Aspects of vincristine-induced neuropathy in hematologic malignancies: a systematic review

Abstract

Purpose Vincristine is widely used as anticancer therapy for a variety of hematological malignancies. The treatment is limited by progressive vincristine-induced neuropathy, possibly including both peripheral sensory and motor nerves, autonomic nervous functions, and the central nervous system. This dose-limiting side-effect can diminish quality of life and, furthermore, cause discontinuation of vincristine treatment. The present review elucidates the current knowledge regarding vincristine-induced neuropathy in hematologic malignancies, focusing on neuropathy assessment, clinical and molecular predictive markers, drug–drug interference, prevention, and treatment. Methods This review is conducted by a systematic search strategy for the identification of relevant literature in the PubMed and Embase databases. Results No clinical parameters displayed convincing potential as predictors of vincristine-induced neuropathy; however, preexisting neuropathy was consistently reported to be associated with an increased risk of neurotoxicity. In contrast, molecular markers, including polymorphisms in genes involved in the pharmacodynamics and pharmacokinetics of vincristine, displayed great potential as predictive markers of neuropathy incidence and severity. Furthermore, antifungal drugs, such as itraconazole and voriconazole, decrease the metabolism of vincristine and consequently lead to severe neuropathy when co-administered with vincristine, underscoring why fluconazole should be the antifungal drug of choice. Conclusion Reports from the 71 included studies clearly emphasize the lack of consistency in neuropathy assessment, grading systems, and reporting, making it difficult to interpret results between studies. Thus, truer clinical and molecular markers could emerge if the consistency of neuropathy detection and reporting increases by the use of conventional standardized neuropathy assessment tools and grading scales. Electronic supplementary material The online version of this article (10.1007/s00280-019-03884-5) contains supplementary material, which is available to authorized users.

MicroRNAs associated to single drug components of R-CHOP identifies diffuse large B-cell lymphoma patients with poor outcome and adds prognostic value to the international prognostic index

“…Evaluation of prognostic impact in this study is based on retrospective clinical cohorts where treatment conditions are not strictly unified regarding number of cycles, dosing [19,20] and individual dose reductions due to side-effects like neuropathy [36]. Taking this and the pharmacological information on no synergistic effect of R-CHOP into account [8], single drug screens were used rather than combinational assays to identify candidate miRNAs to be assessed in non-weighted models using either multivariate Cox regression or random survival forest models.…”

Vocal cord paralysis secondary to vincristine treatment in children -- A case series of seven children and literature review

“…None of the patients were on any medications such as azole antifungals that are known to increase the toxicity of vincristine including vcp 6,7 .…”

“…Similarly in the other cases that were identified symptoms resolved after cessation of vincristine which had variable rates of recovery from weeks to months. It is known that drugs such as itraconazole, ,erythromycin, isoniazid, phenytoin and mitomycin c may increase the toxicity of vincristine thus making neurotoxicity more likely 5,7 . Further to this, hepatic impairment may also contribute as vincristine is metabolised by the cytochrome p450 enzymes.…”

Inflammation and Impact of Vincristine and Enterosorption Use in Chemically Induced Colon Carcer in Rats

“…Vincristine is a herbal cytostatic, it is an important component of the combined treatment regimen for malignant neoplasms. However, in the present literature there are some publications on the use of periwinkle alkaloids in the chemotherapeutic treatment of colorectal cancer [6].…”