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 This is an original JCO publication from 2014. Please visit the JCO website to access the full article.


Prevention and Management of Chemotherapy-Induced Peripheral Neuropathy in Survivors of Adult Cancers: American Society of Clinical Oncology Clinical Practice Guideline



 Authors

Dawn L. Hershman, Christina Lacchetti, Robert H. Dworkin, Ellen M. Lavoie Smith, Jonathan Bleeker, Guido Cavaletti, Cynthia Chauhan, Patrick Gavin, Antoinette Lavino, Maryam B. Lustberg, Judith Paice, Bryan Schneider, Mary Lou Smith, Tom Smith, Shelby Terstriep, Nina Wagner-Johnston, Kate Bak, and Charles L. Loprinzi.

THE BOTTOM LINE

 

 

Guideline Question

What are the optimum prevention and treatment approaches in the management of chemotherapy-induced neuropathies in adult cancer survivors?

Target Population

Adult cancer survivors with chemotherapy-induced neuropathies.

 

Target Audience

Health care practitioners who provide care to cancer survivors. 

 

Recommendations

The following recommendations are evidence-based, informed by small RCTs, and guided by clinical experience.  The recommendations were developed by a multi-disciplinary group of experts.  Ratings for benefits, harms, evidence quality and recommendation strength are provided in Table 4 (see Appendix I for rating definitions).

Prevention of Chemotherapy-induced peripheral neuropathy:

There are no established agents recommended for the prevention of CIPN in cancer patients undergoing treatment with neurotoxic agents.   This is based on the paucity of high-quality, consistent evidence and a balance of benefits versus harms.

Clinicians should not offer the following agents for the prevention of CIPN to cancer patients undergoing treatment with neurotoxic agents:

  • acetyl-L-carnitine (ALC)
  • amifostine
  • amitriptyline
  • CaMg for patients receiving oxaliplatin-based chemotherapy
  • diethyldithio-carbamate (DDTC)
  • glutathione (GSH) for patients receiving paclitaxel/carboplatin chemotherapy
  • nimodipine
  • Org 2766
  • all-trans retinoic acid
  • rhuLIF
  • vitamin E

 

Venlafaxine is not recommended for routine use in clinical practice.  While the venlafaxine data supports its potential utility, the data were not strong enough to recommend its use in clinical practice, until additional supporting data become available.

No recommendations can be made on the use of N-acetylcysteine, carbamazepine, glutamate, glutathione for patients receiving cisplatin or oxaliplatin-based chemotherapy, goshajinkigan (GJG), omega-3 fatty acids, or oxycarbazepine for the prevention of CIPN at this time.

Treatment of Chemotherapy-induced peripheral neuropathy

For cancer patients experiencing CIPN, clinicians may offer duloxetine.

 

No recommendations can be made on the use of:

  • Acetyl-L-carnitine, noting that a positive phase III abstract supported its value, but this work has not yet been published in a peer-reviewed journal and a prevention trial suggested that this agent was associated with worse outcomes.
  • Tricyclic antidepressants; however, based on the limited options that are available for this prominent clinical problem and the demonstrated efficacy of these drugs for other neuropathic pain conditions, it is reasonable to try a tricyclic antidepressant (e.g., nortriptyline or desipramine) in patients suffering from CIPN following a discussion with the patients about the limited scientific evidence for CIPN, potential harms, benefits, cost, and patient preferences. 
  • Gabapentin, noting that the available data were limited regarding its efficacy for treating CIPN. However, the panel felt that this agent is reasonable to try for selected patients with CIPN pain given that only a single negative randomized trial for this agent was completed, given the established efficacy of gabapentin and pregabalin for other forms of neuropathic pain, and given the limited CIPN treatment options.  Patients should be informed about the limited scientific evidence for CIPN, potential harms, benefits, and costs.  
  • A topical gel treatment containing baclofen (10 mg), amitriptyline HCL (40 mg), and ketamine (20 mg), noting that a single trial supported that this product did decrease CIPN symptoms.  Given the available data, the panel felt that this agent is reasonable to try for selected patients with CIPN pain.  Patients should be informed about the limited scientific evidence for the treatment of CIPN, potential harms, benefits, and costs.  

 

Note: The guide for rating recommendations and strength of evidence is provided in Appendix I.

 

 

SUMMARY OF RECOMMENDATIONS

 

 

Prevention and treatment approaches in the management of chemotherapy-induced neuropathies in adult cancer survivors

What are the optimum prevention approaches in the management of chemotherapy-induced neuropathies

in adult cancer survivors?

Recommendation

Evidence Rating

There are no established agents recommended for the prevention of CIPN in cancer patients undergoing treatment with neurotoxic agents.   This is based on the paucity of high-quality, consistent evidence and a balance of benefits versus harms.

