Abstract
BackgroundPlatinum-based drugs, such as cisplatin and oxaliplatin, are well-known for inducing chronic sensory neuropathies but their acute and motor neurotoxicities are less well characterised. Use was made of nerve conduction studies and needle electromyography (EMG) to assess motor nerve excitability in cancer patients during their first treatment cycle with platinum-based chemotherapy in this study.MethodsTwenty-nine adult cancer patients had a neurophysiological assessment either before oxaliplatin plus capecitabine, on days 2 to 4 or 14 to 20 after oxaliplatin plus capecitabine, or on days 2 to 4 after carboplatin plus paclitaxel or cisplatin, undertaken by a neurophysiologist who was blinded to patient and treatment details. Patients completed a symptom questionnaire at the end of the treatment cycle.ResultsAbnormal spontaneous high frequency motor fibre action potentials were detected in 100% of patients (n = 6) and 72% of muscles (n = 22) on days 2 to 4 post-oxaliplatin, and in 25% of patients (n = 8) and 13% of muscles (n = 32) on days 14 to 20 post-oxaliplatin, but in none of the patients (n = 14) or muscles (n = 56) tested prior to oxaliplatin or on days 2 to 4 after carboplatin plus paclitaxel or cisplatin. Repetitive compound motor action potentials were less sensitive and less specific than spontaneous high frequency motor fibre action potentials for detection of acute oxaliplatin-induced motor nerve hyperexcitability but were present in 71% of patients (n = 7) and 32% of muscles (n = 32) on days 2 to 4 after oxaliplatin treatment. Acute neurotoxicity symptoms, most commonly cold-induced paraesthesiae and jaw or throat tightness, were reported by all patients treated with oxaliplatin (n = 22) and none of those treated with carboplatin plus paclitaxel or cisplatin (n = 6).ConclusionsAbnormal spontaneous high frequency motor fibre activity is a sensitive and specific endpoint of acute oxaliplatin-induced motor nerve hyperexcitability, detectable on EMG on days 2 to 4 post-treatment. Objective EMG assessment of motor nerve excitability could compliment patient-reported symptomatic endpoints of acute oxaliplatin-induced neurotoxicity in future studies.
Highlights
Platinum-based drugs, such as cisplatin and oxaliplatin, are well-known for inducing chronic sensory neuropathies but their acute and motor neurotoxicities are less well characterised
These neurophysiological abnormalities included repetitive compound motor action potentials (CMAPs) during nerve conduction studies after a single electrical stimulus following the main CMAP, and high frequency motor fibre action potentials on needle electromyography (EMG) that occurred spontaneously and upon needle insertion or voluntary muscle contraction
Few or no subsequent studies by other groups have independently confirmed the occurrence of repetitive CMAPs and/or abnormal motor fibre action potentials in patients treated with oxaliplatin or other chemotherapy drugs
Summary
Platinum-based drugs, such as cisplatin and oxaliplatin, are well-known for inducing chronic sensory neuropathies but their acute and motor neurotoxicities are less well characterised. In a previous study of cancer patients treated with oxaliplatin [5,6], striking neurophysiological abnormalities were demonstrated suggesting a state of acute peripheral nerve hyperexcitability due to altered axonal ion channel activity These neurophysiological abnormalities included repetitive compound motor action potentials (CMAPs) during nerve conduction studies after a single electrical stimulus following the main CMAP, and high frequency motor fibre action potentials on needle electromyography (EMG) that occurred spontaneously and upon needle insertion or voluntary muscle contraction. Since these original reports, few or no subsequent studies by other groups have independently confirmed the occurrence of repetitive CMAPs and/or abnormal motor fibre action potentials in patients treated with oxaliplatin or other chemotherapy drugs
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