- Email: [email protected]
OnabotulinumtoxinA for treatment of refractory cancer pain
Abstracts Toxins 2011 / Toxicon 68 (2013) 60–123
OnabotulinumtoxinA for treatment of refractory cancer pain S. Mittal, D. Machado, B. Jabbari Department of Neurology, Yale University School of Medicine, New Haven, CT, USA E-mail address: [email protected] (S. Mittal).
Purpose of study: To report the relief from refractory focal post-radiation or post-surgical cancer pain after local treatment with onabotulinumtoxinA. Methods used: Seven patients with moderate to severe focal pain associated with cancer resection or radiation or both as measured by a visual analog scale (VAS score of greater than five) were treated with local injection of onabotulinumtoxinA into the affected region. Patients’ response to treatment was evaluated by the Patient Global Assessment (PGA) scale (satisfaction subset) and the change in VAS pain score. Pain relief was considered significant when there was a drop of at least two or more grades on the VAS and there was satisfaction with treatment as reported by the PGA. Results: All seven patients reported a significant improvement in pain (mean drop in VAS score of 4.8). They described their response on Patient Global Assessment (PGA) as satisfactory (two patients) or very satisfactory (five patients). Six of the seven patients had significant improvement in quality of life. None of them reported any side-effects from the treatment. Four patients had a longterm follow-up (more than a year) that demonstrated consistent improvement with repeated injections. Conclusions: Local injection of onabotulinumtoxinA can significantly reduce refractory focal post-resection and postradiation pain in cancer patients. This observation warrants further investigation in this important pain disorder. http://dx.doi.org/10.1016/j.toxicon.2012.07.154
Electrophysiological study for assessment of botulinum toxin type A2 compared with type A1 in healthy volunteers Y. Mukai a, b, c, Y. Shimatani a, T. Kohda b, T. Sakamoto c, S. Kozaki b, R. Kaji a a
School of Medicine, University of Tokushima Faculty of Medicine, Tokushima, Japan b Department of Veterinary Sciences, School of Life and Environmental Sciences, Osaka Prefecture University, Osaka, Japan c Department of Neurology, National Center Hospital of Neurology and Psychiatry, Tokyo, Japan E-mail address: [email protected] (Y. Mukai).
Purpose of study: Botulinum toxins type A are classified into four subtypes (A1-A4), and only products belonging to subtype A1(BoNT/A1) are available for clinical use. The properties for the human of subtype A2-A4 are not known. We may be able to create a therapeutic agent of subtypes A2-A4 origin which is safer than the agent of the subtype A1 origin. We designed this electrophysiological study to compare botulinum toxin subtype A2 (A2 neurotoxin: A2NTX) with onabotulinumtoxinA (BotoxÒ; A1 LL product).
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Methods used: Eight healthy volunteers were enrolled in this study. A2NTX was administered into one extensor digitorum brevis muscle (EDB), and Botox was administered into the contralateral EDB 16 weeks later. The compound muscle action potential (CMAP) amplitudes of EDB, adductor hullcis muscle (AH) and abductor digiti minimi/foot muscle (ADM/foot) were measured to evaluate the paretic effect. CMAP amplitude measurements after BoNT injection were performed on day1, 3, 7, 14, 28, 56, 84 and 112. Summary of results: On day 14 both A2NTX and Botox produced an approximately 70% decline of EDB CMAP amplitude compared to baseline, which then slowly recovered. The CMAP amplitudes of neighbor muscles (AH and ADM/foot) remained unchanged over the study period, indicating that there was no diffusion effect of A2NTX and Botox. Conclusions: Our study showed that the small amounts of A2NTX and Botox had comparable efficacy, titer for humans, and time-to-onset of action. These results support further evaluation of more amounts of A2NTX in clinical use. http://dx.doi.org/10.1016/j.toxicon.2012.07.155
Botulinum toxin type A in hip adductor spasticity in primary progressive multiple sclerosis S. Ochud1o Department of Neurology, Central Clinical Hospital of the Medical University of Silesia, Katowice, Poland E-mail address: [email protected].
Purpose of study: To establish the effectiveness of botulinum toxin type A for treating hip adductor spastic dystonia in primary progressive multiple sclerosis. Methods used: Twenty-two patients with definite primary progressive multiple sclerosis and disabling spastic dystonia affecting the hip adductor muscles of both legs were treated with botulinum toxin type A (BotoxÒ) 200 U, administered by intramuscular injection to these muscles. Patients were assessed at entry, at four weeks (primary analysis time-point) and at 12 weeks post-treatment during 3 years of observation. The injection was repeated every three months. We used the Modified Ashworth Scale, the Tardieu Scale and the Goal Attainment Scale (GAS) for assessing spasticity. The Unified Dystonia Rating Scale (UDRS) and Fahn Marsden Rating Scale (FMRS) were used for assessing dystonia. The Numeric Graphic Rating Scale was used for assessing pain and improvements in daily hygiene. The frequency of spasticity spasm was analyzed. Summary of results: A total of 22 patients suffering from primary progressive multiple sclerosis were recruited; mean EDSS score 7.3; the mean disease duration was eight years. The primary efficacy variablesdpassive hip abduction and distance between the kneesdimproved significantly for all patients. Spasm frequency was reduced for 17 patients. Muscle tone, pain, dystonic posture and improvement in hygiene scores were reduced for all
OnabotulinumtoxinA for treatment of refractory cancer pain S. Mittal, D. Machado, B. Jabbari Department of Neurology, Yale University School of Medicine, New Haven, CT, USA E-mail address: [email protected] (S. Mittal).
