Neurological adverse events of mitotane in adrenocortical carcinoma: results of a pilot study.

Introduction: Mitotane, the only drug approved by the Food and Drug Administration (FDA) for the treatment of adrenocortical carcinoma, is associated with several side effects including neurotoxicity. The aim of our study is to investigate the relationship between mitotane plasma levels and neurological toxicity. Methods: We have considered five patients affected by adrenocortical carcinoma treated with mitotane. The neurological assessment included a neurological examination, an electroencephalogram, event-related potentials (P300), and a neuropsychological assessment. All of the patients were first considered at the onset of symptoms of neurotoxicity or when mitotanemia levels were above 18 mg/L, for the second time at mitotanemia normalization and subsequently at its further increase, or in case of persistent neurological abnormalities, some months after normalization. Results: At the first neurotoxicity, four patients showed impaired neurological examination, electroencephalogram, and P300; three patients had impaired neuropsychological assessment; one patient, only P300. At mitotanemia normalization, the neurological examination became normal in all patients and electroencephalogram normalized in one patient, improved in another one, continuing to be altered in the other three. P300 latency and neuropsychological assessment normalized in two patients and persisted altered in the patient experiencing long-term mitotane toxicity. At the third evaluation, in the patient with prolonged mitotane toxicity, the normal mitotanemia in the previous 9 months restored P300 and improved the electroencephalogram but not the neuropsychological assessment. In the two patients experiencing a further rise of mitotanemia, neurological examination was normal but P300 and electroencephalogram were altered. Conclusion: The results of our study highlighted the presence of neurophysiological and neuropsychological abnormalities associated with mitotane values above 18 mg/L.

Prevention of Bortezomib-Induced Peripheral Neuropathy in Newly Multiple Myeloma Patients Using Nervonic Acid, Curcuma Rizoma, and L-Arginine Compound: A Pilot Study.

INTRODUCTION: This is a phase II pilot study to evaluate the efficacy of a nutraceutical compound composed of nervonic acid, curcuma rizoma, and l-Arginine to prevent the onset of bortezomib-induced peripheral neuropathy (BIPN) in 16 newly diagnosed multiple myeloma (MM) patients treated with bortezomib (BTZ) over 6 months. MATERIALS AND METHODS: Assessments included neurological examination and electroneurography, Common Terminology Criteria for Adverse Events (NCI-CTCAE), reduced version of Total Neuropathic Score (TNSr), pain evaluation, functional autonomy scales, self-perceived symptoms and quality of life questionnaires at baseline and after 6 months. RESULTS: No patients were symptomatic at baseline, despite neurophysiological data and TNSr evidence of peripheral neuropathy (PN) in 11 of them. After 6 months, only 9 patients completed the study. All had modifications in neurological examination with 8 out of 9 showing neurophysiological data of PN (2 of which had a NCI-CTCAE grade of neurotoxicity ≥2); 4 patients dropped out due to BIPN, 2 because of MM progression, 1 for scarce compliance. DISCUSSION: In our study, the compound was not adequate to prevent BIPN. The incidence of subclinical PN in MM patients is a risk factor for the development of severe neurotoxicity during BTZ treatment. For this reason to evaluate the efficacy of any preventive compound, as well as to manage MM patients, it should be mandatory to include neurophysiological study as a standard procedure.

Peripheral neurotoxicity of weekly paclitaxel chemotherapy: a schedule or a dose issue?

PURPOSE: The rationale for intensification strategies is that more frequent exposure to chemotherapeutics could enhance antitumor activity. Several trials investigated weekly paclitaxel administration, but there are no clear data concerning peripheral neurotoxicity. The aim of this study was to assess the incidence of peripheral neurotoxicity in patients affected by advanced breast cancer treated with weekly paclitaxel. PATIENTS AND METHODS: Neurotoxicity was assessed with neurologic and neurophysiologic evaluation before treatment and after 12 weeks and 24 weeks. A total neurotoxicity score was assigned to each patient on the basis of neurophysiologic and neuropathic signs and symptom changes. Seventeen patients entered the study. RESULTS: After 12 weeks of treatment, 71% showed moderate clinical and/or neurophysiologic signs of neurotoxicity; after 24 weeks, the incidence of neurotoxicity increased to 96%. Sural amplitude at the 24-weeks examination significantly decreased from basal mean value (13.5 microv, standard deviation [SD] 6 microv vs. 7 microv, SD 5.9 microv, respectively; P = 0.01), whereas median sensory amplitude decreased after 24 weeks from 10.3 microv, SD 6.2 microv to 4.9 microv, SD 3.8 microv (P = 0.001). In a subset of 11 patients, we obtained a follow-up examination after 6 months from the end of treatment. In all patients, examined signs and symptoms of neurotoxicity improved with recovery of subjective neuropathic symptoms and neurophysiologic findings. CONCLUSION: Our results demonstrate, in a little population of patients evaluated with a comprehensive neurologic assessment, that weekly paclitaxel is related to a very high incidence of peripheral neurotoxicity. Follow-up data obtained in a subset of patients indicate that peripheral neurotoxicity is reversible.