Rich66
11-21-2009, 01:32 AM
Ann Pharmacother. (http://javascript%3Cb%3E%3C/b%3E:AL_get%28this,%20%27jour%27,%20%27Ann%20Pharm acother.%27%29;) 2008 Oct;42(10):1481-5. Epub 2008 Aug 12.
Oral glutamine for the prevention of chemotherapy-induced peripheral neuropathy.
Amara S (http://www.ncbi.nlm.nih.gov/pubmed?term=%22Amara%20S%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsP anel.Pubmed_RVAbstract).
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 (http://www.oncologystat.com/news-and-viewpoints/news/Mixed_Success_in_Search_for_Solution_to_Chemo-Induced_Sensory_Neuropathy_US.html)
Elsevier Global Medical News. 2009 Jun 19, D McNamara
<!--startindex-->
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. (http://javascript%3Cb%3E%3C/b%3E:AL_get%28this,%20%27jour%27,%20%27Gan%20To%20 Kagaku%20Ryoho.%27%29;) 2009 Sep;36(9):1565-8.
[A case of paclitaxel-induced peripheral neuropathy successfully treated by H2-blocker, lafutidine]
[Article in Japanese]
Matsumura T (http://www.ncbi.nlm.nih.gov/pubmed?term=%22Matsumura%20T%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsP anel.Pubmed_RVAbstract), Imamura H (http://www.ncbi.nlm.nih.gov/pubmed?term=%22Imamura%20H%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsP anel.Pubmed_RVAbstract), Kishimoto T (http://www.ncbi.nlm.nih.gov/pubmed?term=%22Kishimoto%20T%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsP anel.Pubmed_RVAbstract), Miyazaki Y (http://www.ncbi.nlm.nih.gov/pubmed?term=%22Miyazaki%20Y%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsP anel.Pubmed_RVAbstract), Fujii C (http://www.ncbi.nlm.nih.gov/pubmed?term=%22Fujii%20C%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsP anel.Pubmed_RVAbstract), Fujino M (http://www.ncbi.nlm.nih.gov/pubmed?term=%22Fujino%20M%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsP anel.Pubmed_RVAbstract), Yasui Y (http://www.ncbi.nlm.nih.gov/pubmed?term=%22Yasui%20Y%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsP anel.Pubmed_RVAbstract), Anami S (http://www.ncbi.nlm.nih.gov/pubmed?term=%22Anami%20S%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsP anel.Pubmed_RVAbstract), Sumita R (http://www.ncbi.nlm.nih.gov/pubmed?term=%22Sumita%20R%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsP anel.Pubmed_RVAbstract), Takada N (http://www.ncbi.nlm.nih.gov/pubmed?term=%22Takada%20N%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsP anel.Pubmed_RVAbstract), Fujita Y (http://www.ncbi.nlm.nih.gov/pubmed?term=%22Fujita%20Y%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsP anel.Pubmed_RVAbstract), Furukawa H (http://www.ncbi.nlm.nih.gov/pubmed?term=%22Furukawa%20H%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsP anel.Pubmed_RVAbstract).
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. (http://javascript%3Cb%3E%3C/b%3E:AL_get%28this,%20%27jour%27,%20%27Gynecol%20O ncol.%27%29;) 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 (http://www.ncbi.nlm.nih.gov/pubmed?term=%22Engle%20DB%22%5BAuthor%5D), Belisle JA (http://www.ncbi.nlm.nih.gov/pubmed?term=%22Belisle%20JA%22%5BAuthor%5D), Gubbels JA (http://www.ncbi.nlm.nih.gov/pubmed?term=%22Gubbels%20JA%22%5BAuthor%5D), Petrie SE (http://www.ncbi.nlm.nih.gov/pubmed?term=%22Petrie%20SE%22%5BAuthor%5D), Hutson PR (http://www.ncbi.nlm.nih.gov/pubmed?term=%22Hutson%20PR%22%5BAuthor%5D), Kushner DM (http://www.ncbi.nlm.nih.gov/pubmed?term=%22Kushner%20DM%22%5BAuthor%5D), Patankar MS (http://www.ncbi.nlm.nih.gov/pubmed?term=%22Patankar%20MS%22%5BAuthor%5D).
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]
Neuropathy Cure that worked for my wife
(http://www.inspire.com/groups/advanced-breast-cancer/member/edreferral/)
By edreferral (http://www.inspire.com/groups/advanced-breast-cancer/member/edreferral/)
Posted August 20, 2010 at 8:57 pm · 7 replies
In Treatment options (http://www.inspire.com/groups/advanced-breast-cancer/topics/treatment-options/)
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. (http://javascript%3Cb%3E%3C/b%3E:AL_get%28this,%20%27jour%27,%20%27Clin%20Med% 20Insights%20Oncol.%27%29;) 2010 Apr 28;4:35-41.
Melatonin, a promising role in taxane-related neuropathy.
Nahleh Z (http://www.ncbi.nlm.nih.gov/pubmed?term=%22Nahleh%20Z%22%5BAuthor%5D), Pruemer J (http://www.ncbi.nlm.nih.gov/pubmed?term=%22Pruemer%20J%22%5BAuthor%5D), Lafollette J (http://www.ncbi.nlm.nih.gov/pubmed?term=%22Lafollette%20J%22%5BAuthor%5D), Sweany S (http://www.ncbi.nlm.nih.gov/pubmed?term=%22Sweany%20S%22%5BAuthor%5D).
Karmanos Cancer Institute, Division of Hematology-Oncology, Wayne State University 4100 John R, 4HWCRC, Detroit, MI 48201, USA.
