Painful Hands and Feet After Cancer Treatment: Inflammation Affecting the Mind-Body Connection

open access: Editorial

 With the growing number of cancer survivors, it is critical for us to consider toxicities that arise during treatment and do not resolve after treatment ends. Some symptoms continue to burden patients for many years after the cancer has been cured, and chemotherapy-induced peripheral neuropathy (CIPN) is a conspicuous example. CIPN has taken on considerable prominence in the past decade with the more widespread use of the vinca alkaloids, taxanes, platinum analogs, and bortezomib, with an overall incidence estimated at 38%.^1,2 Unfortunately, CIPN has been resistant to multiple strategies aimed at its prevention or treatment once established.^1,3 A critical step in the development of new approaches to management of a cancer treatment–related symptom is to have a better understanding of the mechanism(s) associated with its development, and/or identification of those individuals who are at particularly high risk for experiencing the symptom or having persistent difficulties.^4-7 We are fortunate that there is increasing research interest in symptom science, and the paper by Nudelman et al^{8 (in breast cancer patients)} that accompanies this editorial is an example of this type of work....

 We must be clinically attuned to the complaints our patients voice, and we must make a serious effort to develop prevention and treatment strategies that will reduce the burden of cancer treatment–associated toxicities.

 REFERENCES

1. 1.↵
   1. Hershman DL,
   2. Lacchetti C,
   3. Dworkin RH,
   4. et al.,
   5. American Society of Clinical Oncology

   (2014) Prevention and management of chemotherapy-induced peripheral neuropathy in survivors of adult cancers: American Society of Clinical Oncology clinical practice guideline. J Clin Oncol 32:1941–1967.

   Abstract/FREE Full Text
2. 2.↵
   1. Seretny M,
   2. Currie GL,
   3. Sena ES,
   4. et al.

   (2014) Incidence, prevalence, and predictors of chemotherapy-induced peripheral neuropathy: A systematic review and meta-analysis. Pain 155:2461–2470.

   CrossRefMedlineGoogle Scholar

paywalled- Comparison of weekly versus every 3 weeks paclitaxel in the treatment of advanced solid tumors: A meta-analysis

Comparison of weekly versus every 3 weeks paclitaxel in the treatment of advanced solid tumors: A meta-analysis

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Abstract

Background

Paclitaxel is commonly given as a 3-h infusion every 3 weeks for a variety of malignancies. Several randomized clinical trials comparing weekly paclitaxel with Q3-week (Q3W) have produced mixed results in terms of efficacy and toxicity creating controversy about the ideal dose and schedule.

Methods

A literature search using PubMed, Cochrane Library, and Proceedings of the American Society of Clinical oncology from 1995 to 2011 was performed..........Moderators of cancer types, ethnicity, and paclitaxel dose ratio were analyzed for primary dependent variables.

Results

Ten trials were included....

Conclusion

Weekly paclitaxel has a favorable toxicity profile compared to the current standard of Q3W paclitaxel.

DARA BioSciences Announces New Analysis of Patient Self-Reported Diary Results in a Phase 2a Clinical Trial of KRN5500 in Patients With Cancer and Neuropathic Pain - Drugs.com

http://tinyurl.com/7tmt942

DARA BioSciences Announces New Analysis of Patient Self-Reported Diary Results in a Phase 2a Clinical Trial of KRN5500 in Patients With Cancer and Neuropathic Pain

"....Previous analyses of the study data were based predominantly on patient-reported Numeric Rating Scale (NRS) pain scores collected by healthcare professionals in a clinic setting during weekly visits, whereas this new analysis focused specifically on self-reported daily pain scores from patients' diaries. Responders in this analysis were defined as patients attaining a clinically-meaningful (at least 20%) improvement in mean NRS scores from baseline within any given week. Of the 12 patients who received KRN5500 in this 19-patient trial, 7 (58%) were classified as responders. Further, 5 of the 7 (71%) showed sustained pain relief over several weeks. Of the 7 patients who received placebo, none were responders. Therefore, the new analysis showed a temporal consistency of pain relief in a larger fraction of patients than had been noted in the earlier analysis of weekly clinic-reported pain. These findings are impressive since patients enrolled in this proof-of-concept trial had unrelenting pain at baseline despite the concomitant use of other approved analgesic agents........

 

Acetyl-L-Carnitine Hydrochloride in Preventing Peripheral Neuropathy in Patients With Recurrent Ovarian Epithelial Cancer, Primary Peritoneal Cavi - GOGty Cancer, or Fallopian Tube Cancer Undergoing Chemotherapy - Full Text View - ClinicalTrials.gov

 WebMd:  ACETYL - L - CARNITINE (including other names)

                            ~~~~~~~~~~~~~~~~~~~~

This study is not yet open for participant recruitment.

