Chemotherapy Neuropathy – Prevent and Treament

Use of agents to reduce chemotherapy induced peripheral neuropathy confounded by issues of decreased anti-cancer effectiveness. L-Acetyl Carnitine during chemotherapy, and Venlafaxine or Duloxetine after are my choices.  Tricyclics, gabapentin, lyrica, and topical agents did not rate well and belie the idea neuropathy can be treated as a”group” process.

Am J Health Syst Pharm. 2014 Jan 1;71(1):19-25.
Prevention and treatment of chemotherapy-induced peripheral neuropathy.
Piccolo J, Kolesar JM.
http://www.ncbi.nlm.nih.gov/pubmed/24352178

  • 30-40% of cancer chemotherapy patients get frank peripheral neuropathy and 70 % get some features of.
  • Agents include platinum compounds, taxanes, vinca alkaloids, thalidomide, lenalidomide, bortezomib, and ixabepilone
  • symptoms – paresthesia funny feelings, numbness, tingling and burning, skin hypersensitivity, loss of tendon reflexes (especially achilles), loss of vibration and propioception in fingers and toes up.
  • Aggravating issues – alcoholism, diabetes and from my one cases – low B12

Prevention – one agent found to be cardiotoxic so only safe agents will be discussed. Concerns are, that use of helpful agents could reduce therapeutic effectiveness.  Omega 3 was supposed to be a helpful agent and yet now implicated in increased in prostate cancer risk:
Plasma Phospholipid Fatty Acids and Prostate Cancer Risk in the SELECT Trial
Theodore M. Brasky, Amy K. Darke, Xiaoling Song, Catherine M. Tangen, Phyllis J. Goodman, Ian M. Thompson, Frank L. Meyskens Jr, Gary E. Goodman, Lori M. Minasian, Howard L. Parnes, Eric A. Klein and Alan R. Kristal
JNCI J Natl Cancer Inst (2013) 105 (15): 1132-1141.
http://jnci.oxfordjournals.org/content/105/15/1132.short

PREVENTION:

One of the most effective agents in prevention of  Chemotherapy induced neuropathy is magnesium and calcium intravenous:
Beijers, A. J., J. L. Jongen, and G. Vreugdenhil.
Chemotherapy-induced neurotoxicity: the value of neuroprotective strategies. Neth J Med 70, no. 1 (2012): 18-25.
http://www.njmonline.nl/getpdf.php?t=a&id=10000794

  • However, anti-cancer response rates were 32.9% in placebo and 17.3% on IV magnsium/calcium though worked well for neuropathy prevention.
  • Though contradicted by one later analysis – this will never see the light of day.
  • What was not mentioned was fact IV magnesium might have benefits AFTERWARDS – I wrote a blog note of using magnesium in Complex Regional Pain:
    New Hope For Complex Regional Pain Syndrome I – 5 days Magnesium Infusions       http://painmuse.org/?p=186
  • why not use once anti-cancer effects have been achieved?

Acetyl-L-Carnitine 

  • decreased sensory neuropathy by 60% and motor neuropathy by 79% … in small trial of 25 patients receiving cisplatin and paclitaxel
  • brushed over quickly in this review article but huge amount of evidence of its protective effects on mitochondria that seemed simply ignored by article. I have gotten this agent for cancer patient to use and have written about it here:
    Prevent Chemotherapy Neuropathy With L-Acetyl Carnitine (LAC) – Please Take
    http://painmuse.org/?p=2748
  • There was no evidence it affected cancer drug effectiveness.

Venlafaxine

  • Effects oxidative stress
  • venlafaxine 50 mg quick release prior and 37.5 mg extended release bid over 11 day course chemotherapy – this is a small dose compared to the 150 mg + used for depression treatment.
  • placebo – 38.5% neuropathy versus none in venlafaxine
  • grade 3 neurotoxicity – 33.3% placebo versus none in venlafaxine
  • side effects – first does nausea with quick release – suggested start earlier and stick to sustained release
  • “lingering concerns over the impairment of antitumor activity of chemotherapy”

——————————

TREATMENT

Opioids – and don’t forget methadone

Duloxetine

  • starting at 30 mg and increasing to 60 mg
  • resulted in VAS drop of 1.06 versus 0.34 in placebo – considering that a drop of 1-2 is usually required for clinical effectiveness – this doesn’t reach that – the only way they reached good clinical significance is having a big, I presume drug company sponsored (they did supply the pills), study
    Smith EM, Pang H, Cirrincione C et al.
    Effect of duloxetine on pain function, and quality of life among patients with chemotherapy-induced peripheral neuropathy: a randomized clinical trial.
    JAMA. 2013; 309(13):1359-67.
    http://www.ncbi.nlm.nih.gov/pubmed/23549581
  • A commentary of this study was not complementary – it felt -“The overall strength of effect underpinning this conclusion, however, is relatively small, despite reaching statistical significance. The authors most clearly demonstrated this in Figure 2 in the article, which shows closely approximated or overlapping confidence intervals in both the initial and crossover treatment periods… Small effects, which are difficult to interpret clinically, are a common problem in pain studies.”JAMA. 2013 Aug 7;310(5):537-8. doi: 10.1001/jama.2013.7902.
    Therapy for chemotherapy-induced peripheral neuropathy.
    Seretny M, Colvin L, Fallon M.
    http://www.ncbi.nlm.nih.gov/pubmed/23925630
  •  the rebuttal to that remark agreed the response was “modest” but there are a subgroup of responders that should not be ignored..
  • so statistically significant because they made the study big enough –  but not clinically significant overall – but still worth a try for subgroup responders.

Venlafaxine:
there was a small (13 cases) breast cancer post chemotherapy pain:

Venlafaxine in neuropathic pain following treatment of breast cancer
Tiina Tasmuth, Brita Härtel, Eija Kalso
European Journal of Pain Volume 6, Issue 1, pages 17–24, January 2002
http://onlinelibrary.wiley.com/doi/10.1053/eujp.2001.0266/abstract;jsessionid=2701EEB13387EEF4C17F8344226C9CDC.f04t03?deniedAccessCustomisedMessage=&userIsAuthenticated=false

they found modest effect: -“The average daily pain intensity as reported in the diary (primary outcome) was not significantly reduced by venlafaxine compared with placebo. However, the average pain relief (diary) and the maximum pain intensity (retrospective assessment by the computer program) were significantly lower with venlafaxine compared with placebo.”

but again there is a subgroup of responders:

“The two poor responders had low venlafaxine concentrations whereas the two slow hydroxylizers had high venlafaxine concentrations and excellent pain relief.”

the venlafaxine is great in post breast cancer cases and in certain prostate cancer cases where it is used to control flushes without evidence of worsening the cancer.

 

Comment – all cancer chemotherapy patients need their B12 levels checked beforehand. L-acetyl carnitine should be offered to all chemotherapy patients.  Venlafaxine and IV magnsium should be offered to all post chemotherapy patients. Duloxetine could be offered to non-responders. Opioids should be offered to all. Not mentioned are tricylic antidepressants, topical agents, gabapentin, and pregabalin (lyrica) because of lack of efficacy.. huarache femme huarache femme

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