vinflunine (SLCaps), while the second study investigated hard gelatin capsules containing vinflunine as a formulated powder (HPCaps)."( Vinflunine oral pharmacokinetics and absolute bioavailability of soft and hard gelatin capsules: results of two phase I trials.
Bennouna, J; Bougaret, J; Brandely-Talbot, M; Delord, JP; Ferré, P; Mourey, L, 2012
)
2.02
" A pharmacokinetic analysis was conducted for each patient and route of dosing to derive the absolute oral bioavailability of SLCaps and HPCaps."( Vinflunine oral pharmacokinetics and absolute bioavailability of soft and hard gelatin capsules: results of two phase I trials.
Bennouna, J; Bougaret, J; Brandely-Talbot, M; Delord, JP; Ferré, P; Mourey, L, 2012
)
1.82
" The mean absolute bioavailability was high, at 58."( Vinflunine oral pharmacokinetics and absolute bioavailability of soft and hard gelatin capsules: results of two phase I trials.
Bennouna, J; Bougaret, J; Brandely-Talbot, M; Delord, JP; Ferré, P; Mourey, L, 2012
)
1.82
"The high bioavailability and low inter-individual variability are favourable pharmacokinetic properties, which could be valuable for further clinical development of oral vinflunine."( Vinflunine oral pharmacokinetics and absolute bioavailability of soft and hard gelatin capsules: results of two phase I trials.
Bennouna, J; Bougaret, J; Brandely-Talbot, M; Delord, JP; Ferré, P; Mourey, L, 2012
)
2.02

Dosage Studied

Pemetrexed was added to vinflunine dosed at 280 mg/m2 on day 1 of a 21-day cycle. The pharmacokinetic analysis demonstrated the adequacy of the flat-fixed dosing regimen. No correlation between clearance of vin Flunine and body surface area was evidenced.

ExcerptRelevanceReference
" These studies were prompted by the observation that the energetics of vinca alkaloid-induced tubulin spiral polymers, or spiraling potential, is inversely related to their clinical dosage and are aimed at the long-term goal of developing the ability to predict the cytotoxic and antineoplastic properties of antimitotic drugs."( Vinca alkaloid-induced tubulin spiral formation correlates with cytotoxicity in the leukemic L1210 cell line.
Correia, JJ; Duflos, A; Etievant, C; Fahy, J; Hill, BT; Lobert, S, 2000
)
0.31
"Given the marked toxicity in our patient population, the combination of vinflunine and erlotinib cannot be recommended for further study with these dosing schemas."( A phase I evaluation of the combination of vinflunine and erlotinib in patients with refractory solid tumors.
Buie, L; Chiu, WK; Davies, JM; Dees, EC; Irvin, W; Ivanova, A; Keller, K; O'Neil, BH; Sanoff, HK; Stinchcombe, TE; Walko, C, 2011
)
0.86
" The pharmacokinetic analysis demonstrated the adequacy of the flat-fixed dosing regimen, as no correlation between clearance of vinflunine and body surface area was evidenced."( Phase I dose-escalation study of vinflunine hard capsules administered twice a day for 2 consecutive days every week in patients with advanced/metastatic solid tumors.
Bennouna, J; Calvo, E; Cortes, J; Dyck, J; Ferre, P; Hiret, S; Pétain, A; Rodon, J; Senellart, H; Van den Brande, J; Vermorken, JB, 2012
)
0.87
" Patients received 120 mg/m2 of either oral (SLCaps or HPCaps) or intravenous vinflunine on day 1, followed by the alternate dosing route after a 2-week washout period."( Vinflunine oral pharmacokinetics and absolute bioavailability of soft and hard gelatin capsules: results of two phase I trials.
Bennouna, J; Bougaret, J; Brandely-Talbot, M; Delord, JP; Ferré, P; Mourey, L, 2012
)
2.05
" Vinflunine was dosed at 280 mg/m for the first dose and 320 mg/m every 3 weeks thereafter."( Combined treatment with pazopanib and vinflunine in patients with advanced urothelial carcinoma refractory after first-line therapy.
Arndt, C; Ecke, TH; Eimer, C; Georgas, E; Gerullis, H; Otto, T, 2013
)
1.57
" Dosing of vinflunine, tumor assessments and concomitant medications followed physician's routine clinical practice."( Vinflunine in routine clinical practice for the treatment of advanced or metastatic urothelial cell carcinoma - data from a prospective, multicenter experience.
de Geeter, P; de Schultz, W; Goebell, PJ; Hegele, A; Matz, U; Retz, M, 2015
)
2.25
" Pemetrexed was added to vinflunine dosed at 280 mg/m2 on day 1 of a 21-day cycle."( Combined treatment with pemetrexed and vinflunine in patients with metastatic urothelial cell carcinoma after prior platinum-containing chemotherapy - results of an exploratory phase I study.
Agerbæk, M; Pappot, H; Ullén, A; von der Maase, H, 2018
)
1.05
[information is derived through text-mining from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Roles (1)