Type: Evidence-based

Harms outweigh benefits

Evidence quality:  Ranges from low to high

Strength of Recommendation: Ranges from inconclusive to strong against

 

 

Clinicians should not offer the following agents for the prevention of CIPN to cancer patients undergoing treatment with neurotoxic agents:

  • acetyl-L-carnitine (ALC)
  • amifostine
  • amitriptyline
  • CaMg for patients receiving oxaliplatin-based chemotherapy
  • diethyldithio-carbamate (DDTC)
  • glutathione (GSH) for patients receiving paclitaxel/carboplatin chemotherapy
  • nimodipine
  • Org 2766
  • all-trans retinoic acid
  • rhuLIF
  • vitamin E

Venlafaxine is not recommended for routine use in clinical practice.  While the venlafaxine data supports its potential utility, the data were not strong enough to recommend its use in clinical practice, until additional supporting data become available.

 

Type:  Evidence-based

Balance of benefits and harms

Evidence quality: Intermediate

Strength of Recommendation: Inconclusive

 

 

No recommendations can be made on the use of N-acetylcysteine, carbamazepine, glutamate, glutathione for patients receiving cisplatin or oxaliplatin-based chemotherapy, goshajinkigan (GJG), omega-3 fatty acids, or oxycarbazepine for the prevention of CIPN at this time.

 

Type: Evidence-based

Balance of benefits and harms

Evidence quality:  Low

Strength of recommendation: Inconclusive

 

What are the optimum treatment approaches in the management of chemotherapy-induced neuropathies

in adult cancer survivors?

Recommendation

Evidence Rating

For cancer patients experiencing CIPN, clinicians may offer duloxetine.

Type: Evidence-based

Benefits outweigh harms

Evidence quality: Intermediate

Strength of Recommendation: Moderate

No recommendations can be made on the use of acetyl-L-carnitine, noting that a positive phase III abstract supported its value, but this work has not yet been published in a peer-reviewed journal and a prevention trial suggested that this agent was associated with worse outcomes.

Type: Evidence-based

Harms outweigh benefits

Evidence quality:  Low

Strength of Recommendation: Inconclusive

No recommendations can be made on the use of tricyclic antidepressants.  However, based on the limited options that are available for this prominent clinical problem and the demonstrated efficacy of these drugs for other neuropathic pain conditions, it is reasonable to try a tricyclic antidepressant (e.g., nortriptyline or desipramine) in patients suffering from CIPN following a discussion with the patients about the limited scientific evidence for CIPN, potential harms, benefits, cost, and patient preferences. 

Type: Evidence-based

Balance of benefits and harms

Evidence quality: Intermediate

Strength of Recommendation: Inconclusive

No recommendations can be made on the use of gabapentin, noting that the available data were limited regarding its efficacy for treating CIPN. However, the panel felt that this agent is reasonable to try for selected patients with CIPN pain given that only a single negative randomized trial for this agent was completed, given the established efficacy of gabapentin and pregabalin for other forms of neuropathic pain, and given the limited CIPN treatment options.  Patients should be informed about the limited scientific evidence for CIPN, potential harms, benefits, and costs.  

 

Type: Evidence-based

Balance of benefits and harms

Evidence quality: Intermediate

Strength of Recommendation: Inconclusive

No recommendations can be made on the use of a topical gel treatment containing baclofen (10 mg), amitriptyline HCL (40 mg), and ketamine (20 mg), noting that a single trial supported that this product did decrease CIPN symptoms.  Given the available data, the panel felt that this agent is reasonable to try for selected patients with CIPN pain.  Patients should be informed about the limited scientific evidence for the treatment of CIPN, potential harms, benefits, and costs.

Type: Evidence-based

Benefits outweigh harms

Evidence quality: Intermediate

Strength of Recommendation: Inconclusive

 

 

 ASCO Guideline Disclaimer: The clinical practice guidelines and other guidance published herein are provided by the American Society of Clinical Oncology, Inc. ("ASCO") to assist practitioners in clinical decision making. The information therein should not be relied upon as being complete or accurate, nor should it be considered as inclusive of all proper treatments or methods of care or as a statement of the standard of care. With the rapid development of scientific knowledge, new evidence may emerge between the time information is developed and when it is published or read. The information is not continually updated and may not reflect the most recent evidence. The information addresses only the topics specifically identified therein and is not applicable to other interventions, diseases, or stages of diseases. This information does not mandate any particular course of medical care. Further, the information is not intended to substitute for the independent professional judgment of the treating physician, as the information does not account for individual variation among patients. Recommendations reflect high, moderate or low confidence that the recommendation reflects the net effect of a given course of action. The use of words like "must," "must not," "should," and "should not" indicate that a course of action is recommended or not recommended for either most or many patients, but there is latitude for the treating physician to select other courses of action in individual cases. In all cases, the selected course of action should be considered by the treating physician in the context of treating the individual patient. Use of the information is voluntary. ASCO provides this information on an "as is" basis, and makes no warranty, express or implied, regarding the information. ASCO specifically disclaims any warranties of merchantability or fitness for a particular use or purpose. ASCO assumes no responsibility for any injury or damage to persons or property arising out of or related to any use of this information or for any errors or omissions.


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