Multicenter randomized controlled trial to evaluate the efficacy and tolerability of frozen gloves for the prevention of chemotherapy-induced peripheral neuropathy.

BACKGROUND: This study investigated the efficacy and tolerability of wearing frozen gloves (FGs) during chemotherapy to prevent chemotherapy-induced peripheral neuropathy (CIPN) as reported by patients and influence on quality of life (QoL). PATIENTS AND METHODS: Cancer patients starting treatment with oxaliplatin, docetaxel or paclitaxel between February 2013 and May 2016 at the medical oncology department were eligible. Patients were randomized into groups wearing FGs on both hands during treatment and those not wearing FGs during treatment. Self-reported CIPN and QoL were measured with the European Organisation for the Research and Treatment of Cancer Quality of Life (EORTC QLQ) CIPN20 and QLQ-C30 at four time points: baseline (t0), after three cycles (t1), end of chemotherapy (t2) and after 6 months (t3). RESULTS: The study included 180 patients with 90 patients in both arms. They mostly underwent treatment of colorectal or breast cancer. Thirty-one patients (34%) discontinued FGs, mainly due to discomfort. Intention-to-treat analyses showed no important differences in reported EORTC QLQ CIPN20 subscales between the FG group and control group; however, the analyses showed the patients experienced reduced tingling in fingers/hands [ß = -10.20, 95% confidence interval (CI) = -3.94 to -3.14, P = 0.005] and less trouble opening a jar or bottle due to loss of strength in hands (ß = -6.97, 95% CI = -13.53 to -0.40, P = 0.04) in the FG group compared with the control group. Per-protocol analyses showed similar results: reduced aching or burning pain in fingers/hands (ß = -4.37, 95% CI = -7.90 to -0.83, P = 0.02) and cramps in hands (ß = -3.76, 95% CI = -7.38 to -0.14, P = 0.04). Differences in tingling in fingers/hands at t1 were clinically relevant. In addition, those treated with FGs reported overall better QoL (ß = 4.79, 95% CI = 0.37 to 9.22, P = 0.03) and physical functioning (ß = 5.66, 95% CI = 1.59 to 9.73, P = 0.007) than the control. No difference in dose reductions was observed. CONCLUSIONS: No difference in CIPN subscales was reported between intervention arms. Wearing FGs might reduce some neuropathy symptoms in the hands, potentially resulting in a better QoL; however, one-third of the FG group discontinued the study before the end of treatment. Future studies should focus on the method of limb hypothermia to prevent CIPN. TRIAL REGISTRATION NUMBER: NL39650.015.12.

Chemotherapy-induced neuropathy in multiple myeloma: influence on quality of life and development of a questionnaire to compose common toxicity criteria grading for use in daily clinical practice.

PURPOSE: Chemotherapy-induced peripheral neuropathy (CIPN) may negatively influence multiple myeloma (MM) patients' health-related quality of life (HRQOL). Dose modification is the only way to minimize CIPN. To measure CIPN in daily practice, the Indication for Common Toxicity Criteria (CTC) Grading of Peripheral Neuropathy Questionnaire (ICPNQ) was developed which can be completed within five minutes by the patient. The aims of this study were to (1) perform a psychometric evaluation of the ICPNQ and (2) examine the prevalence of CIPN and its influence on HRQOL in population-based MM patients. METHODS: One hundred fifty-six MM patients, diagnosed between 2000 and 2014, completed the ICPNQ, European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Chemotherapy-Induced Peripheral Neuropathy 20 (EORTC QLQ-CIPN20), and EORTC QLQ-C30 (65 % response). RESULTS: The psychometric analyses showed a Cronbach's alpha of 0.84, 0.74, and 0.61 for, respectively, the sensory, motoric, and autonomic subscales of the ICPNQ. Test-retest reliability and construct validity were good for all subscales. Overall, 65 % of patients reported grade 2-3 neuropathy according to the ICPNQ. Patients with the highest CTC grades (grade 2 with neuropathic pain and grade 3 (38 %)) according to the ICPNQ reported significantly worse scores on all EORTC QLQ-CIPN20 subscales compared to patients with lower CTC grades (p ≤ 0.002). In addition, they reported statistically significant and clinically relevant worse HRQOL scores on almost all EORTC QLQ-C30 subscales. CONCLUSIONS: CIPN is a common side effect in MM patients, which has a negative impact on HRQOL. The ICPNQ is a valid instrument to distinguish the highest CIPN CTC grades from the lower CTC grades necessary to decide on dose modifications of chemotherapy in daily clinical practice.

A systematic review on chronic oxaliplatin-induced peripheral neuropathy and the relation with oxaliplatin administration.

PURPOSE: The aim of this study was to systematically review the literature on the influence of oxaliplatin administration (e.g. cumulative dose, dose intensity, number of cycles and combination regimen) on the long-term prevalence of oxaliplatin-induced peripheral neuropathy (O-IPN) at least 12 months after termination of chemotherapy. METHODS: A computerized search of literature on databases PubMed and Cochrane was performed. Published original articles were included if they reported about long-term O-IPN and gave concomitant information about oxaliplatin therapy given to the patients. All articles were assessed for quality. RESULTS: We included 14 articles (n=3,869 patients), and the majority of these studies were of high quality. All included patients who were treated for colorectal cancer, mainly with oxaliplatin in combination with 5-fluorouracil/leucovorin. Median cumulative doses and dose intensity varied between 676 and 1,449 mg/m2 and 30.8 and 42.6 mg/m2/week, respectively. Neuropathy assessment differed between studies, and the National Cancer Institute-Common Terminology Criteria (NCI-CTC) was used most often. The degree of neuropathy ranged from grade 0 to 3. Only six studies directly assessed the relationship between oxaliplatin administration and neuropathy. Of these studies, five did find a relation between neuropathy and higher cumulative dose, while one study did not find a relation. CONCLUSIONS: O-IPN is still present in a great amount of patients in ≥12 months after termination of therapy. A higher cumulative dose is likely to have an influence on the development of long-term O-IPN. More studies are needed that assess long-term neuropathy and oxaliplatin administration by means of validated neuropathy assessments.

Chemotherapy-induced neurotoxicity: the value of neuroprotective strategies.

Chemotherapy-induced peripheral neuropathy (CIPN) is a common major dose-limiting side effect of many chemotherapeutic agents, including platinum compounds, taxanes, vinca alkaloids, thalidomide and newer agents such as bortezomib. The incidence and degree of neuropathy depends on the type of cytotoxic drug, the duration of administration, cumulative dose and pre-existing peripheral neuropathy. Because of increasing survival rates of patients treated with neurotoxic agents, CIPN is accompanied by a significant decrease in the patient's quality of life among cancer survivors. Therefore, several neuroprotective strategies, including calcium/magnesium infusion, amifostine, gluthatione, glutamine, acetyl-L-carnitine and erythropoietin as most promising, have been investigated to decrease the neurotoxicity without compromising anti-tumour efficacy. However, clinical evidence for the efficacy of these drugs is sparse. In this review we will give an outline of the neurotoxic effects of chemotherapeutic agents, their clinical manifestations and potential neuroprotective strategies.