Verified April 2012 by National Cancer Institute (NCI)

First Received on December 14, 2011.   Last Updated on April 17, 2012   History of Changes

Acetyl-L-Carnitine Hydrochloride in Preventing Peripheral Neuropathy in Patients With Recurrent Ovarian Epithelial Cancer, Primary Peritoneal Cavity Cancer, or Fallopian Tube Cancer Undergoing Chemotherapy - Full Text View - ClinicalTrials.gov

Purpose

RATIONALE: Acetyl-L-carnitine hydrochloride may prevent or lessen peripheral neuropathy caused by chemotherapy. It is not yet known whether acetyl-L-carnitine hydrochloride is more effective compared to a placebo in preventing peripheral neuropathy caused by chemotherapy.

PURPOSE: This randomized phase III trial studies how well acetyl-L-carnitine hydrochloride works compared to a placebo in preventing peripheral neuropathy in patients with recurrent ovarian epithelial cancer, primary peritoneal cancer, or fallopian tube cancer undergoing chemotherapy.

abstract - Journal of Pain and Symptom Management - A Spicamycin Derivative (KRN5500) Provides Neuropathic Pain Relief in Patients With Advanced Cancer: A Placebo-Controlled, Proof-of-Concept Trial

ScienceDirect.com - Journal of Pain and Symptom Management - A Spicamycin Derivative (KRN5500) Provides Neuropathic Pain Relief in Patients With Advanced Cancer: A Placebo-Controlled, Proof-of-Concept Trial

Conclusion

This proof-of-concept study for KRN5500 in patients with advanced cancer and any type of neuropathic pain found gastrointestinal adverse events to be the predominant safety concern. The results also provided the first indication of clinical and statistical efficacy in reducing pain intensity.

abstract: Critical Reviews in Oncology/Hematology - Chemotherapy-induced peripheral neurotoxicity (CIPN): An update

Critical Reviews in Oncology/Hematology - Chemotherapy-induced peripheral neurotoxicity (CIPN): An update

Abstract

The peripheral nervous system can be vulnerable to the toxic action of several drugs since it is not protected as effectively as the central nervous system from noxious exogenous agents. Drug-induced neurotoxicity can affect the nerve fibers or the neuronal bodies (generally the dorsal root ganglia of the primary sensory neurons). Among the neurotoxic drugs antineoplastic agents represent a major clinical problem, given their widespread use and the potential severity of their toxicity. In fact, the peripheral neurotoxicity of antineoplastic agents frequently represents one of their dose-limiting side effects. 

Moreover, even when antineoplastic agents’ peripheral neurotoxicity is not dose-limiting, its onset may severely affect the quality of life of cancer patients and cause chronic discomfort. 

Among the anticancer chemotherapy drugs, platinum derivates, antitubulins, thalidomide and bortezomib can induce the most severe effects on the peripheral nervous system of the treated patients. Therefore, we will review the features of chemotherapy-induced peripheral neurotoxicity (CIPN) resulting from the administration of these drugs with a focus on new classes of promising antineoplastic agents, such as epothilones and proteasome inhibitors.

abstract: Further data supporting that paclitaxel-associated acute pain syndrome is associated with development of peripheral neuropathy - Reeves - 2012 - Cancer - Wiley Online Library

Blogger's Opinion: since this journal is a publication of the ACS then open access should be mandated

Further data supporting that paclitaxel-associated acute pain syndrome is associated with development of peripheral neuropathy

Abstract

BACKGROUND:

Paclitaxel causes an acute pain syndrome (P-APS), occurring within days after each dose and usually abating within days. Paclitaxel also causes a more classic peripheral neuropathy, which steadily increases in severity with increasing paclitaxel total doses. Little detail is available regarding the natural history of these 2 syndromes, or any relationship between them, although a recent publication does provide natural history data about weekly paclitaxel, supporting an association between the severity of P-APS and eventual peripheral neuropathy symptoms.

METHODS:

Patients entering this study were about to receive paclitaxel and carboplatin every 3 weeks. Daily questionnaires were completed for the first week after every chemotherapy dose, and European Organization for Research and Treatment of Cancer, Quality of Life Questionnaire, Chemotherapy-Induced Peripheral Neuropathy 20-item instruments were completed weekly.

RESULTS:

The P-APS severity peaked on day 4 after the initial chemotherapy dose, with 12%, 29%, 23%, and 36% of patients having maximal pain scores of 0, 1 to 4, 5 or 6, or 7 to 10 during the first week after the first dose of therapy, respectively. Patients with P-APS scores of 0 to 4 with the first dose of chemotherapy had less eventual sensory neuropathy than did patients with P-APS scores of 5 to 10 (P = 0.001). With regard to the more peripheral neuropathy, sensory neuropathy was more problematic than was either motor or autonomic neuropathy. Numbness and tingling were more common components of the sensory neuropathy than was pain.

