Prevalence, Intensity and Consequences of Bortezomib-induced Neuropathic Disorders.

Cancer-induced peripheral neuropathies (CIPN) remain a real problem in oncology (Balayssac et al., 2011). These CIPN are induced by certain classes of anticancer drugs such as taxanes (paclitaxel and docetaxel), platinum salts (cisplatin and oxaliplatin), alkaloids of Madagascar periwinkle (vincristine), bortezomib, thalidomide and eribulin (Balayssac et al., 2011; Vahdat et al., 2013). These CIPN essentially translate into sensory disorders such as paresthesia, dysesthetics or numbness. More rarely, these CIPN may be associated with motor or vegetative disorders (Balayssac et al., 2011). According to the recent meta-analysis by Hershman et al., no treatment can be proposed as a "gold standard" for preventing or treating CIPN (Hershman et al., 2014). As a result, oncologists reduce or stop doses of neurotoxic anticancer drugs because patients with CIPN have a marked deterioration in quality of life and co-morbidities such as anxiety, depression and sleep disorders (Hong et al., 2014; Mols et al., 2014). Therefore, understanding the pathophysiology of CIPN is essential to propose new therapeutic strategies. Among neurotoxic anticancer drugs, bortezomib remains relatively little studied in terms of pathophysiology compared to platinum salts or taxanes, while the neurotoxicity of bortezomib remains a limiting factor in treatment. Since 2012, the FDA and EMA have validated the administration of bortezomib subcutaneously instead of intravenously in order to limit the neurotoxicity of bortezomib (Minarik et al., 2015). Indeed, a large study (N=222) reported that subcutaneous administration of bortezomib allowed the same therapeutic efficacy to be maintained while improving the safety profile and in particular limiting peripheral neuropathies (CIPN all grades: 38% vs. 53%, p=0.044, grade\> 2: 24% vs. 41%, p=0.012 and grade\> 3: 6% vs. 16%, p=0.026) However, a recent retrospective study (N=446) reports that the prevalence of bortezomib-induced peripheral neuropathies after subcutaneous administration remains relatively high: all grade: 41%, grade\> 2: 18%, grade\> 3: 4%, and above all that this prevalence is not different between subcutaneous and intravenous routes (Minarik et al., 2015).