RoleDescription
antineoplastic agentA substance that inhibits or prevents the proliferation of neoplasms.
[role information is derived from Chemical Entities of Biological Interest (ChEBI), Hastings J, Owen G, Dekker A, Ennis M, Kale N, Muthukrishnan V, Turner S, Swainston N, Mendes P, Steinbeck C. (2016). ChEBI in 2016: Improved services and an expanding collection of metabolites. Nucleic Acids Res]

Drug Classes (6)

ClassDescription
organic heteropentacyclic compound
organic heterotetracyclic compound
semisynthetic derivativeAny organic molecular entity derived from a natural product by partial chemical synthesis.
methyl esterAny carboxylic ester resulting from the formal condensation of a carboxy group with methanol.
acetate esterAny carboxylic ester where the carboxylic acid component is acetic acid.
vinca alkaloidA group of indole-indoline dimers which are alkaloids obtained from the Vinca genus of plants, together with semi-synthetic and fully synthetic analogues.
[compound class information is derived from Chemical Entities of Biological Interest (ChEBI), Hastings J, Owen G, Dekker A, Ennis M, Kale N, Muthukrishnan V, Turner S, Swainston N, Mendes P, Steinbeck C. (2016). ChEBI in 2016: Improved services and an expanding collection of metabolites. Nucleic Acids Res]

Bioassays (6)

Assay IDTitleYearJournalArticle
AID588213Literature-mined compound from Fourches et al multi-species drug-induced liver injury (DILI) dataset, effect in non-rodents2010Chemical research in toxicology, Jan, Volume: 23, Issue:1
Cheminformatics analysis of assertions mined from literature that describe drug-induced liver injury in different species.
AID588211Literature-mined compound from Fourches et al multi-species drug-induced liver injury (DILI) dataset, effect in humans2010Chemical research in toxicology, Jan, Volume: 23, Issue:1
Cheminformatics analysis of assertions mined from literature that describe drug-induced liver injury in different species.
AID736172Cytotoxicity against human SK-N-SH cells assessed as cell death at 80 uM after 72 hrs by MTT assay2013Journal of medicinal chemistry, Mar-28, Volume: 56, Issue:6
A synthetic dolastatin 10 analogue suppresses microtubule dynamics, inhibits cell proliferation, and induces apoptotic cell death.
AID736171Cytotoxicity against human SK-N-SH cells assessed as cell death at 50 uM after 72 hrs by MTT assay2013Journal of medicinal chemistry, Mar-28, Volume: 56, Issue:6
A synthetic dolastatin 10 analogue suppresses microtubule dynamics, inhibits cell proliferation, and induces apoptotic cell death.
AID588212Literature-mined compound from Fourches et al multi-species drug-induced liver injury (DILI) dataset, effect in rodents2010Chemical research in toxicology, Jan, Volume: 23, Issue:1
Cheminformatics analysis of assertions mined from literature that describe drug-induced liver injury in different species.
AID361671Cytotoxicity against human A549 cells by SRB assay2008Bioorganic & medicinal chemistry letters, Aug-15, Volume: 18, Issue:16
Synthesis and biological evaluation of C-12' substituted vinflunine derivatives.
[information is prepared from bioassay data collected from National Library of Medicine (NLM), extracted Dec-2023]

Research

Studies (166)

TimeframeStudies, This Drug (%)All Drugs %
pre-19900 (0.00)18.7374
1990's6 (3.61)18.2507
2000's55 (33.13)29.6817
2010's97 (58.43)24.3611
2020's8 (4.82)2.80
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Market Indicators

Research Demand Index: 44.50

According to the monthly volume, diversity, and competition of internet searches for this compound, as well the volume and growth of publications, there is estimated to be strong demand-to-supply ratio for research on this compound.

MetricThis Compound (vs All)
Research Demand Index44.50 (24.57)
Research Supply Index5.41 (2.92)
Research Growth Index5.20 (4.65)
Search Engine Demand Index69.42 (26.88)
Search Engine Supply Index2.00 (0.95)

This Compound (44.50)

All Compounds (24.57)

Study Types

Publication TypeThis drug (%)All Drugs (%)
Trials51 (29.65%)5.53%
Reviews36 (20.93%)6.00%
Case Studies6 (3.49%)4.05%
Observational2 (1.16%)0.25%
Other77 (44.77%)84.16%
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]