Peripheral neuropathies induced by cancer chemotherapy (CIPN) remain a problem in oncology.
These CIPN are induced by certain classes of chemotherapy such as taxanes (paclitaxel and
docetaxel), platinum salts (cisplatin and oxaliplatin), alkaloids of the Madagascar
periwinkle (vincristine), bortezomib, thalidomide and eribulin. These CIPN is essentially
resulting in sensory disturbances such as paresthesia, dysesthesia or numbness.
Unfortunately, no treatment can be offered as "gold standard" for preventing or treating the
CIPN. Therefore, oncologists reduce or stop doses of chemotherapy because patients suffering
from CIPN have a marked deterioration in their quality of life and suffer from comorbidities
such as anxiety, depression and sleep disorders.
Among chemotherapy, bortezomib remains relatively understudied in terms of pathophysiology,
compared to the platinum salts or taxanes, whereas the neurotoxicity of bortezomib remains a
limiting factor for treatment. Currently, bortezomib is indicated for the treatment in 1st
line of multiple myeloma in the following protocols:
Patients <65 years: Protocol VTD: Velcade (bortezomib), thalidomide, dexamethasone +
autologous transplant
Patients> 65: Protocol MPV: Melphalan, Prednisone, Velcade. Or Protocol VD: Velcade,
dexamethasone Since 2012, the FDA and the EMA have validated the subcutaneous
administration of bortezomib instead of intravenously, in order to limit the adverse
effects of bortezomib, including neurotoxicity. Indeed, a large study reported that the
subcutaneous bortezomib allowed to keep the same therapeutic efficacy while improving
the safety profile and in particular by limiting peripheral neuropathies (CIPN any
grade: 38% vs 53%, grade ≥2: 24% vs 41%, grade ≥3 6% vs 16%). However, a recent
retrospective study reported that the prevalence of peripheral neuropathies induced by
bortezomib after subcutaneous administration remain relatively high: CIPN any grade:
41%, grade ≥2: 18% grade ≥3: 4 %, and especially that this prevalence of CIPN is no
different between subcutaneous and intravenous route.
Bortezomib is administered subcutaneously to limit the appearance of neuropathic disorders
and no study has evaluated quantitatively and qualitatively (QST) the sensory disorders in
patients with peripheral neuropathies induced by bortezomib after subcutaneous
administration. On the other hand, a measurement tool like the QLQ-CIPN20 questionnaire
(EORTC) evaluating the intensity of sensory, motor and autonomic disorders associated with
CIPN has never been tested in this patient population. While the questionnaire is presented
as the most appropriate tool in the evaluation of CIPN.
Thus, the exploration of peripheral neuropathies induced by bortezomib after subcutaneous
administration through QST (thermal) and QLQ-CIPN20 questionnaire would complement the
clinical knowledge of the CIPN. This knowledge will be essential to propose and test new
strategies for treatment and prevention of peripheral neuropathies induced by bortezomib.
The objective of this study is twofold: (i) psychophysical evaluation of neuropathic
disorders by studying the QST (thermal and vibratory sensory thresholds, thermal nociceptive
thresholds) and (ii) quantitative and qualitative assessment of neuropathic disorders by the
QLQ -CIPN20 questionnaire (EORTC) and associated comorbidities in patients treated with
bortezomib (subcutaneous administration).
