Statistical identification of predictors for peripheral neuropathy associated with administration of bortezomib, taxanes, oxaliplatin or vincristine using ordered logistic regression analysis

Abstract

Chemotherapy-induced peripheral neuropathy (CIPN) is a major drug-induced adverse reaction that becomes a dose-limiting toxicity. However, effective strategies for preventing or treating CIPN are lacking. Accordingly, this study aimed to statistically identify predictors for CIPN. Retrospective analysis was carried out for 190 patients who had been treated with bortezomib (n=28), taxanes (paclitaxel or docetaxel; n=58), oxaliplatin (n=52) or vincristine (n=52) at our hospital between April 2005 and December 2008. The severity of CIPN was assessed at the time of chemotherapy completion, graded as grade 0-5 in accordance with the National Cancer Institute Common Terminology Criteria for Adverse Events v3.0. Multivariate ordered logistic regression analysis was used to investigate predictors for CIPN. Predictors for CIPN in patients that were administered bortezomib were no co-administration of dexamethasone [odds ratio (OR), 0.455; confidence interval (CI), 0.208-0.955; P=0.0376] and sex (male) (OR, 3.035; CI, 1.356-6.793; P=0.0069). For taxanes (paclitaxel or docetaxel), the predictor for CIPN was a large number of chemotherapy cycles (OR, 2.379; CI, 1.035-5.466; P=0.0412). For oxaliplatin, the predictors for CIPN were a large number of chemotherapy cycles (OR, 3.089; CI, 1.598-5.972; P=0.0008) and no co-administration of non-steroidal anti-inflammatory drugs (OR, 0.393; CI, 0.197-0.785; P=0.0082). For vincristine, predictors for CIPN were a large number of chemotherapy cycles (OR, 6.015; CI, 1.880-19.248; P=0.0025) and co-administration of an analgesic adjuvant (OR, 3.907; CI, 1.383-11.031; P=0.0101). In conclusion, our study indicates that CIPN will be alleviated by the co-administration of dexamethasone with bortezomib and non-steroidal anti-inflammatory drugs with oxaliplatin.

Chemotherapy-induced peripheral neuropathy: review for clinical practice

“…An experimental study with rats has shown by electronic microscopy, that there were no significant pathological changes in the morphology of myelin sheath of animals treated with cisplatin, bortezomib and paclitaxel, although there has been decreased nervous conduction velocity 12 . There are evidences that platinum derivatives and taxanes would induce blood vessels endothelial cells apoptosis, with consequent nervous fibers ischemia 13 . Among pathophysiological CIPN mechanisms, it is currently recognized the role of neuroimmune interaction, since the release of cytokines and chemokines able to trigger peripheral neural injury seems to be a primary mechanism for the development of the syndrome.…”

“…CIPN incidence and severity are directly related to dose, number of treatment cycles, previous or simultaneous administration of neurotoxic anticancer agents and the type of impaired nervous fiber 13,18 . For example, when cisplatin is used alone, the frequency of neuropathic symptoms is around 50%, while 90 to 100% of females receiving the association of cisplatin and paclitaxel for ovarian cancer may present such symptom.…”

Predictors of Chemotherapy-Induced Peripheral Neuropathy

“…Reducing the dosage of bortezomib and/or changing the treatment schedule are also reportedly effective in alleviating bortezomib-induced PN (Argyriou et al, 2008a). However, neither the number of chemotherapy cycles nor the diagnosis of DM predicted bortezomib-induced PN (Kanbayashi et al, 2010). Additionally, since the use of thalidomide is not covered by the health insurance system in Japan, few patients (1 of 28 patients treated with bortezomib) received thalidomide co-administration (Kanbayashi et al, 2010).…”

“…However, neither the number of chemotherapy cycles nor the diagnosis of DM predicted bortezomib-induced PN (Kanbayashi et al, 2010). Additionally, since the use of thalidomide is not covered by the health insurance system in Japan, few patients (1 of 28 patients treated with bortezomib) received thalidomide co-administration (Kanbayashi et al, 2010). Thus, we did not include thalidomide in our analysis.…”

“…However, effective strategies for preventing or treating CIPN are lacking. Accordingly, we conducted a retrospective study to identify significant predictors for CIPN which would contribute to improving QOL among chemotherapy patients (Kanbayashi et al, 2010). Patients had been administered bortezomib (n=28), taxanes (paclitaxel or docetaxel; n=58), oxaliplatin (n=52) or vincristine (n=52) Japanese herbs (Shakuyaku-Kanzo-To and Gosha-Jinki-Gan).…”