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Old 06-10-2011, 03:49 PM
gdpawel gdpawel is offline
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Default Peripheral Neuropathy

Perhaps a little understanding of what peripheral neuropathy is can help you deal with it.

There are three major groups of nerves in the human body.

1. The peripheral nerves that carry information to and from the limbs.

2. The nerves that supply the bowels and other internal organs.

3. The nerves of the head which connect to the ears, eyes, taste buds, etc.

Nerves in any or all of these major groups can be affected by certain chemotherapy drugs.

Nerves are vulnerable to many kinds of damage. They can be damaged by certain cancers. This may be caused by the cancer cells producing a particular kind of biological agent that interferes with the function of the nerves.

Sometimes, they can be damaged by drugs used in chemotherapy treatment. The chemotherapy drugs that most likely cause nerve damage are the vinca alkaloids, platinum drugs and the taxanes. These drugs have the potential of interfering with nerve function.

You may notice symptoms in different areas of your body depending on which groups of nerves are affected.

Symptoms in the hands and feet happen when peripheral nerve damage happens. The first sign of nerve damage is usually a feeling of tingling and numbness like what you experience when your foot goes to sleep after you've been sitting for a long time in an uncomfortable position.

If the problem progresses further, it often produces weakness of the muscles, resulting in loss of strength at the wrist or the ankle. You will notice difficulty in doing up buttons and picking up coins. You may notice that you will tend to trip while walking up stairs or dragging your feet and tend to have a wide-based gait. In severe cases, the weakness may be so severe that you will need a wheelchair.

When the nerves in the bowel are affected, constipation is the earliest sign. In a few people, the abdomen becomes bloated with a distended bowel that is basically paralyzed.

Some of the nerves in the head can also be affected. Platinum drugs can affect the auditory nerve and cause loss of hearing and tinnitus(ringing in the ears). Vision can very occasionally be affected.

A lot depends on how quickly your cancer treatment can be stopped. Sometimes the need for treatment is more urgent then the residual nerve damage. Sometimes, the balance between benefit from the drug and the side effect of nerve damage is more finely balanced.

Once treatment has been stopped, recovery is usually slow. It may take months to get even partial improvement and often there will be some residual impairment, either a motor weakness or a sensory numbness or both. Recovery is slower in the feet and legs than in the hands and arms.

There is no specific treatment that enhances nerve recovery. There are no drugs that will directly stimulate nerve regeneration or recovery. If you have severe and prolonged pain, then the pain may require narcotics often combined with antidepressants. In some cases, certain types of anticonvulsants would be helpful.

Treatment options are subjects that you should discuss with your doctor, so you have accurate expectations of potential benefits and side effects.

Chemotherapy drugs that can cause neuropathy. NCI lists these as most likely to do so:

Cisplatinum (Platinol)
Carboplatin (Paraplatin)
Vincristine (Oncovin)
Vinblastine (Velban)
Etoposide/VP-16 (VePesid)
Cytarabine (Cytosar, Ara-C)
Hexamethylmelamine (Hexalen)
Suramin
Paclitaxel (Taxol) and Docetaxel (Taxotere)
Other medications reported to contribute to neuropathy include oxaliplatin (Eloxatin), gemcitibine (Gemzar) and thalidomide (Thalomid).
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Old 06-10-2011, 03:51 PM
gdpawel gdpawel is offline
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Default Chemotherapy-induced peripheral neuropathy

Cancer patients need to add to their repertoire of specialists for their disease. A Physical Medicine and Rehabilitation Specialist for neuropathy, a Pulmonary Specialist for radiation pneumonitis, a Neurologist for leukoencephalopathy or worse, radiation-induced necrosis, or an Endocrinology & Metabolism Specialist, depending on what actually could be wrong with the patient.

Oncologists need to work more closely than ever with dermatologists, endocrinologists and gastroenterologists when targeted drugs (target specific mutations) and immunotherapies (stimulate the body's immune system to attack cancer) are used. Although less toxic then chemo, these new treatments can still cause side effects (skin problems, diarrhea, high blood pressure, pituitary malfunction, 103 to 105 degree fevers, shortness of breath, colitis), some life-threatening, according to the National Cancer Institute. As with chemo, sometimes patients need to take breaks from these drugs or take them at lower doses.

