J BUON. 2010 Jul-Sep;15(3):435-46.
Toxic peripheral neuropathy associated with commonly used chemotherapeutic agents.
Argyriou AA,
Zolota V,
Kyriakopoulou O,
Kalofonos HP.
Source
Department of Neurology, Saint Andrew's General Hospital of Patras, and Department of Pathology, University of Patras Medical School, Rion-Patras, Greece.
Abstract
Peripheral neuropathy ranks among the most common non-haematological adverse effects of a number of effective chemotherapeutic agents, including platinum compounds, taxanes and vinca alkaloids. Newer agents, such as bortezomib, thalidomide and lenalidomide, frequently exert similar neurotoxic effects on peripheral nerves. Chemotherapy-induced peripheral neuropathy (CIPN) may result from a variety of mechanisms and may be related to causal factors, such as single dose per course, cumulative dose and risk factors including treatment schedule, prior or concomitant administration of other neurotoxic agents, age and pre-existing peripheral neuropathy of other causes. The symptoms usually begin during chemotherapy and they may even worsen after cessation of treatment. In most of the cases, patients experience positive (pain, paresthesias) or negative (numbness) sensory symptoms in distal extremities in a stocking-and-glove distribution with less prominent motor and autonomic involvement. To date,
several neuroprotective agents including thiols, neurotrophic factors, anticonvulsants and antioxidants have been tested in preclinical models and clinical open label or randomized controlled trials for their ability to prevent or treat symptoms of CIPN. Although several of these agents hold promise as possible neuroprotective factors, clinical data are still controversial and none have as yet robustly been proven effective against CIPN. This review critically looks at the pathogenesis, incidence, risk factors, diagnosis, characteristics and management of peripheral neuropathy associated with commonly used chemotherapeutic agents. We also highlight areas of future research to pursue.
- PMID:
- 20941808
- [PubMed - indexed for MEDLINE]
Clin Pharmacol Ther. 2011 Sep;90(3):377-87. doi: 10.1038/clpt.2011.115. Epub 2011 Aug 3.
Chemotherapy-induced peripheral neuropathy: prevention and treatment.
Pachman DR,
Barton DL,
Watson JC,
Loprinzi CL.
LINK
Source
Department of Medicine, Mayo Clinic, Rochester, Minnesota, USA.
Abstract
Chemotherapy-induced peripheral neuropathy (CIPN) is a common, dose-limiting side effect of many chemotherapeutic agents. Although many therapies have been investigated for the prevention and/or treatment of CIPN, there is no well-accepted proven therapy. In addition, there is no universally accepted, well-validated measure for the assessment of CIPN.
The agents for which there are the strongest preliminary data regarding their potential efficacy in preventing CIPN are intravenous calcium and magnesium (Ca/Mg) infusions and glutathione. Agents with the strongest supporting evidence for efficacy in the treatment of CIPN include topical pain relievers, such as baclofen/amitriptyline/ketamine gel, and serotonin and norepinephrine reuptake inhibitors, such as venlafaxine and duloxetine. Other promising therapies are also reviewed in this paper.
Cutaneous electrostimulation is a nonpharmacological therapy that appears, from an early pilot trial, to be potentially effective in the treatment of CIPN. Finally, there is a lack of evidence of effective treatments for the paclitaxel acute pain syndrome (P-APS), which appears to be caused by neurologic injury.
- PMID:
- 21814197
- [PubMed - indexed for MEDLINE]
Low-level laser therapy for chemotherapy-induced peripheral neuropathy.
Sub-category:
Symptom Management/Supportive Care/Palliative Care
Category:
Patient and Survivor Care
Meeting:
2012 ASCO Annual Meeting
Abstract No:
9019
Citation:
J Clin Oncol 30, 2012 (suppl; abstr 9019)
Author(s): John Muzi Lee, Regan M. Look, Crystal Turner, Stuart K Gardiner, Terry Wagie, Jeremy Douglas, Leslie Sorenson, Laura Evans, Sandra Kirchner, Cyd Dashkoff, Karen Garrett, Nathalie Johnson; Legacy Health Systems, Portland, OR; Compass Oncology, Portland, OR; Legacy Cancer Services, Portland, OR; Legacy Cancer Service, Portland, OR; Legacy Health, Portland, OR; Legacy Health, Portland, OR
Abstract Disclosures
Abstract:
Background: Chemotherapy induced peripheral neuropathy (CIPN) is a common and serious side effect from chemotherapy agents.
