Acute chemotherapy-induced peripheral neuropathy due to oxaliplatin administration without cold stimulation.

PURPOSE: The incidence and time of onset of acute chemotherapy-induced peripheral neuropathy (ACIPN) caused by oxaliplatin remain unclarified. Hence, we investigated the prevalence, onset time, and location of ACIPN symptoms in patients with colorectal cancer (CRC) receiving oxaliplatin without cold stimulation. METHODS: The study cohort comprised patients receiving oxaliplatin for CRC at our hospital between April 2017 and August 2018. Patients were instructed not to touch and/or drink cold things and were monitored for ACIPN symptoms in the hospital for 24 h after chemotherapy. ACIPN symptoms that appeared > 24 h after chemotherapy were recorded at the next visit. Symptom appearance time was defined as the duration from the administration of chemotherapy until the appearance of paresthesia classified as grade 1 using the Common Terminology Criteria for Adverse Events. RESULTS: Forty-five patients received chemotherapy, comprising 23 men and 22 women, aged 67 years (29-88 years). The location of ACIPN was the fingers in 55.6% of cases, pharynx in 26.7%, perioral region in 24.4%, and feet in 6.7%. The average duration from oxaliplatin administration to symptom development was 182 min (range 62-443 min) for the fingers, 291 min (176-432 min) for the pharynx, 311 min (127-494 min) for the perioral region, and 297 min (234-355 min) for the feet. Pharyngeal symptoms were more common in patients older than 65 years than in those younger than 65 years. CONCLUSIONS: The incidence and time of the onset of ACIPN caused by oxaliplatin varies between the body and regions.

The incidence of acute oxaliplatin-induced neuropathy and its impact on treatment in the first cycle: a systematic review.

BACKGROUND: Although acute oxaliplatin-induced neuropathy (OXIPN) is frequently regarded to be transient, recent studies have reported prolongation of infusion times, dose reduction and treatment cessation following the first dose of oxaliplatin in quarter of patients. Acute OXIPN is also a well-established risk factor for chronic neuropathy. However, there is underreporting of these parameters during the acute phase (≤ 14 days). This paper systematically reviews the incidence of acute OXIPN and its impact on treatment in the first cycle. METHODS: A systematic literature search was performed using PubMed and Medline. Published original articles were included if they described details about prevalence of oxaliplatin-induced acute neuropathy. RESULTS: Fourteen studies, comprised of 6211 patients were evaluated. The majority of patients were treated with oxaliplatin in combination with leucovorin and fluorouracil (FOLFOX). Most studies used the National Cancer Institute Common Toxicity Criteria to assess acute neuropathy. Acute neuropathy (Grades 1-4) was the most common event with prevalence ranging from 4-98%, followed by haematological (1.4-81%) and gastrointestinal (1.2-67%) toxicities, respectively. Drug regimens, starting dose of oxaliplatin and neuropathy assessment tools varied across studies. In addition, moderate to severe toxicities were common in patients that received a large dose of oxaliplatin (> 85 mg/m2) and/ or combined drugs. The majority of studies did not report the factors affecting acute neuropathy namely the range (minimal) doses required to evoke acute neuropathy, patient and clinical risk factors. In addition, there was no systematic reporting of the number of patients subjected to prolonged infusion, dose reduction, treatment delay and treatment cessation during the acute phase. CONCLUSION: Despite the heterogeneity of studies regarding oxaliplatin starting dose, drug regimen, neuropathy assessment tools and study design, a large number of patients developed acute neuropathy. To develop a better preventive and therapeutic guideline for acute/chronic neuropathy, a prospective study should be conducted in a large cohort of patients in relation to drug regimen, starting/ranges (minimal) of doses producing acute neuropathy, treatment compliance, patient and clinical risk factors using a standardised neuropathy assessment tool.

Hyperacute peripheral neuropathy is a predictor of oxaliplatin-induced persistent peripheral neuropathy.