While there is no specific treatment that enhances nerve recovery or regeneration, pain may be tolerated by narcotics, antidepressants or anticonvulsants.

I've written before on the boards that anecdotally, drugs like Neurontin are used off-label. Most drugs are prescribed off-label. One must be cautious that off-label remedies are fully discussed with patients and must not do any harm. A number of practioners like to use Neurontin (gabapentin) for all neuropathy. It is already used for diabetic neuropathy and neuropathic pain and (after a work-up and ruling out other causes) they found this to work. But again, do no harm.

As far as I know, there hasn't been any studies of taxane-induced neuropathy. However, recently, there is a SWOG trial aimed at studying neuropathy. It is a Phase III trial that just started in September 2009 that will involve 380 participants and is available at 180 locations. Unfortunately, it excludes those with prior taxane therapy.

Acetyl-L-Carnitine in Preventing Neuropathy in Women With Stage I, Stage II, or Stage IIIA Breast Cancer Undergoing Chemotherapy

[url]http://clinicaltrials.gov/ct/show/NCT00775645

I wrote years ago about Bionumerik boosting about its new drug Tavocept, that was aimed at preventing or reducing common and serious side effects, particularly nerve and kidney damage, associated with taxane and platinum drugs. Very little had been accomplished to prevent or reduce chemotherapy-induced toxicities, but they had a new product and began testing it.

Trends in the Treatment of Chemotherapy-Induced Peripheral Neuropathy

[url]http://www.practiceupdate.com/ExpertOpinion/368
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Last edited by gdpawel : 04-12-2015 at 02:03 PM. Reason: additional info
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Old 06-10-2011, 03:54 PM
gdpawel gdpawel is offline
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Default Neurontin for pain management/neuropathy

I've written before that anecdotally, drugs like Neurontin are used off-label. Most drugs are prescribed off-label. One must be cautious that off-label remedies are fully discussed with patients and must not do any harm. A number of practioners like to use Neurontin (gabapentin) for all neuropathy. It is already used for diabetic neuropathy and neuropathic pain and (after a work-up and ruling out other causes) they found this to work. But again, do no harm.

Kay Dickerson, an epidemiologist at Johns Hopkins University, has a new study in the New England Journal of Medicine comparing the outcomes of a dozen studies of Neurontin (gabapentin) to their original protocols. It turns out the researchers working on the Pfizer/Parke-Davis drug changed the endpoints in eight of those trials while they were underway.

MedPage Today has a good recap:

[url]http://www.medpagetoday.com/Neurology/PainManagement/16952

From the New England Journal of Medicine:

Outcome Reporting in Industry-Sponsored Industry-Sponsored Trials of Gabapentin for Off-Label Use

S. Swaroop Vedula, M.D., M.P.H., Lisa Bero, Ph.D., Roberta W. Scherer, Ph.D., and Kay Dickersin, Ph.D.


ABSTRACT

Background There is good evidence of selective outcome reporting in published reports of randomized trials.

Methods We examined reporting practices for trials of gabapentin funded by Pfizer and Warner-Lambert's subsidiary, Parke-Davis (hereafter referred to as Pfizer and Parke-Davis) for off-label indications (prophylaxis against migraine and treatment of bipolar disorders, neuropathic pain, and nociceptive pain), comparing internal company documents with published reports.

Results We identified 20 clinical trials for which internal documents were available from Pfizer and Parke-Davis; of these trials, 12 were reported in publications. For 8 of the 12 reported trials, the primary outcome defined in the published report differed from that described in the protocol. Sources of disagreement included the introduction of a new primary outcome (in the case of 6 trials), failure to distinguish between primary and secondary outcomes (2 trials), relegation of primary outcomes to secondary outcomes (2 trials), and failure to report one or more protocol-defined primary outcomes (5 trials). Trials that presented findings that were not significant (P0.05) for the protocol-defined primary outcome in the internal documents either were not reported in full or were reported with a changed primary outcome. The primary outcome was changed in the case of 5 of 8 published trials for which statistically significant differences favoring gabapentin were reported. Of the 21 primary outcomes described in the protocols of the published trials, 6 were not reported at all and 4 were reported as secondary outcomes. Of 28 primary outcomes described in the published reports, 12 were newly introduced.