Low-level laser light therapy (LLLT) devices were approved in 2002 for pain management. Studies suggest a local release of serotonin, increased mitochondrial ATP production, or anti-inflammatory effects as a mechanism of action. We then questioned whether LLLT would show efficacy in mitigating symptoms caused by CIPN.
Methods: In a single center prospective randomized trial, participants were randomized to receive either treatment with LLLT twice a week for 8 weeks or placebo LLLT twice a week for 4 weeks followed by actual treatment twice a week for 4 weeks. FACT/GOG-NTX, Brief Pain Inventory (BPI -Severity and Interference), SF-36 Quality of Life (Physical and Mental Score), monofilament and function testing (buttoning, coin use and walking) were conducted prior to initiation of therapy, during, at completion, and 2 months after treatment. 20 participants, 16 women and 4 men (average age 58 and 63 respectively), were enrolled between October 2009 and June 2010. 10 patients were randomized to each group. Average time from end of chemotherapy to enrollment was 32.6 months (range 2 - 120 mo).
All patients had neuropathic involvement of the feet. 14 patients had additional involvement of the hands. Results: Compared to baseline, patients receiving any amount of active treatment showed significant improvement at 8 weeks in NTX, BPI, function testing, and SF36 Mental score. Those receiving 4 weeks of placebo treatment showed improvement in only BPI, NTX and SF36 Mental score. At 2-month follow up, all 20 patients showed a significant improvement in walking and SF 36 mental score, suggesting 4 weeks of active treatment improved function. No significant difference in monofilament testing was observed throughout the study in either group.
Direct comparison between 4 or 8 weeks of treatment vs. placebo showed a statistically significant difference in walking function at 2-months. All patients tolerated therapy well without side effects. Conclusions: Low-level laser light therapy improved functional test over placebo and may be a viable option for non-medical management of CIPN. Further study of LLLT in CIPN is warranted.
Ann Pharmacother. 2008 Oct;42(10):1481-5. Epub 2008 Aug 12.
Oral glutamine for the prevention of chemotherapy-induced peripheral neuropathy.
Amara S.
Pharmacy Department, Saint Barnabas Medical Center, 94 Old Short Hills Rd., Livingston, NJ 07039, USA.
samara@sbhcs.com
OBJECTIVE: To evaluate the role of glutamine in the reduction of peripheral neuropathy associated with neurotoxic chemotherapy. DATA SOURCES: Relevant literature was accessed through PubMed (1990-May 2008), using the search terms glutamine, chemotherapy, peripheral neuropathy, neurotoxicity, safety, paclitaxel, platinum compounds, and vinca alkaloids. References in the identified articles were also reviewed for pertinent information. STUDY SELECTION AND DATA EXTRACTION: Studies evaluating the role of oral glutamine for prevention and treatment of chemotherapy-induced peripheral neuropathy (CIPN) were included.
Studies regarding the role of glutamine in the reduction of other radiation- and chemotherapy-related toxicities, such as mucositis, cardiotoxicity, diarrhea, and cachexia, were excluded. DATA SYNTHESIS: CIPN is a significant adverse effect associated with neurotoxic chemotherapy, particularly with taxanes, platinum compounds, and vinca alkaloids. There is no standard therapy for the treatment of this dose-limiting reaction. Glutamine is a nonessential amino acid that is thought to have a neuroprotective role, possibly due to the upregulation of nerve growth factor.
Two studies revealed that oral glutamine was effective in reducing peripheral neuropathy associated with high-dose paclitaxel, as evidenced by a reduction in numbness, dysesthesias, and motor weakness, as well as a smaller loss of vibratory sensation. Another study found that glutamine effectively reduced peripheral neuropathy in patients with colorectal cancer being treated with oxaliplatin, thereby decreasing the need for an oxaliplatin dose reduction. However, data are limited by small sample sizes in these studies and the lack of placebo-controlled, randomized clinical trials. CONCLUSIONS: Larger, well-designed, placebo-controlled trials assessing both safety and efficacy of oral glutamine are warranted before this agent can be definitively recommended for the prevention of CIPN in patients treated with high-dose paclitaxel or oxaliplatin.
PMID: 18698011 [PubMed - indexed for MEDLINE]
Mixed Success in Search for Solution to Chemo-Induced Sensory Neuropathy
LINK
Elsevier Global Medical News. 2009 Jun 19, D McNamara
ORLANDO (EGMN) - Significant, moderate, and no improvement at all—these are results of three studies that assessed strategies to prevent or minimize sensory neuropathy associated with chemotherapy.