CONCLUSIONS:

Patients with worse P-APS severities appear to have more eventual chemotherapy-induced peripheral neuropathy. This provides support for the concept that P-APS is a form of nerve pathology.

abstract: [Assessment of health-related quality of life in cancer outpatients treated with chemotherapy] Japanese study

[Assessment of health-related quality of life in cancer outpatients treated with chemotherapy].


Abstract
Purpose: 
Few studies have been conducted to elucidate the health-related quality of life(HR-QOL) of cancer outpatients treated with chemotherapy. In this study, we attempted to determine the physical and psychological distress of cancer outpatients treated with chemotherapy.

Methods:
Two-hundred and ninety-six outpatients with various malignancies, including malignant lymphoma, and esophageal, gastric, pancreatic, colon, lung, breast, ovarian, uterine and skin cancers, were investigated using the Japanese version of the M. D. Anderson symptom inventory from March through June 2010 in Tokyo Medical University Hospital.

Results:
The results of the survey questionnaire indicated that 59 patients suffered from fatigue, 56 experienced numbness or tingling, 48 felt drowsy, 39 had low moods, 40 felt distressed, 38 had no appetite, 38 had dry mouth, 37 were in pain, 37 had disturbed sleep, 31 had shortness of breath, 24 had nausea, 17 suffered from vomiting, and 13 patients had memory problems. Furthermore, these symptoms interfered with work(65 patients), walking(56 patients), mood(52 patients), life enjoyment(49 patients), general activity(49 patients), and relationships with other people(42 patients). Medications prescribed for HR-QOL control were non-steroidal anti-inflammatory drugs (93 patients), morphine(32 patients), and adjuvant analgesics(47 patients).

Conclusion:
The present findings may help in the development of management strategies for physical and psychological distress, and improve HR-QOL of cancer outpatients treated with chemotherapy.

Comment on Keeping Up With Science : InTech Publishes 49 New Books For You To Get Hold Of Right Now by sandipniauskas

Comment on Keeping Up With Science : InTech Publishes 49 New Books For You To Get Hold Of Right Now by sandipniauskas:

Thanks on behalf of our ovarian cancer communities, families and friends for your book on Ovarian Cancer and in particular the section by Dr Yi Pan (neuropathy). Yi is a favourite and does so very much for many patients.

press release: Scripps Research scientists provide new understanding of chronic pain (neuropathic pai

(In research)

Findings suggest new target for drug development

LA JOLLA, CA – January 22, 2012 – Millions of people worldwide suffer from a type of chronic pain called neuropathic pain, which is triggered by nerve damage. Precisely how this pain persists has been a mystery, and current treatments are largely ineffective. But a team led by scientists from The Scripps Research Institute, using a new approach known as metabolomics, has now discovered a major clue: dimethylsphingosine (DMS), a small-molecule byproduct of cellular membranes in the nervous system. In their new study, the scientists found that DMS is produced at abnormally high levels in the spinal cords of rats with neuropathic pain and appears to cause pain when injected. The findings suggest inhibiting this molecule may be a fruitful target for drug development.....

American Academy of Neurology issues new guideline on best treatments for diabetic nerve pain (neuropathy)

EvidenceUpdates - Interventions for preventing neuropathy caused by cisplatin and related compounds

BACKGROUND:
Cisplatin and several related antineoplastic agents used to treat many types of solid tumors are neurotoxic, and most patients completing a full course of cisplatin chemotherapy develop a clinically detectable sensory neuropathy. Effective neuroprotective therapies have been sought.


AUTHORS' CONCLUSIONS:
At present, the data are insufficient to conclude that any of the purported chemoprotective agents (acetylcysteine, amifostine, calcium and magnesium, diethyldithiocarbamate, glutathione, Org 2766, oxycarbazepine, or Vitamin E) prevent or limit the neurotoxicity of platin drugs among human patients.

abstract: JCO - Natural History of (Taxol) Paclitaxel-Associated Acute Pain Syndrome: Prospective Cohort Study NCCTG N08C1

Abstract

Purpose The characteristics and natural history of the
paclitaxel–acute pain syndrome (P-APS) and paclitaxel's
more chronic neuropathy have not been well delineated. 

Methods Patients receiving weekly paclitaxel (70 to 90 mg/m²) completed daily questionnaires and weekly European
Organisation for Research and Treatment of Cancer (EORTC) Chemotherapy-Induced Peripheral Neuropathy (CIPN) –20
instruments during the entire course of therapy. 

Results P-APS symptoms peaked 3 days after chemotherapy.
Twenty percent of patients had pain scores of 5 to 10 of 10 with
the first dose of paclitaxel. Sensory neuropathy symptoms wer
e more prominent than were motor or autonomic neuropathy

symptoms. Of the sensory neuropathy symptoms, numbness and
tingling were more prominent than was shooting or burning pain. Patients with higher P-APS pain scores with the first dose of
paclitaxel appeared to have more chronic neuropathy. 