Purpose of study: To report the relief from refractory focal post-radiation or post-surgical cancer pain after local treatment with onabotulinumtoxinA. Methods used: Seven patients with moderate to severe focal pain associated with cancer resection or radiation or both as measured by a visual analog scale (VAS score of greater than five) were treated with local injection of onabotulinumtoxinA into the affected region. Patients’ response to treatment was evaluated by the Patient Global Assessment (PGA) scale (satisfaction subset) and the change in VAS pain score. Pain relief was considered significant when there was a drop of at least two or more grades on the VAS and there was satisfaction with treatment as reported by the PGA. Results: All seven patients reported a significant improvement in pain (mean drop in VAS score of 4.8). They described their response on Patient Global Assessment (PGA) as satisfactory (two patients) or very satisfactory (five patients). Six of the seven patients had significant improvement in quality of life. None of them reported any side-effects from the treatment. Four patients had a longterm follow-up (more than a year) that demonstrated consistent improvement with repeated injections. Conclusions: Local injection of onabotulinumtoxinA can significantly reduce refractory focal post-resection and postradiation pain in cancer patients. This observation warrants further investigation in this important pain disorder. http://dx.doi.org/10.1016/j.toxicon.2012.07.154
Electrophysiological study for assessment of botulinum toxin type A2 compared with type A1 in healthy volunteers Y. Mukai a, b, c, Y. Shimatani a, T. Kohda b, T. Sakamoto c, S. Kozaki b, R. Kaji a a
School of Medicine, University of Tokushima Faculty of Medicine, Tokushima, Japan b Department of Veterinary Sciences, School of Life and Environmental Sciences, Osaka Prefecture University, Osaka, Japan c Department of Neurology, National Center Hospital of Neurology and Psychiatry, Tokyo, Japan E-mail address: [email protected] (Y. Mukai).
Purpose of study: Botulinum toxins type A are classified into four subtypes (A1-A4), and only products belonging to subtype A1(BoNT/A1) are available for clinical use. The properties for the human of subtype A2-A4 are not known. We may be able to create a therapeutic agent of subtypes A2-A4 origin which is safer than the agent of the subtype A1 origin. We designed this electrophysiological study to compare botulinum toxin subtype A2 (A2 neurotoxin: A2NTX) with onabotulinumtoxinA (BotoxÒ; A1 LL product).
117
Methods used: Eight healthy volunteers were enrolled in this study. A2NTX was administered into one extensor digitorum brevis muscle (EDB), and Botox was administered into the contralateral EDB 16 weeks later. The compound muscle action potential (CMAP) amplitudes of EDB, adductor hullcis muscle (AH) and abductor digiti minimi/foot muscle (ADM/foot) were measured to evaluate the paretic effect. CMAP amplitude measurements after BoNT injection were performed on day1, 3, 7, 14, 28, 56, 84 and 112. Summary of results: On day 14 both A2NTX and Botox produced an approximately 70% decline of EDB CMAP amplitude compared to baseline, which then slowly recovered. The CMAP amplitudes of neighbor muscles (AH and ADM/foot) remained unchanged over the study period, indicating that there was no diffusion effect of A2NTX and Botox. Conclusions: Our study showed that the small amounts of A2NTX and Botox had comparable efficacy, titer for humans, and time-to-onset of action. These results support further evaluation of more amounts of A2NTX in clinical use. http://dx.doi.org/10.1016/j.toxicon.2012.07.155
Botulinum toxin type A in hip adductor spasticity in primary progressive multiple sclerosis S. Ochud1o Department of Neurology, Central Clinical Hospital of the Medical University of Silesia, Katowice, Poland E-mail address: [email protected].
Purpose of study: To establish the effectiveness of botulinum toxin type A for treating hip adductor spastic dystonia in primary progressive multiple sclerosis. Methods used: Twenty-two patients with definite primary progressive multiple sclerosis and disabling spastic dystonia affecting the hip adductor muscles of both legs were treated with botulinum toxin type A (BotoxÒ) 200 U, administered by intramuscular injection to these muscles. Patients were assessed at entry, at four weeks (primary analysis time-point) and at 12 weeks post-treatment during 3 years of observation. The injection was repeated every three months. We used the Modified Ashworth Scale, the Tardieu Scale and the Goal Attainment Scale (GAS) for assessing spasticity. The Unified Dystonia Rating Scale (UDRS) and Fahn Marsden Rating Scale (FMRS) were used for assessing dystonia. The Numeric Graphic Rating Scale was used for assessing pain and improvements in daily hygiene. The frequency of spasticity spasm was analyzed. Summary of results: A total of 22 patients suffering from primary progressive multiple sclerosis were recruited; mean EDSS score 7.3; the mean disease duration was eight years. The primary efficacy variablesdpassive hip abduction and distance between the kneesdimproved significantly for all patients. Spasm frequency was reduced for 17 patients. Muscle tone, pain, dystonic posture and improvement in hygiene scores were reduced for all