Conclusions We identified selective outcome reporting for trials of off-label use of gabapentin. This practice threatens the validity of evidence for the effectiveness of off-label interventions.

Source Information

From the Center for Clinical Trials, Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore (S.S.V., R.W.S., K.D.); and the Department of Clinical Pharmacy and Institute for Health Policy Studies, University of California at San Francisco, San Francisco (L.B.).
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  #4  
Old 06-10-2011, 03:55 PM
gdpawel gdpawel is offline
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Default Taxane-induced Peripheral Neuropathy

Researchers have identified a genetic biomarker that can predict a patient's likelihood of experiencing taxane-induced peripheral neuropathy, which is characterized by a pain and numbness in fingers and toes and can keep patients from receiving the intended amount of their therapy, complicating treatment.

The marker in the RWDD3 gene. The findings came from a large genome-wide association study of 2,204 early-stage breast cancer patients enrolled in a clinical trial that used weekly paclitaxel for 12 weeks in all arms. This marked the first time a genetic biomarker has been reported for taxane-induced neuropathy.

Dr. Bryan P. Schneider of the Simon Cancer Center at Indiana University, Indianapolis, and his colleagues, looked for variations in DNA called single nucleotide polymorphisms (SNPs) in each patient. During the study and follow-up period, 613 of the patients reported experiencing grade 2-4 neuropathy.

By looking at more than 1.2 million SNPs in each patient, Dr. Schneider and his colleagues were able to identify genetic subgroups most likely to develop neuropathy.

Those who carried two normal nucleotides in a specific regulatory gene had a 27% chance of experiencing neuropathy. But those who carried one normal nucleotide and one SNP had a 40% chance and those who carried two SNPs had a 60% chance.

The researchers also found that older patients and blacks were much more likely to have peripheral neuropathy. The likelihood of neuropathy increased 12.9% with every decade of age. Blacks saw a two-fold increase in the likelihood of developing neuropathy.

The study was funded by the Eastern Cooperative Oncology Group under the National Cancer Institute.

A Yale School of Medicine study found a molecular basis for the peripheral pain caused by taxanes. It appears to be caused when the drug binds to a protein and initiates improper calcium signaling. This response leads to side effects such as acute hypersensitivity, slower heart rhythms, tingling, numbness, and other symptoms (PNAS 104: 11103-11108 June 20, 2007). These serious side effects limit the drug's effectiveness. Peripheral pain becomes worse with continued use and increased dosages lead to persistent and irreversible pain.

The binding protein is called neuronal calcium sensor (NCS-1). When paclitaxel (taxol) binds to NCS-1, it makes the cell more sensitive to normal signals and increases the magnitude and frequency of changes in calcium. Over time, increased calcium levels activate an enzyme (calpain) that degrades proteins, especially NCS-1. Calcium signals are needed for nerves to be stimulated and to respond and the loss of NCS-1 makes it more difficult to generate any calcium signals. While the loss of NCS-1 stops the protein interaction that is causing the inappropriate calcium signals, it also decreases the ability to have normal responses.

Here is some information about natural strategies to reduce Neuropathy:

1) The behavioral symptoms of neuropathic pain states can be treated successfully, and that partial to complete reversal of associated morphological and neurochemical changes is achievable with artemin (Nature Medicine November 2003 Volume 9 Number 11 pp 1383 – 1389).

2) Alpha-lipoic acid (a dietary supplement) is considered safe (Regul Toxicol Pharmacol. 2006 Oct;46(1):29-41. Epub 2006 Aug 14). Also protective for the liver-lipoic acid could offer protection against chloroquine-induced hepatotoxicity. Lipoic acid has a better protective effect when compared with silymarin, a reference drug (Journal of Applied Toxicology Volume 24, Issue 1, Pages 21 - 26).

3) Vitamin B12 (from an article by syndicated columnist Dr. Paul Donohue, To Your Health, in the Palm Beach Post). The recommended daily allowance for vitamin B12 is 2.4 micrograms. Huge doses of vitamin B12 can penetrate the intestinal wall. But, B12 deficiency is an uncommon cause of burning feet.

