Oxaliplatin-Induced Peripheral Neuropathy and Identification of Unique Severity Groups in Colorectal Cancer

Abstract

Context Oxaliplatin-induced peripheral neuropathy (OIPN) is a dose limiting toxicity of oxaliplatin and affects most colorectal cancer (CRC) patients. OIPN is commonly evaluated by patient symptom report, using scales to reflect impairment. They do not discriminate between unique grouping of symptoms and signs, which impedes prompt identification of OIPN. Objective Our study objective was to identify clusters of symptoms and signs that differentiated underlying clinical severity and segregated patients within our population into OIPN subgroups. Methods Chemotherapy naïve CRC patients (N=148) receiving oxaliplatin were administered the Total Neuropathy Score clinical (TNSc©), which includes symptom report (sensory, motor, autonomic) and sensory examination (pin sense, vibration, reflexes). The TNSc© was administered prior to chemotherapy initiation (T0), and following cumulative doses of oxaliplatin 510-520 mg/m2 (T1) and 1020-1040 mg/m2 of oxaliplain (T2). Using mean T2 TNSc© scores, latent class analysis (LCA) grouped patients into OIPN severity cohorts. Results LCA categorized patients into 4 distinct OIPN groups: low symptoms and low signs (N=54); low symptoms and intermediate signs (n=44); low symptoms and high signs (n=21); and high symptoms and high signs (n=29). No differences were noted among OIPN groups on age, sex, chemotherapy regimen, or cumulative oxaliplatin dose. Conclusion We identified OIPN patient groups with distinct symptoms/signs, demonstrating variability of OIPN presentation regardless of cumulative oxaliplatin dose. Over half of the sample had positive findings on OIPN examination despite little or no symptoms. Sensory examination of all patients receiving oxaliplatin is indicated for timely identification of OIPN, which will allow earlier symptom management.

Oxaliplatin, neurotoxicity, and the search for the lost channel

“…It is well-recognized that symptoms-based assessment is characterized by a wide variability and does not correspond to electrophysiological evaluation. 3 As a consequence, it is difficult to believe our study and the present study 1 are comparable.…”

Platinum‐induced peripheral neurotoxicity: From pathogenesis to treatment

“…Motor and autonomic symptoms and signs are uncommon in patients treated with platinum‐based compounds, but may be observed in severe cases . Therefore, when motor and autonomic symptoms are predominant and/or there is an absence of sensory involvement, an alternative diagnosis should be considered.…”

Systemic Evaluation on the Pharmacokinetics of Platinum-Based Anticancer Drugs From Animal to Cell Level: Based on Total Platinum and Intact Drugs

“…Preferably, oxaliplatin exhibits the best therapeutic effect on colon cancer (Rabik and Eileen, 2007;Chen and Lin et al, 2017;Lee et al, 2018). At the same time, in terms of toxicity, the main side effect of cisplatin is nephrotoxicity; bone marrow toxicity is more serious for carboplatin; and oxaliplatin mainly manifests as peripheral neurotoxicity (Knox et al, 1986;Chovanec et al, 2017;Griffith et al, 2017;Marmiroli et al, 2017;Milic et al, 2019). However, the pharmacology and toxicology of these platinum-based anticancer drugs have not been fully elucidated yet (Hanada et al, 2008).…”