Dysphonia induced by anti-angiogenic compounds

Abstract

The number of studies reporting the benefit of angiogenesis inhibition is steadily increasing. Anti-angiogenic drugs, used as monotherapy or in association with chemotherapy, have been shown to benefit patients with several different malignancies. Despite the benefits of these therapies, however, each drug has different side effects. This review is specifically focused on analyzing the frequency of one of the complications the most frequently overlooked by physicians, dysphonia. Perhaps this side effect is overlooked because it is not life-threatening, but dysphonia may nevertheless affect quality of life considerably. We reviewed 88 studies concerning treatment with anti-angiogenics (bevacizumab, aflibercept, sunitinib, sorafenib, pazopanib, axitinib and regorafenib) presently approved for clinical use, to review the incidence of dysphonia or voice changes in phase I, II and III closed clinical studies reported in ClinicalTrials.gov until March 2013. We found that almost all studies reported certain degree of dysphonia in the trial arms associated with anti-angiogenic treatment. We discuss these findings in light of the fact that it is not an uncommon side effect in patients exposed to these kinds of drugs. Particularly for treatments with axitinib, aflibercept and regorafenib, the angiogenesis inhibition possibly plays a role by altering the larynx in some way and modifying vocal fold vibrations, leading to dysphonia.

A large-scale prospective registration study of the safety and efficacy of sorafenib tosylate in unresectable or metastatic renal cell carcinoma in Japan: results of over 3200 consecutive cases in post-marketing all-patient surveillance

“…This survey including these exploratory landmark analyses showed an association between longer survival (OS and PFS) and an early onset of specific ADRs. Among them, hypertension and dysphonia have been commonly reported in patients treated with VEGF signaling-pathway inhibitors ( 37 , 38 ). The correlation between hypertension and longer OS/PFS was shown for sorafenib and axitinib in the AXIS trial ( 39 ), and in a retrospective analysis of four clinical trials of sunitinib ( 40 ).…”

A case of effective disease control of advanced gastric cancer following ramucirumab plus FOLFIRI in second line treatment in clinical practice

“…В представленном клиническом случае продемонстрировано развитие такого редкого нежелательного явления, как повреждение голосовых связок. Ранее это явления описывалось при применении различных ингибиторов ангиогенеза, таких как бевацизумаб, афлибирцепт, сунитиниб, сорафениб, пазопаниб, акситиниб и регорафениб [27]. Причиной такой клинической картины является регрессия капилляров слизистой оболочки верхних дыхательных путей на фоне терапии антиангиогенными препаратами [28].…”

Aflibercept: side effects in focus

“…Причина данного типа осложнения пока точно не известна, возможно, в основе токсичности лежит снижение васкуляризации и гидратации слизистой оболочки, выстилающей голосовые складки, что приводит к их ригидности [23]. Данный тип осложнений проходит после отмены препарата, однако сама по себе дисфония не может являться причиной отмены или редукции доз афлиберцепта [19].…”