3) Urea containing preparation appears to be an excellent choice for the prevention and treatment of capecitabine induced hand foot syndrome. This minimizes drug delays, schedule interruptions and maintains the dose density. Owing to reduced morbidity, the drug tolerance and acceptance is considerably improved (ASCO 2004 Abstract No: 8105).

4) Oral Glutamine is effective for preventing Oxaliplatin-induced Neuropathy in Colorectal cancer patients (The Oncologist, Vol. 12, No. 3, 312-319, March 2007; doi:10.1634/theoncologist.12-3-312).

5) A study published in a recent issue of the Journal of Alternative and Complementary Medicine has found that acupuncture can reduce pain and peripheral neuropathy in HIV-infected individuals, especially when treatment is directed at a patient's specific symptoms (Journal of Alternative and Complementary Medicine 2004;10(3):449-455).

6) While nerve conduction velocity did not improve, vibration perception increased. Clinical symptoms also improved in groups treated with acetyl-L-carnitine compared to placebo. Participants who received 1,000 milligrams acetyl-L-carnitine thrice daily demonstrated significant improvement in pain at the study’s midpoint and conclusion.

7) Neuroprotective Conclusion: Supplementation of patients receiving cisplatin chemotherapy with vitamin E decreases the incidence and severity of peripheral neurotoxicity (Journal of Clinical Oncology, Vol 21, Issue 5 (March), 2003: 927-931).
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Last edited by gdpawel : 09-16-2015 at 11:38 PM. Reason: Additional information
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Old 07-07-2011, 03:38 PM
gdpawel gdpawel is offline
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Default How does Taxol work?

Peripheral neuropathy is a recognized side effect of microtuble-targeting agents. Taxol (paclitaxel) is a microtubule stabilising agent that destroys cancer cells by interfering with the cell cycle leading to apoptosis or cell death. Specifically, it interferes with the spindle microtubule dynamics within the cell that ensures the correct alignment of chromosome pairs before they pull apart and become segregated into two daughter cells. Similar to the strings on a puppet, microtubules need to be held at the correct tension for the chromosomes to align. Anything interfering with this process will ultimately cause cell death.

Taxol-treated cells have defects in mitotic spindle assembly, chromosome segregation, and cell division. Unlike other tubulin targeted drugs such as colchicine that inhibit microtubule assembly, however, Taxol stabilizes the microtubule polymer and protects it from disassembly. The inability of the chromosomes to achieve a metaphase spindle configuration leads to a mitotic block in which there is prolonged activation of the mitotic checkpoint with the subsequent triggering of apoptosis or slippage back into the G1-phase of the cell cycle without cell division.

The ability of Taxol to inhibit spindle function is generally attributed to its suppression of microtubule dynamics, but recent studies have demonstrated that suppression of dynamics occurs at concentrations lower than those needed to block mitosis. At the higher antimitotic concentrations, Taxol appears to act by suppressing microtubule detachment from centrosomes, a process normally activated during mitosis. The binding site for Taxol has been shown to reside on the beta-tubulin subunit.

In other words, Taxol gumms up the innards (microtubules) of all rapidly dividing cells (good cells and bad cells). When microtubules get gummed up, the tumor cell commits suicide. A report in the journal International Cancer Research stated that taxane drugs, including Taxol, targets part of the cell cytoskeleton called the tubulin. Tubulin is used to build microtubules, which in turn make up the cell's structure. Destroying it kills the cell, but cancer cells eventually evolve mechanisms to pump out the drugs that do this (resistance). Resistance to anti-tubulin therapies, like Taxol, is a huge problem in many cancers.

It's like a gasoline engine in an automobile. Say the motor is running and for some reason the key in the ignition is broken/jammed and you cannot shut the engine off, and you cannot open the bonnet to cut ignition wires to stop the engine. So the only other way is to pour sugar into the gasoline tank until the motor gummies up and stops running. Now, you shut off the engine the best way you possibly could because of the restrictions. However, while cutting ignition wires would save the engine for another day (replace just the wires), by placing sugar into the gas tank you virtually destroyed the engine, unless you can completely overhaul it.

