BACKGROUND: Chemotherapy-induced peripheral neuropathy (CIPN) is a commonly encountered disease entity following chemotherapy for cancer treatment. Although only duloxetine is recommended by the American Society of Clinical Oncology (ASCO) for the treatment of CIPN in 2014, the evidence of the clinical outcome for new pharmaceutic therapies and non-pharmaceutic treatments has not been clearly determined.
OBJECTIVE: To provide a comprehensive review and evidence-based recommendations on the treatment of CIPN.
STUDY DESIGN: A systematic review of each treatment regimen in patients with CIPN.
METHODS: The literature on the treatment of CIPN published from 1990 to 2017 was searched and reviewed. The 2011 American Academy of Neurology Clinical Practice Guidelines Process Manual was used to grade the evidence and risk of bias. We reviewed and updated the recommendations of the ASCO in 2014, and evaluated new approaches for treating CIPN.
RESULTS: A total of 26 treatment options in 35 studies were identified. Among these, 7 successful RCTs, 6 failed RCTs, 18 prospective studies, and 4 retrospective studies were included. The included studies examined not only pharmacologic therapy but also other modalities, including laser therapy, scrambler therapy, magnetic field therapy and acupuncture, etc. Most of the included studies had small sample sizes, and short follow-up periods. Primary outcome measures were highly variable across the included studies. No studies were prematurely closed owing to its adverse effects.
LIMITATIONS: The limitations of this systematic review included relatively poor homogeneous, with variations in timing of treatment, primary outcomes, and chemotherapeutic agents used.
CONCLUSION: The evidence is considered of moderate benefit for duloxetine. Photobiomodulation, known as low level laser therapy, is considered of moderate benefit based on the evidence review. Evidence did not support the use of lamotrigine and topical KA (4% ketamine and 2% amitriptyline). The evidence for tricyclic antidepressants was inconclusive as amitriptyline showed no benefit but nortriptyline had insufficient evidence. Further research on CIPN treatment is needed with larger sample sizes, long-term follow-up, standardized outcome measurements, and standardized treatment timing.
KEY WORDS: Chemotherapy-induced neuropathy, peripheral neuropathy, chemotherapy-tumor, neuropathic pain, chronic pain, toxicology, treatment, reduction of pain, level of evidence.
This was a very well done review. The lack of data for most interventions was eye opening. I did not know about PBM and this added another treatment to think about. It also helped push me to use duloxetine more frequently.
These results are somewhat expected given the data (or lack thereof) for other peripheral neuropathies. Overall, insufficient evidence is available despite very broad search criteria, including all study types - randomized, nonrandomized and observational. Only 4 modalities had adequate evidence to draw any conclusion. Duloxetine and photobiomodulation both demonstrate a moderate benefit and evidence supports the lowest level of recommendation. However, lamotrogine and topical ketamine/amitriptyline should not be offered because of lack of benefit. The data are insufficient for all other interventions. High quality randomized controlled trials are necessary to conclusively recommend treatments for chemotherapy-induced neuropathy.
An important insight on the treatment of a challenging toxicity that is really common in our daily practice. It supports what we are prescribing and diminishes the will to use amitryptiline.
As an Oncologist, I thought it was important to see an update on this issue (CIPN). The conclusions were not very newsworthy in the sense that it will be hard to challenge ASCO's recommendations to use Duloxetine for CINP. However, some interesting points were made that may help to standardize future clinical trials on this matter. I found the review was, if anything, a bit too inclusive as the designated "class IV trials" should not, in my view have been included.