Effects on Chemo Induced Neuropathy

ONE OF THE KEY INGREDIENTS IN CRYODERM
REVERSES CHEMOTHERAPY-INDUCED
PERIPHERAL NEUROPATHY AND ENABLES FURTHER EFFECTIVE CHEMOTHERAPY DELIVERY.



Multiple case reports have been published recently describing the revolutionary discovery that will help alleviate severe chemotherapy-induced peripheral neuropathy and to allow further life-prolonging chemotherapy.

Chemotherapy-induced peripheral neuropathy can be a major dose-limiting side effect and leave some cancer patients with long-term pain and functional disability. In some cases, the neuropathy can be so severe as to preclude further life-prolonging chemotherapy.

Case 1

In the article, Storey and co-workers (Edinburgh Cancer Research UK Centre, University of Edinburgh, United Kingdom) report a case of painful, carboplatin-induced peripheral neuropathy in a 71-yearold woman with a four and a half year history of Stage 4 epithelial ovarian cancer.

The woman presented with Grade 3 neurosensory toxicity and complaints of paresthesias, pain, weakness in her hands and difficulty with motor tasks. Amitriptyline 10 mg nightly helped the pain slightly, but she did not tolerate an increased dose of 25 mg.

Her CA-125(marker for ovarian cancer recurrence) was increasing again, but it was felt that her Grade 3 peripheral neuropathy would likely preclude her from further life-saving platinum or taxane therapy.


The authors treated her with topical application of the CRYODERM's® active ingredient applied over the upper extremities and the skin overlying the corresponding nerve roots. Detailed pain assessment was performed before the treatment, with further assessments 90 minutes after the application, then 2, 6, 10, and15 weeks later.

Results:

There was decreased pain in response to suprathreshold stimulus. The patient continued the treatment twice daily, and these changes were maintained at 2 weeks when she also reported less pain and improved function. By six weeks, the mechanical detection and pain thresholds had improved, and the area of abnormal sensation to light touch, cool, and warm stimuli had markedly decreased. By 10 weeks, her total Brief Pain Inventory score reduced from 31 to 10, and by 15 weeks, she was able to fasten buttons, undo jewelry clasps, and was no longer dropping things. When treatment was continued during chemotherapy, the peripheral neuropathy did not deteriorate.

Case 2

Colvin et al (Centre for Neuroscience Research, Departments of Hematology, Edinburgh, Scotland) report a case of severe bortezomib-induced neuropathy in a 69-year-old man with a 39-month history of multiple myeloma. After his disease relapsed, bortezomib was commenced as third-line antimyeloma treatment. Unfortunately, after two cycles of bortezomib, the patient complained of paresthesias, numbness, and “lightning-like” pains in both hands, which did not resolve despite a 50% dose reduction for the third cycle.

A month later, he developed an extremely painful peripheral neuropathy (grade 4) in his lower limbs. The predominant feature was severe burning, with significant sleep disturbance, high levels of distress, and reduced general function, such that he was virtually bed-bound. Bortezomib was therefore discontinued.

Treatment for neuropathic pain with traditional systemic agents was limited by significant adverse effects.

The patient was treated with CRYODERM's® active ingredient topically. It was applied to the lower limbs and to the skin over the lumbosacral region of the spine corresponding with the affected nerve roots, with a detailed pain assessment before the treatment, 90 minutes after treatment, and then 2 weeks later.

Results:

Profound changes in Quantitative Sensory Testing were detected 90 minutes after treatment. There was a marked increase in mechanical pain threshold with decreased pain in response to suprathreshold stimulus (VAS score changed from 8 to 2 for both right and left side) and complete reversal of wind-up (VAS reduced from 8 to 0). The patient was able to walk without a stick for the first time since the lower limb neuropathy started. These changes were consistently maintained at the 2-week assessment. The patient continued the treatment twice daily. After 5 days, he reported a sustained improvement in pain control, sleep, mobility, general function, and mood. This was maintained at 2 weeks with his total Brief Pain Inventory score reduced from 56 to 14 and his Hospital Anxiety and Depression scores reduced from 22 to 16. His hand symptoms, which were not treated, remained unchanged, suggesting no spontaneous resolution of his neuropathy.

Conclusions:

Effective treatment of chemotherapy-induced neuropathy with one of CRYODERM's® key active ingredients allowed continued life-prolonging treatment with good clinical response and no adverse effect!

References:

  • Dawn J. Storey BMedSci, BMBS, MD, Lesley A. Colvin BSc (Hons), MBChB, PhD, Melanie J. Mackean MBChB, MD, Rory Mitchell PhD, Susan M. Fleetwood-Walker PhD and Marie T. Fallon MBChB, MD. Reversal of Dose-Limiting Carboplatin-Induced Peripheral Neuropathy with TRPM8 Activator, Menthol, Enables Further Effective Chemotherapy Delivery. Journal of Pain and Symptom Management. Volume 39, Issue 6, June 2010, Pages e2-e4.
  • Proudfoot CJ, Garry EM, Cottrell DF, et al. Analgesia mediated by the TRPM8 cold receptor in chronic neuropathic pain. Curr Biol 2006; 16: 1591e1605.
  • Colvin LA, Johnson PRE, Mitchell R, Fleetwood-Walker SM, Fallon MT. From bench to bedside: a case of rapid reversal of bortezomib-induced neuropathic pain by the TRPM8 activator, Menthol. J Clin Oncol 2008; 26:4519e4520.