A Longitudinal Study on Oxaliplatin Induced Peripheral Neuropathy – Incidence and Facts About the “Real Life” Population And Actual Dose

INTRODUCTION: The real incidence of platinum drugs Chemotherapy Induced Peripheral Neuropathy (CIPN) is yet to be defined. Oxaliplatin (L-OHP) is associated with 2 different neurotoxicity: 1) acute neurotoxicity, (axonal hyperexicitability in days following iv administration with transient symptoms, such as cold-induced paresthesias); 2) chronic neuropathy, (sensory axonal one) which it is suggested to be developed in 10-20% of patients, with a threshold cumulative dose of 800-1000 mg/m2. Here an ongoing study is reported, aimed to better clarify incidence and issue in assessment, taking into account the actual L-OHP dose received by patients. METHODS: Patients eligible to undergo L-OHP based chemotherapy (FOLFOX-4) for colorectal cancer, are being enrolled. Subjects undergo a formal neurological examination, using the clinical version of the Total Neuropathy Score (TNSc), before starting CT (T0), after 6 cycles (T1) and at the end of treatment (T2); a neurophysiological assessment of limb distal nerves is also performed every time and acute toxicity phenomena record is made thorough a specifically designed questionnaire. RESULTS: Here data on 36 consecutive patients are shown. Median age was 62 (42-83); 67% of patients were male. 75% of patients were treated in an adjuvant setting. 6 patients were lost at T1 and 4 at T2, due to L-OHP discontinuation (mainly for hematological toxicities). The actual median cumulative dose was 839,5 (375,7-1021) mg/m2 and actual median dose intensity was 31,02 (14,45-42,50) mg/m2/week. At T0: median TNSc score was 0 (0-5); 17% of patients showed neurophysiological alterations. At T1: median TNSc score was 1 (0-6), 20% of patients showed alterations at neurophysiological assessment; 100% of patients showed at least one acute toxicity symptom. At T2: median score for TNSc was 4,5 (0-11), 73 % of patients showed alterations at neurophysiological assessment; 100% of patients showed at least one acute toxicity symptom. DISCUSSION: The novelty of the study is the accurate neurological assessment (TNSc, neurophysiology, acute symptoms questionnaire), with a concomitant registration of the actual, and not only the planned, doses of L-OHP received by each patient. As expected (but not recorded in the vast majority of the reported studies) the real life population received less than the planned dose (here, 80% of planned cumulative dose and 70% of planned dose intensity). This observation strongly supports the fact that L-OHP threshold dose for CIPN might have been underestimated so far and it suggests the need for a revision of the available data in order to analyse them more reliably.