Conclusion These data support that the P-APS is related to nerve pathology as opposed to being arthralgias and/or myalgias.
Numbness and tingling are more prominent chronic neuropathic symptoms than is shooting or burning pain. 

define:  arthralgias: Aches or pains in joints, without obvious
swelling, warmth, or redness.
vasculitis.med.jhu.edu/whatis/glossary.html

define: myalgias:  pain in a muscle or group of muscles
wordnetweb.princeton.edu/perl/webwn

Mayo Clinic - Mayo Clinic Finds Inflammation Causes Some Postsurgical Neuropathies (nerve damage)

Coping with Peripheral Neuropathy : Cancer News

Peripheral neuropathy — Managing the side effects of chemotherapy - MayoClinic.com

focus on: Cancer Neuropathic Pain: Overview of Current Status and Future Objectives -- The Oncologist

 ARTICLES

Cancer Neuropathic Pain: Overview of Current Status and Future Objectives

Frederick H. Hausheer, Kathleen M. Foley
The Oncologist 2010; 15(Supplement 2): 1-2; doi:10.1634/theoncologist.2009-S506
[Full Text] [PDF]  

Types and Epidemiology of Cancer-Related Neuropathic Pain: The Intersection of Cancer Pain and Neuropathic Pain

Mark J. Lema, Kathleen M. Foley, Frederick H. Hausheer
The Oncologist 2010; 15(Supplement 2): 3-8; doi:10.1634/theoncologist.2009-S505
[Abstract] [Full Text] [PDF]   SUMMARY: This article briefly surveys the types and causes of neuropathic pain and then discusses what is known about the epidemiology of cancer-related neuropathic pain.

Pathophysiology and Animal Models of Cancer-Related Painful Peripheral Neuropathy

Gary J. Bennett
The Oncologist 2010; 15(Supplement 2): 9-12; doi:10.1634/theoncologist.2009-S503
[Abstract] [Full Text] [PDF]   SUMMARY: The article reviews some of the work that has been done to study the peripheral causes of neuropathic pain as it relates to cancer.

Assessment of Cancer-Related Neuropathy and Neuropathic Pain

Charles S. Cleeland, John T. Farrar, Frederick H. Hausheer
The Oncologist 2010; 15(Supplement 2): 13-18; doi:10.1634/theoncologist.2009-S501
[Abstract] [Full Text] [PDF]   SUMMARY: This article briefly outlines the currently accepted measures of neuropathy and neuropathic pain, discusses their commonalities and limitations, and offers thoughts on improvements to current assessment strategies.

Integrative and Behavioral Approaches to the Treatment of Cancer-Related Neuropathic Pain

Barrie R. Cassileth, Francis J. Keefe
The Oncologist 2010; 15(Supplement 2): 19-23; doi:10.1634/theoncologist.2009-S504
[Abstract] [Full Text] [PDF]   SUMMARY: This article briefly describes research illustrating the promise of important integrative oncology therapies for the treatment of cancer-related neuropathic pain, including massage therapy, acupuncture, and psychological/behavioral interventions.

Future Directions in Neuropathic Pain Therapy: Closing the Translational Loop

Miroslav Backonja, Clifford J. Woolf
The Oncologist 2010; 15(Supplement 2): 24-29; doi:10.1634/theoncologist.2009-S502
[Abstract] [Full Text] [PDF]   SUMMARY: This article briefly reviews emerging treatments for neuropathic pain and discusses specific opportunities to alter the drug discovery paradigm, stressing the need for an approach that emphasizes the unbiased evaluation of the particular neurobiological mechanisms contributing to neuropathic pain in individual patients.

An open-label, non-randomized comparison of venlafaxine and gabapentin as monotherapy or adjuvant therapy in the management of neuropathic pain in patients with peripheral neuropathy

Note:

*click on 'pdf' to access the full paper (free)
* this paper is not specific to neuropathy as a treatment related adverse effect of cancer therapies
* it is written in fairly easy to understand language
* discusses side effects

Vitamin E neuroprotection for cisplatin neuropathy: A randomized, placebo-controlled trial -- Neurology

Conclusions: This phase III study confirms the neuroprotective role of vitamin E against cisplatin peripheral neurotoxicity. Vitamin E supplementation should be adopted in patients receiving cisplatin-based chemotherapy.

Omega-3 fatty acids for neuropathic pain: case series

CONCLUSIONS: This first-ever reported case series suggests that omega-3 fatty acids may be of benefit in the management of patients with neuropathic pain. Further investigations with randomized controlled trials in a more specific neuropathic pain population would be warranted.