Venlafaxine significantly reduced neuropathic pain compared to placebo in patients treated with oxaliplatin in one study. A topical gel of baclofen, amitriptyline, and ketamine brought moderate relief to patients in another experiment. But vitamin E failed to reduce incidence of neuropathy in a different trial.
With no proven pharmacologic treatments, chemotherapy-induced peripheral neuropathy (CIPN) is often a dose-limiting toxicity. "Chemotherapy-induced neuropathy ... is a very, very complex side effect where we have little understanding of the underlying pathophysiology," said study discussant Charles S. Cleeland, Ph.D., chair of the Department of Symptom Research at M.D. Anderson Cancer Center, Houston. He had no relevant disclosures.
Investigators looking for solutions to this problem presented the studies at the annual meeting of the American Society of Clinical
Oncology:
Venlafaxine Succeeds in Small Trial
Dr. Jean-Philippe Durand presented prospective, double-blind, randomized
phase III study results that showed venlafaxine (Effexor) significantly reduced neuropathic pain associated with oxaliplatin (Eloxatin) compared to placebo. More than 70% of patients had colorectal cancer.
In this EFFOX study, Dr. Durand and his associates found that 31% of 22 patients treated with
venlafaxine (used off-label) were free of acute neuropathy symptoms for at least five days - compared with a 5% of 23 patients given placebo. "So we achieved the primary endpoint," Dr. Durand, a medical oncologist at Cochin Hospital in Paris, said in an interview. He and his coauthors had no disclosures.
A secondary endpoint was a response of 50% or greater. This was achieved by 69% of the venlafaxine group and 26% of the placebo group. Neurotoxicity was assessed using a rating scale of symptom relief and the Neuropathic Pain Symptom Inventory.
Patients had a mean age of 68 years and were randomized October 2005 to May 2008 to placebo or
50 mg of venlafaxine one hour prior to oxaliplatin infusion, followed by 37.5 mg twice a day of venlafaxine extended-release from day 2 to day 11. Side effects associated with venlafaxine included emesis in 4 patients and somnolence in 3 patients. FOLFOX (folinic acid [leucovorin], fluorouracil, and oxaliplatin and GEMOX (gemcitabine and oxaliplatin) were the most common chemotherapy regimens.
"Dosing was interesting in that they started it prior to therapy and kept it up for ten days," Dr. Cleeland said.
"The interesting and intriguing point of this [study] was in terms of the duration of the effect," Dr. Cleeland said.
They reported 33% in the placebo group versus essentially nobody in the treated group reporting neuropathy at three months. So the signal is there ... and I would say it's worth pursuing."
"Venlafaxine could prevent, maybe, the chronic neuropathy," Dr. Durand said. "Neurotoxicity is the dose-limiting toxicity with oxaliplatin, so maybe [with this approach] we can give more."
Topical Gel Reduces Symptoms
Debra L. Barton, R.N., Ph.D., and colleagues from the North Central Cancer Treatment Group (NCCTG) demonstrated that a
topical combination of baclofen, amitriptyline, and ketamine (BAK) moderately improved symptoms of chemotherapy-induced sensory neuropathy in a double-blind, randomized, placebo-controlled study of 208 patients.
Prior to the trial, there were only limited data, including case reports, to support use of BAK to treat peripheral sensory neuropathy, Dr. Barton said, recalling, "I'm pretty skeptical. Someone called me and said I should study this for chemotherapy-related perioperative neuropathy."
So she did. The investigators randomized 104 patients to 10 mg of baclofen, 40 mg of amitriptyline HCl, and 20 mg of ketamine compounded in a pluronic lecithin organogel and another 104 patients to placebo in a gel. All participants had CIPN rated greater than 4 on a scale of 1 to 10, lasting at least one month.
Primary outcome was change in the sensory subscale of the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire - CIPN20 at 4 weeks compared to baseline. This and other measures favored treatment (See Table). The study, Trial NO6CA, was sponsored by the National Cancer Institute.
The topical gel was well tolerated with no significant difference in adverse effects compared with placebo. There was no evidence of systemic toxicity, said Dr. Barton, associate professor of oncology at the Mayo Clinic College of Medicine in Rochester, Minn. She had no disclosures.
Owing to the investigational new drug status, the Food and Drug Administration regulated the BAK concentrations in the study.