Sources:

Bharadwaj R., Yu H. (2004). "The spindle checkpoint, aneuploidy, and cancer". Oncogene 23 (11): 2016–27. doi:10.1038/sj.onc.1207374. PMID 15021889.

Brito D. A., Yang Z., Rieder C. L. (2008). "Microtubules do not promote mitotic slippage when the spindle assembly checkpoint cannot be satisfied". J. Cell Biol. 182 (4): 623–9. doi:10.1083/jcb.200805072. PMC 2518701. PMID 18710927.

Jordan MA, Leslie W, Microtubules as a target for anticancer drugs Apr 4, 2004”, "[1]"

Ganguly A, Yang H, Cabral F, Paclitaxel-dependent cell lines reveal a novel drug activity.Mol Cancer Ther. 2010 Nov;9(11):2914-23. Epub 2010 Oct 26.

Who Needs Taxol? [url]http://cancerfocus.org/forum/showthread.php?t=3627

Research into fruit fly cells could lead to cancer insights

New research by scientists at the University of Exeter has shown that cells demonstrate remarkable flexibility and versatility when it comes to how they divide - a finding with potential links to the underlying causes of many cancers.

The study, published in Developmental Cell, describes a number of routes to the formation of a microtubule spindle - the tracks along which DNA moves when a cell divides in order to make two genetically identical cells.

In order to understand the phenomenon, the authors, including Biosciences researchers Dr. James Wakefield, PhD student Daniel Hayward and Experimental Officer in Image Analysis, Dr. Jeremy Metz, combined highly detailed microscopy and image analysis with genetic and protein manipulation of fruit fly embryos.

The innovative research not only describes how the cell can use each pathway in a complementary way, but also that removal of one pathway leads to the cell increasing its use of the others. The researchers also identified that a central molecular complex - Augmin - was needed for all of these routes.

The authors were the first to identify that each of four pathways of spindle formation could occur in fruit fly embryos.

It was previously thought that, in order for chromosomes - packages containing DNA - to line up and be correctly separated, microtubules have to extend from specific microtubule-organising centres in the cell, called centrosomes. However, this study found that microtubules could additionally develop from the chromosomes themselves, or at arbitrary sites throughout the main body of the cell, if the centrosomes were missing.

All of these routes to spindle formation appeared to be dependent on Augmin - a protein complex responsible for amplifying the number of microtubules in the cell.

Dr. Wakefield said of the project "We have all these different spindle formation pathways working in humans. Because the cell is flexible in which pathway it uses to make the spindle, individuals who are genetically compromised in one pathway may well grow and develop normally. But it will mean they have fewer routes to spindle formation, theoretically predisposing them to errors in cell division as they age."

The group are currently investigating cancer links in light of these findings.

Citation: University of Exeter. "Research into fruit fly cells could lead to cancer insights." Medical News Today. MediLexicon, Intl., 4 Jan. 2014.
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Last edited by gdpawel : 01-06-2014 at 11:46 AM. Reason: additional info
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Old 12-19-2012, 09:12 PM
gdpawel gdpawel is offline
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Default Cymbalta (duloxetine) for chemo-induced peripheral neuropathy

The antidepressant duloxetine ( Cymbalta) could offer a new option to cancer patients for alleviating pain from chemotherapy-induced peripheral neuropathy (CINP). Positive results from a phase 3 trial, the first in this indication, were hailed as practice-changing here at the 2012 Annual Meeting of the American Society of Clinical Oncology (ASCO).

However, patients should be discouraged from using the acetyl-L-carnitine (ALC) supplement to prevent or treat CINP; a separate study presented produced unexpected negative results.

Ellen Lavoie Smith, PhD, assistant professor of nursing at the University of Michigan in Ann Arbor, and lead author of the duloxetine trial, noted that duloxetine "is the first drug shown to be effective for this terrible pain in a randomized clinical trial." Duloxetine didn't work for every patient, she noted, but it was effective for a majority.

"We now have a treatment that could improve quality of life for many of our patients," she added.

Being able to offer something for CINP pain is important because the pain can be so debilitating that it can lead to a reduction in the chemotherapy dose, which decreases the likelihood of the successful treatment of the cancer.

