Source: www.healio.com
Author: Jennifer Byrne

For many patients with head and neck cancer, treatment-associated oral mucositis is a source of severe pain. Managing this pain is a priority for physicians and interdisciplinary care teams.

Although opioid painkillers historically have been used for this purpose, researchers at Roswell Park Comprehensive Cancer Center investigated the use of gabapentin, a drug used to alleviate nerve pain, as an alternative to narcotics for this patient population.

“Virtually all patients will require some type of pain relief or analgesic medication during the course of chemotherapy and radiation,” study author Anurag K. Singh, MD, professor of oncology and director of radiation research at Roswell Park, told Healio. “We’ve been studying better ways to improve pain control in this population because standard narcotics just don’t work that well. Patients tend to use a lot and they still experience pain, but they are sleepier.”

A dose-dependent effect
In their study, published in Cancer, Singh and colleagues randomly assigned 60 patients with head and neck squamous cell carcinoma to one of two treatment regimens: high-dose gabapentin (2,700 mg daily), progressing sequentially to hydrocodone-acetaminophen and fentanyl when needed (n = 31), or low-dose gabapentin (900 mg daily) progressing to methadone as needed (n = 29).

Safety and toxicity served as the study’s primary endpoints. Pain, opioid requirement and quality of life served as secondary endpoints.

Results showed no difference in pain between the treatment groups, but more patients in the high-dose gabapentin group did not need an opioid while receiving treatment (42% vs. 7%; P = .002). Patients whose treatment progressed to methadone rather than hydrocodone and fentanyl had significantly better quality-of-life outcomes in terms of general health (P = .05), physical functioning (P = .04) role functioning (P = .01) and social functioning (P = .01).

“The bottom line is there was a dose-dependent effect of gabapentin,” Singh told Healio. “When you go from 7% in the lower-dose arm, or 0% if you weren’t giving gabapentin at all, to 42% in the higher-dose arm, that’s a really obvious difference.”

‘Potential arrow in our quiver’
The team at Roswell Park has begun using gabapentin as a first-line approach to pain for patients with head and neck cancer, Singh said.

“We use even higher-dose gabapentin now. We go up to 3,600 mg and follow it with methadone when needed,” he told Healio. “We’re having excellent results. Currently, we’re studying whether we can add something to the gabapentin to get narcotics even further out of the equation.”

Singh and study first author Gregory Hermann, MD, MPH, resident physician in radiation medicine at Roswell Park, have started to evaluate use of the antidepressant venlafaxine (Effexor, Pfizer), which was shown in a study conducted in Europe to enhance the effects of gabapentin.

“Venlafaxine is an SNRI [serotonin-norepinephrine reuptake inhibitor] that is similar to other drugs like duloxetine (Cymbalta, Eli Lilly) that have been used for neuropathic pain in diabetes. It’s a very common medication that is used in primary care,” Hermann told Healio. “At the end of the study, we’ll be able to say whether 3,600 mg is more effective than 2,700 mg and whether venlafaxine adds anything.”

Although opioid painkillers are known for their addictive potential, opioid abuse is less likely among patients with head and neck cancer, provided they are used properly, according to Heath Skinner, MD, PhD, associate professor of radiation oncology at UPMC Hillman Cancer Center. improve significantly within a few weeks of treatment completion,” Skinner told Healio. “In that situation, the goal is to manage pain to allow for eating and drinking as much as possible. Once the acute event leading to the pain is at least partially resolved, we start to wean those medications down. So, in the acute setting, I think these medications have a very limited addiction potential.”

However, if improperly prescribed for long-term use, opioid painkillers could become addictive, Skinner said. Moreover, narcotic painkillers are associated with significant toxicities for an already sick population.

“Constipation is a common effect with opioids and can be particularly challenging for [patients with head and neck cancer] because they’re not drinking a lot of fluids or eating much food,” Skinner told Healio. “That could exacerbate a problem known to happen with narcotic-based pain medications.”

Skinner said gabapentin is a promising alternative to opioids that is readily accessible to clinicians.

“It’s available in the setting of pain control and easily prescribed,” he said. “It’s not something that’s proprietary that a clinician couldn’t acquire. It’s nice to have another potential arrow in our quiver.” – by Jennifer Byrne

Reference:
Hermann GM, et al. Cancer. 2020;doi:10.1002/cncr.32676,

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