"Even though we had positive results, we did not have as great an effect ... as a compounding pharmacist who uses higher concentrations and uses it more frequently," Dr. Barton said in an interview. "We want to go back to the FDA to get increased doses."
Dr. Cleeland described this study as very interesting. "The idea of a topical is exciting because perhaps any problems with drug interactions might be helped by handling it in that way," he said, adding, "We have a signal again I would say, and perhaps worth pursuing."
No Less Neuropathy With Vitamin E
Nurse practitioner Lisa Kottschade found that
twice-daily vitamin E did not significantly reduce incidence of chemotherapy-induced sensory neuropathy in a phase III, double-blind, and placebo controlled study of 189 patients.
Ms. Kottschade was disappointed with the findings. "Basically, it was negative, it didn't work," she said in an interview. "There was no significant difference between the two arms in terms of neuropathy." The results contrast with promising data from small, pilot studies in the literature.
Dr. Cleeland said the study was "beautifully presented" and described it as "an honest, frank, negative trial [that] can't be more negative."
He added, "At least at this dose, if you think about using vitamin E, I think perhaps you ought to think again."
Patients undergoing treatment with neurotoxic chemotherapy between December 2006 and December 2007 took either 400 mg of vitamin E twice daily or placebo. The primary endpoint, incidence of grade 2+ sensory neuropathy toxicity was 34% in the vitamin E group and 29% in the placebo arm (P = .42).
The investigators also found no significant differences between groups on secondary outcomes: time to onset of neuropathy, chemotherapy dose reductions attributed to neuropathy, or neuropathy symptoms reported via patient questionnaire.
The treatment was well tolerated overall. "The vitamin E was not toxic but did not prevent sensory neuropathy," said Ms. Kottschade, assistant professor of oncology at Mayo Clinic College of Medicine, also in Rochester, Minn.
Gan To Kagaku Ryoho. 2009 Sep;36(9):1565-8.
[A case of paclitaxel-induced peripheral neuropathy successfully treated by H2-blocker, lafutidine]
[Article in Japanese]
Matsumura T,
Imamura H,
Kishimoto T,
Miyazaki Y,
Fujii C,
Fujino M,
Yasui Y,
Anami S,
Sumita R,
Takada N,
Fujita Y,
Furukawa H.
Dept. of Surgery, Sakai Municipal Hospital.
We report a
75-year-old female gastric cancer patient with paclitaxel-induced peripheral neuropathy, which was successfully treated by the H2-blocker, lafutidine. From December 2007, she underwent second-line chemotherapy using paclitaxel (80 mg/m/2 day 1, 7, 14/28 days) for peritoneal dissemination which had been refractory to first-line chemotherapy using S-1 (80 mg/m / 2, day 1-28/42 days). After 2 courses, CT showed a complete response (CR) of the peritoneal dissemination. However, at the same time peripheral neuropathy appeared, which was aggravated to grade 3 at the 6th course.
Beginning with the 7th course, we administered lafutidine (10 mg/day) for peripheral neuropathy, which recovered to grade 1 after 14 days of lafutidine administration. Lafutidine was administered until July 2008, when peripheral neuropathy kept grade 1 without lafutidine. After 9 courses, paclitaxel therapy failed because of general fatigue.
PMID: 19755835 [PubMed - indexed for MEDLINE]
Gynecol Oncol. 2009 Mar;112(3):631-6.
Effect of acetyl-l-carnitine on ovarian cancer cells' proliferation, nerve growth factor receptor (Trk-A and p75) expression, and the cytotoxic potential of paclitaxel and carboplatin.
Engle DB,
Belisle JA,
Gubbels JA,
Petrie SE,
Hutson PR,
Kushner DM,
Patankar MS.
Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, University of Wisconsin School of Medicine and Public Health, 600 Highland Ave., H4-636, Madison, WI 53792-6188, USA.
dbengle3@yahoo.com
OBJECTIVES:
The incidence of chemotherapy induced peripheral neuropathy (CIPN) is 15-25% with platinum and taxanes. CIPN can be permanent and often requires dose reduction or change in chemotherapy. Acetyl-l-carnitine (ALCAR), an ester of l-carnitine, is used to treat CIPN in humans and in animal models. The goals of this study are: 1) examine the effects of ALCAR on ovarian cancer cells, 2) determine if ALCAR affects the cytotoxicity of standard chemotherapy on ovarian cancer cells.Methods:OVCAR-3 and SKOV-3 ovarian cancer lines were incubated in ALCAR containing media. Viability, proliferation, and expression of the nerve growth factor receptors (NGFR) Trk-A and p-75 were determined by flow cytometry.