Many patients experience CINP as a numbness and tingling, a bit like electric shocks, particularly in their hands and feet, but about 30% find it very painful, Dr. Smith said. It can also be chronic, lasting for months or years after the chemotherapy, which can be distressing and disabling, she added.

A variety of interventions are already used for CINP, including gabapentin, pregabapentin, and tricyclic antidepressants, but the use of these is not supported by randomized clinical trial data, she said. In fact, a clinical trial showed that tricyclic antidepressants are not effective, she noted.

A clinician not involved with the study said that he plans to use duloxetine. "We use a lot of platinum drugs, which have known neurotoxicity, and we use gabapentin and pregabapentin in these patients, but after hearing this presentation, I will use [duloxetine]," said Nicholas Vogelzang, MD, who moderated a press briefing in which highlights of this study were presented. Dr. Vogelzang is chair of the ASCO Cancer Communications Committee and medical director at the US Oncology Comprehensive Cancer Centers of Nevada.

"We also use gabapentin," said Hope Rugo, MD, who treats breast cancer patients at the Helen Diller Family Comprehensive Cancer Center at the University of California, San Francisco, and who was at the press briefing.

"We find it useful, despite the lack of data from randomized clinical trials, but it causes somnolence, so duloxetine is a good alternative," she said. ' Dr. Rugo explained that nonsteroidal anti-inflammatory drugs are not effective for this type of pain.

Starting With Lower Dose

Duloxetine is already marketed for use in depression and in painful diabetic peripheral neuropathy.

For the potential indication of CINP, duloxetine was started at a dose of 30 mg daily for 1 week, followed by 60 mg daily for 4 additional weeks. "The gradual dosing was important to reduce side effects, which can include dry mouth, sleepiness, and nausea," Dr. Smith said.

The most commonly reported adverse effect in this trial was moderate to severe fatigue, reported by 11% of patients in the duloxetine group and 3% in the placebo group.

The majority of the 231 patients participating in the trial had either gastrointestinal or breast cancer, and had been treated with taxane or platinum chemotherapy. More than half (58%) had taken oxaliplatin. To enter the study, patients had to score at least 4 on a 10-point CINP pain score.

Patients responses on the Brief Pain Inventory-Short Form (BSI-SF) showed that 59% of patients in the duloxetine group experienced pain reduction, as did 39% in the placebo group.

About one third of patients in both treatment groups reported no change in pain, whereas 11% in the duloxetine group and 28% in the placebo group reported an increase in pain.

Dr. Smith explained that duloxetine is thought to work in this indication by inhibiting the pain-processing pathways in the brain, presumably involving noradrenaline and serotonin; the drug is an inhibitor of these neurotransmitters. She speculated that patients who respond to duloxetine have an abnormality in the pain-processing pathway, and said the next step is to try to find a way to identify these people.

Negative Study of ALC

The findings on the use of the ALC supplement were highlighted in a review session by Debra Barton, PhD, AOCN, RN, associate professor of oncology at the Mayo Clinic in Rochester, Minnesota.

"Patients should be warned against the use of this supplement," she said. In the study, patients were taking the supplement to prevent CINP, but the results showed an increase in its incidence; "most concerning, there was an increase in grade 3 neuropathy," she said.

The ALC study was presented by Dawn Hershman, MD, MS, assistant professor of medicine at the Columbia University Medical Center in New York City. The phase 3 placebo-controlled study, which involved 409 women with breast cancer who were undergoing treatment with taxanes, looked at the effects of ALC 1000 mg taken 3 times daily.

The study set out to confirm previous preclinical and phase 2 data that suggested that ALC, a natural compound involved in tubulin acetylation and neuronal protection, is effective in the prevention and treatment of CINP, the researchers explain.

However, at 12 weeks, there was no evidence that ALC has a positive affect on CINP; at 24 weeks, there was an increase in self-reported CINP. In particular, grade 3/4 neurotoxicity was more frequent in the ALC group than in the placebo group ( P = .04), the researchers note.

"Patients should be discouraged from using ALC and other supplements without proven efficacy," Dr. Hershman and colleagues conclude.

Dr. Smith has disclosed no relevant financial relationships.