PURPOSE: Chronic peripheral neuropathy is a major adverse response to oxaliplatin-containing chemotherapy regimens, but there are no established risk factors pertaining to it. We investigated the efficacy of hyperacute peripheral neuropathy (HAPN) as a predictor of oxaliplatin-induced persistent peripheral neuropathy (PPN). METHODS: Forty-seven cases of stage III colorectal cancer who received adjuvant chemotherapy with oxaliplatin after curative surgery between January 2010 and August 2014 were retrospectively reviewed. HAPN was defined as acute peripheral neuropathy (APN) occurring on day 1 (≤24 h after oxaliplatin infusion) of the first cycle. PPN was defined as neuropathy lasting >1 year after oxaliplatin discontinuation. RESULTS: The average total dose of oxaliplatin was 625.8 mg/m2, and the average relative dose intensity was 66.7%. Twenty-two of the 47 patients (46.8%) had PPN and 13 (27.7%) had HAPN. Male sex, treatment for neuropathy, HAPN, and APN were significantly more frequent in patients with PPN (p = 0.013, 0.02, <0.001, and 0.023, respectively). There was no significant difference in the total oxaliplatin dose between patients with and without PPN (p = 0.061). Multivariate analyses revealed total dose of oxaliplatin and HAPN as independent predictors of PPN [p = 0.015; odds ratio (OR) = 1.005, 95% confidence interval (CI), 1.001-1.009 and p = 0.001; OR = 75.307, 5.3-1070.123, respectively]. The total dose of oxaliplatin was relatively lower in patients with HAPN than that in those without HAPN in the PPN-positive group (not significant, p = 0.068). CONCLUSION: HAPN was found to be a predictor of oxaliplatin-induced PPN.

Recognition and Management of Neuromuscular Emergencies.

Acute neuromuscular disorders represent an important subset of neurologic consultation requests in the inpatient setting. Although most neuromuscular disorders are subacute to chronic, hospital-based neurologists encounter neuromuscular disorders presenting with rapidly progressive or severe weakness affecting limb movement, respiratory, and bulbar function. Recalling fundamentals of neurologic localization assists in prompt recognition and diagnosis. Despite the differing localizations and the causal diagnoses, the initial management principles of acute myopathies, neuropathies, and neuromuscular junction disorders are similar.

Effect of intact oxaliplatin in plasma on a cold allodynia after multiple administrations in colorectal cancer model rats.

BACKGROUND: Oxaliplatin (L-OHP)-induced acute neuropathy is a major factor for influencing treatment compliance in patients receiving chemotherapy for colorectal cancer (CRC). Acute neuropathy is caused by the intact L-OHP affecting the function of transient receptor potential vanilloid 1 (TRPV1) channel. In this study, the effectiveness of the detection of the intact L-OHP and the association with the severity of L-OHP-induced acute neuropathy were investigated using a rat model of CRC. METHODS: Wistar male rats were prepared as models of CRC by using 1,2-dimethylhydrazine (DMH) and dextran sulfate. Intravenous L-OHP was administered (weekly) to CRC rats for 4 weeks, at doses of 3, 5, or 8 mg/kg, respectively. Pharmacokinetic and tumor distribution profiles of animals with intact L-OHP were observed on days 1 and 22. Cold allodynia was determined as a read-out of acute neuropathy using the acetone test over the 4 weeks. RESULTS: The mean AUC0-∞ values for the intact L-OHP were increased dose-dependently at the three doses. The accumulation of intact L-OHP was confirmed following an increase in L-OHP concentration on day 22. Acute neuropathy was observed from day 2 at all doses and the withdrawal response correlated with AUC (R2 =0.9816). CONCLUSIONS: To prevent the onset of L-OHP-induced acute neuropathy, the timely detection of the intact L-OHP is important. These findings could be a basis of the establishment a pharmacokinetic and toxicodynamic model to aid the planning of therapy cycle completion for CRC.