Paclitaxel is an effective chemotherapeutic agent that is widely used for the treatment of several cancers, including breast and ovarium cancer. However, it induces disabling and potentially long-lasting sensory neuropathy. 

Paclitaxel and long-lasting sensory neuropathy

Paclitaxel is known for inducing painful Chemotherapy-induced peripheral neuropathy (CIPN).

41338699-Palto-Dreamstime-INP Paclitaxel neuropathyChemotherapy-induced peripheral neuropathy in general presents as disturbances in motor, sensory, and autonomic function. It leads to a glove and stocking distribution due to preferential effects on sensitive longer axons.

Immune processes and neuro inflammation are linked to its pathogenesis.[Starbova, H., Vetter, I. Pathophysiology of chemotherapy-induced peripheral neuropathy. Frontiers in molecular neuroscience, 2017, 10: 174.]In a significant number of cases it leads to irreversible neuropathic pain.

How often does Paclitaxel lead to neuropathy?

How often Paclitaxel leads to a painful and irreversible Chemotherapy-induced peripheral neuropathy (CIPN)? That is an important question to answer.

Especially since many oncologists tend to think CIPN resolves in most patients treated with chemotherapy.

In our clinic we frequently see patients, who have been treated in the past with a number of chemotherapeutic cocktails, with a chronic painful axonal neuropathy. The neuropathy and its pain symptoms occurred during or shortly after chemotherapy.

Its mechanism of action is probably related to axonal transport defects leading to axonal degeneration.[Gornstein E, Schwarz TL. The paradox of Paclitaxel neurotoxicity: Mechanisms and unanswered questions. Neuropharmacology, 2014, 76: 175-183.] In order to explore the topic of the emergence of this painful CIPN: 28 patients with early-stage breast cancer treated with Paclitaxel were followed. Nearly 3/4 of all patients developed neuropathic symptoms by 6 weeks of treatment.

This neuropathy was not self limiting. The majority of patients (63%) did not experience recovery of neuropathic symptoms at follow-up. Clearly Paclitaxel produces early sensory dysfunction and leads to persistent neuropathy.

The authors stated the possibility to avoid this nasty neuropathy based on neuroprotective strategies:

  • significant axonal dysfunction within the first month of treatment predated symptom onset, suggesting a window for neuroprotective therapies. [1]

Our Institute for Neuropathic Pain (INP)

We developed a protocol for treating such pain, based on analgesic and neuroprotective elements. This protocol is based on the application of the analgesic and neuroprotective cream base on 10% phenytoin. And the intake of 3 times 400 mg capsules containing the anti-inflammatory and analgesic autacoid Palmitoylethanolamide (PEA).

In the past we have reported various cases, where neuropathic pain could be treated with these new therapeutic inroads.

That is why it is important to note that researchers from the department of Pharmacology and Toxicology of the Virginia Commonwealth University, Richmond (USA), together with the Palmitoylethanolamide (PEA) experts from the Department of Biotechnology and Bioscience from the University of Milano-Bicocca, Milan, Italy explored its anti-allodynic effects in a special mouse model.

References

Park, SB,  Lin, C. S. Y., Krishnan, A. V., Friedlander, M. L., Lewis, C. R., & Kiernan, M. C., Early, progressive, and sustained dysfunction of sensory axons underlies Paclitaxel‐induced neuropathy. Muscle & nerve, 2011, 43.3: 367-374.

December 2010, Jan M. Keppel Hesselink, MD, PhD
‘Paclitaxel and long-lasting sensory neuropathy’

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Referentielijst

[1] Park SB, Lin CS, Krishnan AV, Friedlander ML, Lewis CR, Kiernan MC. | Early, progressive, and sustained dysfunction of sensory axons underlies paclitaxel-induced neuropathy. | Muscle Nerve. | 2010 Dec 9. [Epub ahead of print]


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