Pain and Chemotherapy

No one class of chemotherapy is more likely than another to cause CIPN.

Pain is a common problem among patients with cancer, and one of the goals of treatment of the disease is pain relief. However, there are times when the therapies for cancer can result in pain, which can be even more severe than the pain caused by the cancer itself.

The etiology of some of the treatment-related pain can be easily recognized. Patients who have undergone surgery for cancer may suffer extended pain at the surgical site. Women who undergo surgery for breast cancer in which there is removal of lymph nodes can have painful lymphedema.

One of the less understood and often unrecognized forms of pain related to cancer therapies is chemotherapy-induced peripheral neuropathy (CIPN). A recently published review of this condition provided useful information on our current state of knowledge regarding this problem.¹

CIPN occurs frequently: According to the literature, almost 48% of adult cancer patients who undergo chemotherapy develop it. The majority of these patients develop it within a month after the end of chemotherapy, and for most it resolves within a few months. However, in 30% of patients, it persists for 6 months or longer.

The study authors sought to determine if there are identifiable risk factors for CIPN that would help us predict which patients are most likely to develop it. Perhaps the most important finding is that no particular class of chemotherapy drug was more likely to cause CIPN over any other, nor was any type of cancer more likely to be associated with CIPN.

The study identified several of what the authors described as risk factors for CIPN, including a baseline neuropathy; a history of smoking; decreased creatinine clearance; and specific sensory changes during chemotherapy such as cold allodynia, where pain occurs in response to usually non-painful cold stimuli, and cold hyperalgesia, where there is exaggerated pain in response to normally cold painful stimuli.

None of these findings are too surprising. We might expect someone with neuropathy to experience an exacerbation of the condition as a result of chemotherapy or to develop further neuropathies. Since allodynia and hyperalgesia are signs of neuropathy, they may actually be considered early indications (as opposed to risk factors) of CIPN. Both smoking and renal problems can affect nerve function.

Four of the studies that were reviewed showed that there were apparent genetic risk factors for CIPN, although the review authors noted that all of the studies had methodology issues that limited their usefulness.

Essentially the bottom line is that for right now our ability to predict who will develop CIPN is virtually nonexistent. This isn’t too surprising since a similar statement can be made about most other neuropathic conditions. We still can’t predict who will develop diabetic peripheral neuropathic pain; postherpetic neuralgia; complex regional pain syndrome (formerly called reflex sympathetic dystrophy); or fibromyalgia, which is now viewed by many experts as a neuropathic condition.

In light of this, it is important to monitor all patients undergoing chemotherapy for CIPN. Considering that chemotherapy can cause so many other major problems, such as fever, nausea and vomiting, loss of appetite, fatigue, and hair loss, it is understandable that CIPN may be overlooked unless healthcare providers are watching for its presence.

Whether or not early identification of CIPN makes a difference in outcome is still an open question. As previously noted, we still don’t understand the underlying pathophysiologic mechanisms that result in CIPN, so whether it is possible to make an early intervention that may limit its progression is unknown.

As with most forms of neuropathic pain, CIPN can be difficult to treat. The drugs that are usually most efficacious for neuropathic pain, antiepileptics and serotonin-norepinephrine reuptake inhibitors (SNRIs), have generally been found to provide limited analgesia for CIPN, although a paper published last year reported that duloxetine (Cymbalta), an SNRI that is FDA-approved for the pain of diabetic peripheral neuropathy and fibromyalgia, provided significantly more relief than placebo.² However, the study was only for 5 weeks, a very short amount of time for many with CIPN.

References:

1. Seretny M, Currie GL, Sena ES, et al. Incidence, prevalence, and predictors of chemotherapy-induced peripheral neuropathy: A systematic review and meta-analysis. Pain. 2014;155:2461-2470. http://www.painjournalonline.com/article/S0304-3959%2814%2900443-6/abstract

2. Smith EM, Pang H, Cirrincione C, et al. Effect of duloxetine on pain, function, and quality of life among patients with chemotherapy-induced painful peripheral neuropathy: a randomized clinical trial. JAMA. 2013;309:1359-1367. http://jama.jamanetwork.com/article.aspx?articleid=1674238