FREE TEXT (http://www.ncbi.nlm.nih.gov/pmc/articles/pmid/20567633/?tool=pubmed)
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
Oral glutamine for the prevention of chemotherapy-induced peripheral neuropathy.
Amara S (http://www.ncbi.nlm.nih.gov/pubmed?term=%22Amara%20S%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsP anel.Pubmed_RVAbstract).
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 (http://www.oncologystat.com/news-and-viewpoints/news/Mixed_Success_in_Search_for_Solution_to_Chemo-Induced_Sensory_Neuropathy_US.html)
Elsevier Global Medical News. 2009 Jun 19, D McNamara
<!--startindex-->
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. (http://javascript%3Cb%3E%3C/b%3E:AL_get%28this,%20%27jour%27,%20%27Gan%20To%20 Kagaku%20Ryoho.%27%29;) 2009 Sep;36(9):1565-8.
[A case of paclitaxel-induced peripheral neuropathy successfully treated by H2-blocker, lafutidine]
[Article in Japanese]
Matsumura T (http://www.ncbi.nlm.nih.gov/pubmed?term=%22Matsumura%20T%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsP anel.Pubmed_RVAbstract), Imamura H (http://www.ncbi.nlm.nih.gov/pubmed?term=%22Imamura%20H%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsP anel.Pubmed_RVAbstract), Kishimoto T (http://www.ncbi.nlm.nih.gov/pubmed?term=%22Kishimoto%20T%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsP anel.Pubmed_RVAbstract), Miyazaki Y (http://www.ncbi.nlm.nih.gov/pubmed?term=%22Miyazaki%20Y%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsP anel.Pubmed_RVAbstract), Fujii C (http://www.ncbi.nlm.nih.gov/pubmed?term=%22Fujii%20C%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsP anel.Pubmed_RVAbstract), Fujino M (http://www.ncbi.nlm.nih.gov/pubmed?term=%22Fujino%20M%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsP anel.Pubmed_RVAbstract), Yasui Y (http://www.ncbi.nlm.nih.gov/pubmed?term=%22Yasui%20Y%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsP anel.Pubmed_RVAbstract), Anami S (http://www.ncbi.nlm.nih.gov/pubmed?term=%22Anami%20S%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsP anel.Pubmed_RVAbstract), Sumita R (http://www.ncbi.nlm.nih.gov/pubmed?term=%22Sumita%20R%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsP anel.Pubmed_RVAbstract), Takada N (http://www.ncbi.nlm.nih.gov/pubmed?term=%22Takada%20N%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsP anel.Pubmed_RVAbstract), Fujita Y (http://www.ncbi.nlm.nih.gov/pubmed?term=%22Fujita%20Y%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsP anel.Pubmed_RVAbstract), Furukawa H (http://www.ncbi.nlm.nih.gov/pubmed?term=%22Furukawa%20H%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsP anel.Pubmed_RVAbstract).
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. (http://javascript%3Cb%3E%3C/b%3E:AL_get%28this,%20%27jour%27,%20%27Gynecol%20O ncol.%27%29;) 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 (http://www.ncbi.nlm.nih.gov/pubmed?term=%22Engle%20DB%22%5BAuthor%5D), Belisle JA (http://www.ncbi.nlm.nih.gov/pubmed?term=%22Belisle%20JA%22%5BAuthor%5D), Gubbels JA (http://www.ncbi.nlm.nih.gov/pubmed?term=%22Gubbels%20JA%22%5BAuthor%5D), Petrie SE (http://www.ncbi.nlm.nih.gov/pubmed?term=%22Petrie%20SE%22%5BAuthor%5D), Hutson PR (http://www.ncbi.nlm.nih.gov/pubmed?term=%22Hutson%20PR%22%5BAuthor%5D), Kushner DM (http://www.ncbi.nlm.nih.gov/pubmed?term=%22Kushner%20DM%22%5BAuthor%5D), Patankar MS (http://www.ncbi.nlm.nih.gov/pubmed?term=%22Patankar%20MS%22%5BAuthor%5D).
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]
Neuropathy Cure that worked for my wife
(http://www.inspire.com/groups/advanced-breast-cancer/member/edreferral/)
By edreferral (http://www.inspire.com/groups/advanced-breast-cancer/member/edreferral/)
Posted August 20, 2010 at 8:57 pm · 7 replies
In Treatment options (http://www.inspire.com/groups/advanced-breast-cancer/topics/treatment-options/)
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. (http://javascript%3Cb%3E%3C/b%3E:AL_get%28this,%20%27jour%27,%20%27Clin%20Med% 20Insights%20Oncol.%27%29;) 2010 Apr 28;4:35-41.
Melatonin, a promising role in taxane-related neuropathy.
Nahleh Z (http://www.ncbi.nlm.nih.gov/pubmed?term=%22Nahleh%20Z%22%5BAuthor%5D), Pruemer J (http://www.ncbi.nlm.nih.gov/pubmed?term=%22Pruemer%20J%22%5BAuthor%5D), Lafollette J (http://www.ncbi.nlm.nih.gov/pubmed?term=%22Lafollette%20J%22%5BAuthor%5D), Sweany S (http://www.ncbi.nlm.nih.gov/pubmed?term=%22Sweany%20S%22%5BAuthor%5D).
Karmanos Cancer Institute, Division of Hematology-Oncology, Wayne State University 4100 John R, 4HWCRC, Detroit, MI 48201, USA.
FREE TEXT (http://www.ncbi.nlm.nih.gov/pmc/articles/pmid/20567633/?tool=pubmed)
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