Pain Treatment for Head and Neck Cancers

While many cancers of the head and neck — mouth, throat and voice box — can be treated successfully, the therapy may come with a major downside: pain. How best to manage it is the focus of a new national clinical trial that is open within the Froedtert & the Medical College of Wisconsin Cancer Network. The HOPE study is comparing usual measures used to alleviate pain to gabapentin, a common drug used to treat nerve-related pain. 

“Receiving radiation therapy for head and neck cancer is like getting a sunburn in the areas where the radiation is aimed,” said Monica Shukla, MD, radiation oncologist, MCW faculty member and local principal investigator of the trial. “Radiation inflames mucous membranes that have a lot of nerve endings and leads to oral mucositis. It is often painful.” 

The standard of care is to prescribe opioids to reduce the pain, often in combination with numbing medications. Opioids can produce their own side effects. Patients may feel “loopy” or out of it, experience dry mouth, constipation, nausea or upset stomach, or have difficulty withdrawing from the medication. 

Despite the drawbacks of opioids, untreated pain can compromise overall health. 

“Treatment-related pain prevents people from eating enough to meet their nutrition needs or eating at all,” Dr. Shukla said.

“Patients often lose significant amounts of weight, which can lead to weakness and fatigue. If patients don’t eat for extended periods of time, their swallowing muscles can become sluggish and stiff. A feeding tube might be needed to help sustain their nutritional needs. If we can keep people eating and drinking by mouth, they’re much better off from a functional and nutritional standpoint. Their long-term quality of life is better.” 

The phase III clinical trial will test high-dose gabapentin. It builds on preliminary research that showed that gabapentin controlled head and neck pain well, with few side effects, and reduced the need for narcotics. Gabapentin is readily available, affordable and often prescribed in generic form. 

Patients enrolled in the study must be receiving chemoradiation — radiation therapy and cisplatin-based chemotherapy, which together achieve good-to-excellent “cure rates,” according to Dr. Shukla. They will be randomly assigned to a group that receives gabapentin or a placebo. “This is a prophylactic approach, meaning preventive,” Dr. Shukla said. “Patients don’t have pain at the outset of treatment, they develop it over the course of treatment, and it becomes progressively more severe. The HOPE protocol starts at the beginning of chemoradiation with the intent to prevent and/or reduce the pain patients might experience.” 

The duration of the study is 10 weeks: a start-up period when the dosage of gabapentin is slowly increased, several weeks at the full dose, and a period when the gabapentin is tapered down. 

Study participants, whether randomized to the gabapentin or the placebo group, will still receive usual care, including opioids as needed and an array of prescription and over-the-counter remedies for soothing irritated mucous membranes. They also have access to a multidisciplinary team of head and neck cancer experts, including medical and radiation oncologists, head and neck surgeons, specialists in speech/swallowing therapy, nutritionists, physical and occupational therapists and audiologists. 

“The study aims to show that patients randomized to the gabapentin group start opioids later into their treatment course and need lower doses overall,” Dr. Shukla said. “Gabapentin has far less issues with dependency. 

“People experience pain very differently. Major concerns arise when pain is not managed adequately, namely nutritional deficiencies, rapid weight loss, weakness, hospitalization, depression and abandoning treatment altogether. Treating pain is the humane thing to do, and we have to think of people not only going through radiation therapy for head and neck cancer, but also recovering and getting them back to their pre-cancer baseline. This study is promising.”