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Neurological Adverse Effects in Patients of Advanced Colorectal Carcinoma Treated with Different Schedules of FOLFOX

DOI: 10.1155/2013/379870

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Abstract:

The study is designed to assess the frequency and severity of few dose limiting neurological adverse effects of four different schedules of FOLFOX. Patients with histologically confirmed advanced colorectal carcinoma (CRC) were included in the study. Toxicity was graded according to CTC v 2.0. The frequency of grade 3 and 4 adverse effects was comparatively assessed in each treatment arm. The difference in the pattern of toxicity between the treatment schedule was evaluated. The most frequent adverse symptom of neurological adverse effect was grade 1 paresthesia in the patients treated with FOLFOX4 schedule. Grade 4 peripheral neuropathy was reported in few patients of FOLFOX7 treatment arm. Frequency and onset of neurological adverse effects like paresthesia, dizziness, and hypoesthesia were significantly different ( ), whereas frequency and onset of peripheral neuropathy were highly significant ( ) in each treatment arm of FOLFOX. Peripheral neuropathy was associated with electrolyte imbalance and diabetes in few patients. Frequency of symptoms, for example, paresthesia, is associated with increased number of recurrent exposure to oxaliplatin (increased number of cycles) even at low doses (85?mg/m2), whereas severity of symptoms, for example, peripheral neuropathy, is associated with higher dose (130?mg/m2) after few treatment cycles. 1. Introduction Incorporation of Oxaliplatin in 5FU/LV regimen has increased the median overall survival rate and progression free survival in patients of advanced colorectal carcinoma. The most frequent dose limiting toxicity of Oxaliplatin is peripheral neuropathy next to neutropenia. Neurotoxicity of Oxaliplatin is exacerbated as an acute sensory transient response, for example, paresthesia and dysesthesia in hand, feet, and peri oral area [1], which appears during or after exposure to Oxaliplatin. Sensory neurotoxicity with oxaliplatin is progressive, cumulative, and reversible, often manifested as delayed effects (12 to 18 months after discontinuation of the therapy). Peripheral neuropathy is hence regarded as the main “safety concern” for chemotherapy with Oxaliplatin, evident as frequent distal, transient paresthesia within the first few minutes of infusion [2]. The cumulative peripheral sensory neuropathy at the total dose of 800?mg/m2 requires cessation of therapy [3]. Acute syndrome of neurotoxicity is evident in 1-2% of patients shortly after the infusion, whereas the chronic syndrome is manifested as a dose limiting toxicity in 12–15% patients at the cumulative dose of 780–850?mg/m2 [4]. The platinum

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