Cytotoxicity assays examining ALCAR's effect on paclitaxel and carboplatin were done by flow cytometry and infrared plate-reader. RESULTS: Flow cytometry showed no change in percent live (p = 0.87) or proliferation (p = 0.95) of OVCAR-3 cells when comparing controls with up to 100 microM ALCAR. However, there was a slight but significant decrease in the proliferation of SKOV-3 cells incubated at higher ALCAR concentrations (p = < 0.01). Flow cytometry showed no difference in the viability of OVCAR-3 cells when comparing ALCAR: +/- paclitaxel (p = 1), +/- carboplatin (p = 0.8), or both (p = 0.4). Proliferation assays indicated that paclitaxel's cytotoxicity on OVCAR-3 and SKOV-3 cells was unchanged at higher ALCAR concentrations (p = < 0.01-0.4). ALCAR did not affect the expression of NGFR on OVCAR-3 or SKOV-3 cells. CONCLUSION:
ALCAR does not affect the cytotoxicity of paclitaxel or carboplatin. There was no increase in proliferation, or NGFR of OVCAR-3 or SKOV-3 cells exposed to ALCAR.
PMID: 19263582 [PubMed - indexed for MEDLINE]
Support Care Cancer. 2011 Sep;19(9):1473-6. Epub 2011 Jul 16.
Case report of a patient with chemotherapy-induced peripheral neuropathy treated with manual therapy (massage).
Cunningham JE,
Kelechi T,
Sterba K,
Barthelemy N,
Falkowski P,
Chin SH.
LINK
Source
Hollings Cancer Center, and Division of Biostatistics and Epidemiology, Department of Medicine, College of Medicine, Medical University of South Carolina, Charleston, SC 29425, USA.
cunninj@musc.edu
Abstract
PURPOSE:
Chemotherapy-induced peripheral neuropathy (CIPN) is a common, miserable, potentially severe, and often dose-limiting side effect of several first and second-line anti-cancer agents with little in the way of effective, acceptable treatment. Although mechanisms of damage differ, manual therapy (therapeutic massage) has effectively reduced symptoms and improved quality of life in patients with diabetic peripheral neuropathy.
METHODS:
Here, we describe application of manual therapy (techniques of effleurage and petrissage) to the extremities in a patient with grade 2 CIPN subsequent to prior treatment with docetaxel and cisplatin for stage III esophageal adenocarcinoma. Superficial cutaneous temperature was monitored using infrared thermistry as proxy for microvascular blood flow.
RESULTS:
By the end of the course of manual therapy without any change in medications,
CIPN symptoms were greatly reduced to grade 1, with corresponding improvement in quality of life. Improvements in superficial temperature were observed in fingers and toes.
CONCLUSIONS:
Manual therapy was associated with almost complete resolution of the tingling and numbness and pain of CIPN in this patient. Concurrently increased superficial temperature suggests improvements in CIPN symptoms may have involved changes in blood circulation. To our knowledge, this is the first report of using manual therapy for amelioration of CIPN.
- PMID:
- 21766161
- [PubMed - indexed for MEDLINE]
Neuropathy Cure that worked for my wife
My wife had it in her feet and fingers for many weeks after being on Abraxane/Avastin before she tried the treatment suggested of one Vitamin B6 (100mg) in the morning and Alpha Lipoic Acid (300mg) twice a day. After about a week the Neuropathy was gone and she stopped taking anything for it and it has remained completely gone for several months now! Apparently, the Neuropathy can become permanent if you let it go for too long so I would highly suggest asking your doctor about the above treatment. Some say it can interfere with the chemo...but this was not the case in my wife's situation as she received a great response from the chemo treatment as far as her tumors shrinking and disappearing.
Clin Med Insights Oncol. 2010 Apr 28;4:35-41.
Melatonin, a promising role in taxane-related neuropathy.
Nahleh Z,
Pruemer J,
Lafollette J,
Sweany S.
Karmanos Cancer Institute, Division of Hematology-Oncology, Wayne State University 4100 John R, 4HWCRC, Detroit, MI 48201, USA.
FREE TEXT
Abstract
PURPOSE: Melatonin has neuroprotective effects in animal studies and has been suggested to decrease adverse reactions of chemotherapy including neuropathy. This pilot trial aimed at assessing whether melatonin, given during taxane chemotherapy for breast cancer, will decrease the incidence and/or severity of neuropathy.