2012 Annual Meeting of the American Society of Clinical Oncology: Abstract CRA9013, presented June 5, 2012; Abstract 9018, presented June 4, 2012.

Duloxetine Useful in Chemo Neuropathy, But Avoid ALC. Medscape. Jun 08, 2012.

[url]http://meeting.ascopubs.org/cgi/content/abstract/30/15_suppl/CRA9013?sid=5ab4beb6-1d6f-415a-a026-3139b7b43dc6
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Old 01-19-2016, 12:25 AM
gdpawel gdpawel is offline
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Default Persistent Chemo-Induced Neuropathy Impacts Functioning

Medscape Oncology

Years after the completion of cancer therapy, 45% of female cancer survivors still experience symptoms of chemotherapy-induced peripheral neuropathy (CIPN), which is a common adverse event, according to a new study.

In addition, "women with peripheral neuropathy reported significantly lower physical functioning and significantly more difficulty with tasks of daily living, and nearly twice as many of the women with neuropathy experienced a fall in the previous year," said lead author Kerri Winters-Stone, PhD, a research professor at the School of Nursing at Oregon Health & Science University in Portland.

Neuropathy cannot be dismissed as an adverse event of treatment that goes away, because symptoms persisted for years in nearly half the women in this study, she noted.

Dr Winters-Stone spoke at a press conference held in advance of the Cancer Survivorship Symposium Advancing Care and Research in San Francisco, where she will present the findings.

"CIPN is often under-recognized and probably under-reported," said presscast moderator Merry-Jennifer Markham, MD, associate professor of medicine at the University of Florida in Gainesville. "Many of our chemotherapy treatments for a variety of cancers such as lung cancer, lymphoma, ovarian cancer, breast cancer, and colon cancer, just to name a few include agents that can cause CIPN."

The neuropathy our patients are experiencing is not just a bothersome symptom.

"This study is important because it highlights the fact that the neuropathy our patients are experiencing is not just a bothersome symptom," she said. "It not only impacts survivors' physical function for years to come, it also puts them at risk for falls and the associated morbidity."

Long-term Effects of CIPN

An estimated 57% to 83% of patients will have signs of CIPN at some point during or after their care, depending of the type of chemotherapy received, Dr Winters-Stone noted.

However, information on the long-term effects of CIPN are rare. "The studies that quantify the function consequences of CIPN among cancer survivors tend to use self-report of the symptom itself and of functional ability," she explained. "Other studies tend not to use objective measures or feature small sample sizes."

For their study, Dr Winters-Stone and her colleagues used baseline assessments from 678 female cancer survivors who were enrolled in exercise trials at their institution.

Women with symptoms of CIPN were compared with asymptomatic women on the following measures: maximal leg press strength; timed chair stand; physical performance battery; gait patterns; step number; stride length; base of support; percentage of time in double support; self-reported physical function and disability; and falls in the previous year. Group comparisons were made using analysis of covariance adjusted for time since diagnosis and cancer site (breast or other).

The final cohort involved 462 women (mean age, 62 6 years; median time since diagnosis, 5.8 4.1 years), 210 (45%) of whom reported experiencing CIPN symptoms and 252 (55%) of whom did not.

Women reported experiencing symptoms such as loss of feeling in hands and feet and difficulty undertaking activities of daily life.

There were significant differences between the two groups on all measures except maximal strength and base of support during a walk.

The risk of falling was 31% for women with CIPN and 19% for those without symptoms. "That risk is nearly twice as high," Dr Winters-Stone pointed out.

The differences in physical function (5 points) and disability (7 points) were clinically meaningful, and a difference in chair stand time of more than 12 seconds in the CIPN group was associated with an increased risk for falls.

"Strategies to reduce the likelihood of developing the symptoms, and rehabilitation for those who have the symptoms, are sorely needed," Dr Markham said.

This study was funded by the National Cancer Institute, the American Cancer Society, and the Susan G. Komen for a Cure Foundation. Dr Winters-Stone and Dr Markham have disclosed no relevant financial relationships.

Cancer Survivorship Symposium (CSS) Advancing Care and Research: Abstract 130. Presented January 15, 2016.
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