New Guidelines on Chemotherapy-Induced Peripheral Neuropathy
New Guidelines on Chemotherapy-Induced Peripheral Neuropathy
Medscape: What were the recommendations for the treatment of CIPN?
Dr. Hershman: The drug with the strongest support for use in the treatment of CIPN is duloxetine. A randomized, placebo-controlled trial showed benefit of duloxetine in reducing pain from neuropathy. Only one study has been done to look at duloxetine, and it was underpowered to examine differences according to the chemotherapy agent (eg, oxaliplatin vs a taxane), so there are still some unanswered questions about duloxetine. One of those questions is its long-term tolerability, because this was a short-term study and the medication was associated with some side effects. The recommendation to use duloxetine was moderate.
Several other drugs have had conflicting results or have shown significant benefits in the neurologic literature. Some of the clinical trials that have been done were quite small and the outcome measures may not have been perfect. Nevertheless, these agents deserve continued study. Given the fact that CIPN can be a life-altering side effect of chemotherapy, our suggestion is that it is not unreasonable to at least try these agents to see whether there is some improvement on a patient-by-patient basis. These agents include: (1) a tricyclic antidepressant such as nortriptyline; (2) gabapentin and drugs with a similar mechanism of action; and (3) compounded topical gel containing baclofen, amitriptyline HCl, and ketamine. There is a moderate recommendation against using lamotrigine.
Medscape: The guidelines include a section on communicating with patients. What are some of the most important subjects to discuss?
Dr. Hershman: It's important for patients to be aware that they should let their physicians know as soon as they start to experience numbness, tingling, or pain. There may be other cancer treatment options that are equally efficacious, and the clinician may choose to change treatment. If not, there can be a discussion about the potential risks and benefits of the treatment that the patient is receiving. It's also important to discuss risks and benefits of medications or supplements that patients can obtain without a prescription. ALC is a case in point; it is available over the counter, so many patients may be unaware that it can be harmful.
Medscape: What is the next step in finding effective preventive or treatment approaches for CIPN?
Dr. Hershman: It would be better if our guidelines showed that many more agents were useful in the treatment and prevention of CIPN. The most important result of our work is that it really opens our eyes to the fact that although a considerable amount of research has been done, we still don't have good options for CIPN. To get to the next stage, we need a better understanding of the causative mechanism of CIPN and the reasons why some patients are more susceptible to CIPN than others. This may allow physicians to better personalize treatments based on risks of toxicity. If we have a better understanding of the mechanism, we may also figure out factors that might make it worse and that are important to avoid. These guidelines bring to the forefront the evidence that is available. Many physicians use agents that have no efficacy, so it's important that we communicate what people should be avoiding in terms of treating CIPN.
Medscape: In view of the paucity of high-quality data, should clinicians talk to their patients about possible participation in clinical trials?
Dr. Hershman: Absolutely. The only way that we will move this field forward is with more research. Some of the studies have been fairly surprising. ALC is an example; preclinical data and phase 2 data suggested a benefit, but when you do the more definitive, larger, placebo-controlled study, you see that it actually might make things worse. Without that evidence, we could be doing harm. It's very important that we think about new options for patients, but we must study them in a rigorous way so that we know that what we offer our patients isn't actually hurting them. That is the message to get across: that we have a lot more work to do, and we should be careful about giving drugs or supplements without studying them.
Little to Offer for Treatment
Medscape: What were the recommendations for the treatment of CIPN?
Dr. Hershman: The drug with the strongest support for use in the treatment of CIPN is duloxetine. A randomized, placebo-controlled trial showed benefit of duloxetine in reducing pain from neuropathy. Only one study has been done to look at duloxetine, and it was underpowered to examine differences according to the chemotherapy agent (eg, oxaliplatin vs a taxane), so there are still some unanswered questions about duloxetine. One of those questions is its long-term tolerability, because this was a short-term study and the medication was associated with some side effects. The recommendation to use duloxetine was moderate.
Several other drugs have had conflicting results or have shown significant benefits in the neurologic literature. Some of the clinical trials that have been done were quite small and the outcome measures may not have been perfect. Nevertheless, these agents deserve continued study. Given the fact that CIPN can be a life-altering side effect of chemotherapy, our suggestion is that it is not unreasonable to at least try these agents to see whether there is some improvement on a patient-by-patient basis. These agents include: (1) a tricyclic antidepressant such as nortriptyline; (2) gabapentin and drugs with a similar mechanism of action; and (3) compounded topical gel containing baclofen, amitriptyline HCl, and ketamine. There is a moderate recommendation against using lamotrigine.
Medscape: The guidelines include a section on communicating with patients. What are some of the most important subjects to discuss?
Dr. Hershman: It's important for patients to be aware that they should let their physicians know as soon as they start to experience numbness, tingling, or pain. There may be other cancer treatment options that are equally efficacious, and the clinician may choose to change treatment. If not, there can be a discussion about the potential risks and benefits of the treatment that the patient is receiving. It's also important to discuss risks and benefits of medications or supplements that patients can obtain without a prescription. ALC is a case in point; it is available over the counter, so many patients may be unaware that it can be harmful.
Medscape: What is the next step in finding effective preventive or treatment approaches for CIPN?
Dr. Hershman: It would be better if our guidelines showed that many more agents were useful in the treatment and prevention of CIPN. The most important result of our work is that it really opens our eyes to the fact that although a considerable amount of research has been done, we still don't have good options for CIPN. To get to the next stage, we need a better understanding of the causative mechanism of CIPN and the reasons why some patients are more susceptible to CIPN than others. This may allow physicians to better personalize treatments based on risks of toxicity. If we have a better understanding of the mechanism, we may also figure out factors that might make it worse and that are important to avoid. These guidelines bring to the forefront the evidence that is available. Many physicians use agents that have no efficacy, so it's important that we communicate what people should be avoiding in terms of treating CIPN.
Medscape: In view of the paucity of high-quality data, should clinicians talk to their patients about possible participation in clinical trials?
Dr. Hershman: Absolutely. The only way that we will move this field forward is with more research. Some of the studies have been fairly surprising. ALC is an example; preclinical data and phase 2 data suggested a benefit, but when you do the more definitive, larger, placebo-controlled study, you see that it actually might make things worse. Without that evidence, we could be doing harm. It's very important that we think about new options for patients, but we must study them in a rigorous way so that we know that what we offer our patients isn't actually hurting them. That is the message to get across: that we have a lot more work to do, and we should be careful about giving drugs or supplements without studying them.
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