Vinflunine: clinical perspectives of an emerging anticancer agent

Yip, Adrian Y S; Ong, Eleanor Yuen-Yuen; Chow, Louis W C

doi:10.1517/13543784.17.4.583

Cited by 27 publications

(7 citation statements)

References 46 publications

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“…Vincristine, vinblastine, and vindesine are the irst vinca alkaloids used as antitumor drugs. Vinorelbine is the irst new second-generation vinca alkaloid, while vinlunine, a bis-luorinated vinorelbine derivative, was synthesized by superacid chemistry and studied in phase I-III clinical trials [14,15].…”

Section: Microtubule-destabilizing Agentsmentioning

confidence: 99%

Targeting the Cytoskeleton with Plant-Bioactive Compounds in Cancer Therapy

Ardelean¹

2017

Cytoskeleton - Structure, Dynamics, Function and Disease

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In this overview we describe the main plant-derived bioactive compounds used in cancer therapy which has the cell cytoskeleton as therapeutic target. Three major classes of these compounds are described: antimitotics with microtubule-destabilizing and-stabilizing efects, plant-bioactive compounds that interact with intermediate ilaments/actin, and plant-bioactive compounds that interact with intermediate ilaments like keratins and vimentin. We also focus on the molecular aspects of interactions with their cellular targets: microtubules, intermediate ilaments, and microilaments. Some critical aspects of cardiac side efects of cancer chemotherapy are also discussed, focusing on cardiac cytoskeleton and protective efect of plant-derived compounds. The application of plant bioactives in the treatment of cancer has resulted in increased therapeutic eicacy through targeting the cytoskeleton, respectively, prevention of the injury of cytoskeletal components elicited by chemotherapeutics.

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Section: Microtubule-destabilizing Agentsmentioning

confidence: 99%

Targeting the Cytoskeleton with Plant-Bioactive Compounds in Cancer Therapy

Ardelean¹

2017

Cytoskeleton - Structure, Dynamics, Function and Disease

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“…Vindesine is undergoing clinical trials, primarily for treatment of acute lymphocytic leukemia 13. Vinfluine, the newest member of the vinca alkaloid family, has shown better efficacy than vinblastine in a variety of tumors and is currently in clinical trials to test for activity against solid tumors 15. The dose limiting toxicities of this class of drugs also varies with structure; neurotoxicity is the common dose-limiting toxicity associated with vincristine treatment, while neutropenia is often the most serious side effect of treatment with the other vinca alkaloids.…”

Section: Microtubule Destabilizersmentioning

confidence: 99%

Microtubule dynamics as a target in oncology

Risinger

Giles

Mooberry

2009

Cancer Treatment Reviews

227

197

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Drugs that affect microtubule dynamics, including the taxanes and vinca alkaloids, have been a mainstay in the treatment of leukemias and solid tumors for decades. New, more effective microtubule-targeting agents continue to enter into clinical trials and some, including the epothilone ixapebilone, have been approved for use. In contrast, several other drugs of this class with promising preclinical data were later shown to be ineffective or intolerable in animal models or clinical trials. In this review we discuss the molecular mechanisms as well as preclinical and clinical results for a variety of microtubule-targeting agents in various stages of development. We also offer a frank discussion of which microtubule-targeting agents are amenable to further development based on their availability, efficacy and toxic profile.

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“…Due to an excessive rate of hematologic toxicity in early phase II trials, doses in the phase II and III studies were 320 mg/m 2 every 21 days [4]. Common grade 3/4 adverse effects of vinflunine include neutropenia, constipation, and fatigue [2].…”

Section: Introductionmentioning

confidence: 99%

A phase I evaluation of the combination of vinflunine and erlotinib in patients with refractory solid tumors

et al. 2010

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SummaryPurpose-Epidermal growth factor receptor (EGFR) inhibition may overcome chemotherapy resistance by inhibiting important anti-apoptotic signals that are constitutively activated by an overstimulated EGFR pathway.Methods-This phase I dose escalation trial assessed the safety and efficacy of vinflunine, a novel vinca alkaloid microtubule inhibitor, with erlotinib, an EGFR tyrosine kinase inhibitor, in patients with refractory solid tumors.Results-Seventeen patients were treated, 10 with continuous erlotinib, and 7 with intermittent erlotinib. At dose level 1, vinflunine 280 mg/m 2 IV day 1 and erlotinib 75 mg PO days 2-21 ("continuous erlotinib") in 21 day cycles, two of four patients experienced DLTs. At dose level -1 (vinflunine 250 mg/m 2 every 21 days and erlotinib 75 mg/day), two of six patients experienced DLTs. The study was amended to enroll to "intermittent erlotinib" dosing: vinflunine day 1 and erlotinib days 2-15 of a 21 day cycle. Two of seven experienced DLTs and the study was terminated. One patient with breast cancer had a partial response; three had stable disease ≥6 cycles. All were treated in the continuous erlotinib group.Conclusions-Given the marked toxicity in our patient population, the combination of vinflunine and erlotinib cannot be recommended for further study with these dosing schemas.

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Vinflunine: clinical perspectives of an emerging anticancer agent

Cited by 27 publications

References 46 publications

Targeting the Cytoskeleton with Plant-Bioactive Compounds in Cancer Therapy

Targeting the Cytoskeleton with Plant-Bioactive Compounds in Cancer Therapy

Microtubule dynamics as a target in oncology

A phase I evaluation of the combination of vinflunine and erlotinib in patients with refractory solid tumors

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