METHODS: Twenty two consecutive patients beginning chemotherapy for breast cancer with paclitaxel, or docetaxel were enrolled.
Patients received melatonin 21 mg daily at bedtime. Incidence and severity of neuropathy were assessed using neurological examinations, toxicity assessment per NCI-CTC 3.0 scale and FACT-Taxane quality of life questionnaire.
RESULTS: Neuropathy was seen in 45% (n = 10) of patients, 23% (n = 6) grade 1 and 22% (n = 5) Grade 2 neuropathy. No grade 3 neuropathies were reported. The majority (55%) of all patients reported no neuropathy. Compliance with melatonin (>60% of dose) was seen in most patients (86%) No patient reported daytime sedation. The median FACT-Taxane quality of life end of study score was 137, with only a 0.5 median decline from baseline.
CONCLUSION:
Patients receiving melatonin during taxane chemotherapy had a reduced incidence of neuropathy. Melatonin may be useful in the prevention or reduction of taxane-induced neuropathy and in maintaining quality of life. Larger trials are warranted to further explore the role of melatonin in neuropathy treatment and prevention.
PMID: 20567633 [PubMed - in process]PMCID: PMC2883241Free PMC Article
Indian J Palliat Care. 2010 Jan;16(1):48-51.
Radio Frequency Ablation in Drug Resistant Chemotherapy-induced Peripheral Neuropathy: A Case Report and Review of Literature.
Yadav N,
Philip FA,
Gogia V,
Choudhary P,
Rana SP,
Mishra S,
Bhatnagar S.
Free PMC Article
Source
Dr. B. R. Ambedkar, Institute Rotary Cancer Hospital, All India Institute of Medical Sciences, Ansari Nagar, New Delhi-110 029, India.
Abstract
Chemotherapy-induced peripheral neuropathy (CIPN) is a frequently encountered complication. It can result from a host of agents. Various modalities of treatment have been advocated, of which a novel method is radio frequency ablation. A
63-year-old male, a case of carcinoma prostrate with bone metastases, presented with tingling and numbness in right upper limb. He was given morphine, gabapentin and later switched to pregabalin, but medications provided only minor relief. Initially he was given stellate ganglion block, then radiofrequency ablation of dorsal root ganglion was done, but it failed to provide complete relief.
Pulsed radiofrequency ablation (PRF) was then done for 90 seconds; two cycles each in both ulnar and median nerve. After the procedure the patient showed improvement in symptoms within four to five hours and 80% relief in symptoms. We conclude that PRF can be used for the treatment of drug resistant CIPN.
- PMID:
- 20859472
- [PubMed]
- PMCID:
- PMC2936083
Neuropharmacology. 2011 Sep;61(4):600-7. Epub 2011 May 11.
Lacosamide has protective disease modifying properties in experimental vincristine neuropathy.
Geis C,
Beyreuther BK,
Stöhr T,
Sommer C.
Source
Department of Neurology, University of Würzburg, Würzburg, Germany.
Geis_C@klinik.uni-wuerzburg.de
LINK
Abstract
Pain and paresthesias are the most common symptoms of chemotherapy induced painful neuropathy (CIPN). Current treatment and preventive strategies of CIPN are ineffective, and the neuropathy may lead to discontinuation of anti-tumor therapy. Here we used experimental vincristine-induced neuropathy in rats to evaluate the disease modifying potential of lacosamide using a sustained release formulation and the acute treatment effects of a rapid release formulation. Pain behavior was assessed by withdrawal responses to von Frey hairs, acetone drops, the Randall-Selitto device, and to radiant heat. Neuropathy was assessed using electrophysiological recordings. Preventive lacosamide treatment (30 mg/kg subcutaneously b.i.d. for 17 days) was well tolerated, and pharmacokinetic analysis revealed a peak plasma concentration 2 h post-injection with a plasma half-life of approximately 3 h. Rats treated with lacosamide, in contrast to vehicle treated rats, did not develop vincristine-induced cold allodynia. Neurophysiology showed a delayed F-wave latency in vehicle treated rats, which was not present in lacosamide treated animals. We could thus demonstrate a protective disease modifying potency of lacosamide in an animal model of CIPN.
Lacosamide may be a promising candidate for preventive treatment of CIPN in patients receiving chemotherapy with vinca alkaloids or platinum drugs.
Copyright © 2011 Elsevier Ltd. All rights reserved.
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