Headache is a frequent complaint of patients with head and neck cancer. 1 The cancer pain guidelines recommended by the World Health Organization (WHO) are effective in 70% to 90% of patients with cancer pain. 2 Additional measures, including neurolytic procedures, are necessary for the remaining patients. Sumatriptan is a selective serotonin type-1D receptor agonist that binds to receptors present in cranial arteries causing vasoconstriction. 3 We report two patients with head and neck cancer and throbbing headache, refractory to opioids and steroids, who achieved relief with sumatriptan.
The use of sumatriptan for the treatment of migraine and cluster headache is well established. Sumatriptan has also been reported to be effective for the treatment of postdural puncture headache, postictal headache, and headache related to intravenous immunoglobulin infusion. We report two patients with headache caused by locally invasive head and neck cancer relieved by oral sumatriptan.
A 43-year-old man with squamous cell cancer of the larynx, treated with surgery and radiation therapy, was admitted to the hospital with worsening pain caused by progression of his cancer. He described two types of pain, a dull continuous ache on the left side of the neck and a bilateral, frontal, throbbing headache. Both pains were continuous, and there were no triggering, relieving, or worsening factors. The intensity of the neck pain and the intensity of the headache were both rated by the patient as 8 on an 11-point (0 to 10) verbal analog numeric scale (NS). The patient did not have a history of headaches prior to the cancer diagnosis and did not have a family history of headaches.
His physical examination was remarkable for aphonia, right Horner syndrome, a hard mass in the inframandibular and supramandibular regions on the right side, a right-sided neck fistula oozing small amounts of bloody fluid, tracheostomy, and gastrostomy tube. A computed tomography (CT) scan of the neck with intravenous (IV) contrast showed the tumor mass encircling and invading the carotid artery at the level of the bifurcation on the right (Figure 1).
While in the hospital, the patient was treated with an IV morphine infusion, which was gradually increased to 50 mg per hour, with significant improvement in the neck pain, rated as 5 on the NS, but no improvement in the pulsatile frontal headache. Sedation limited further increases in the morphine dose. A trial of dexamethasone (6 mg IV every 6 hours) failed to relieve the headache. A course of antibiotic treatment did not help. Ketoralac, 30 mg IV, relieved the headache but caused a substantial increase in the amount of blood oozing from the patient's neck fistula. Trilisate, 1500 mg orally, three times a day did not provide relief. A trial of 50 mg of oral sumatriptan resulted in resolution of the pulsatile headache within an hour and the effect lasted 3 to 4 hours. The patient continued to use sumatriptan on a regular basis every 3 to 4 hours, with consistent relief of his pulsatile headache after each dose until death 7 weeks later. Four weeks before death, his opioid was switched to methadone via gastric tube (250 mg every 4 hours) with improvement in the neck pain (rated 3 on a NS).
The second patient was a 71-year-old man with recurrent nasopharyngeal carcinoma invading the left base of the skull at the level of the carotid canal (Figure 2). The cancer progressed despite treatment with radiation therapy and chemotherapy. He described two distinct types of pain. The first was an intermittent “electrical” painful sensation over his left mandible that responded well to carbamazepine, 200 mg, three times a day. The second type of pain was a left temporal headache radiating from the left neck. The patient described the pain as dull, continuous, and throbbing. Photophobia, phonophobia, and nausea were not present, and there was no family history of migraine.
His physical examination was remarkable for left-sided fifth and sixth cranial nerve deficits, in addition to soft tissue swelling in the neck and left face.
The patient was treated with IV hydromorphone titrated up 5 mg per hour and IV dexamethasone with some improvement in the pain, although he still rated its intensity as moderate. He was given 50 mg of oral sumatriptan with considerable headache relief (pain rated as mild) for 2 hours. The next day the patient received two doses of oral sumatriptan (50 mg each) at 2-hour intervals with similar improvement. On the third day, the pain had changed location and character and was now described by the patient as a constant, severe ache in the occipital region, without a throbbing component. A 50-mg dose of sumatriptan was ineffective for this new type of pain. No further doses of sumatriptan were given, and the patient's pain remained severe despite rotation to different opioids including methadone, a trial of IV ketamine, and stereotactic radiation of the base of the skull.
Pain is experienced by 40% to 80% of patients with head and neck cancer, and head pain is the most frequent complaint, affecting over 80% of these patients. 1 The incidence and severity of cancer pain increase with disease progression. Tumors in the head and neck are located in close proximity to many pain-sensitive structures, such as mucosa, bones, cranial nerves, and large blood vessels. Neural spread of cancer was diagnosed pathologically in 44% of a series of patients. 4 Neuropathic pain was present in 25% of the patients described by Grond et al 1 and was present in one of our two patients.
Sumatriptan is a selective serotonin type-1D receptor agonist with well-established efficacy in the treatment of migraine and cluster headache. 5 It binds to vascular receptors on cranial arteries and produces vasoconstriction. 3 There is anedoctal evidence it might help in other types of headache such as postdural puncture headache, 6 headache related to IV immunoglobulin infusion, 7 and postictal headache. 8
Neither of our two patients had a past history or family history of migraine, had undergone a dural puncture, had received immunoglobulin therapy, or had seizures. Both had continuous throbbing headache for days, unrelieved by large doses of opioids. Corticosteroids did not substantially improve the headache in either patient. Ketoralac relieved the headache in our first patient but was associated with bleeding from his neck fistula. Patients with head and neck cancer often have ulcerating lesions in highly vascular areas, and treatment with nonselective cyclooxygenase inhibitors can increase the risk of bleeding. Both patients described the headache as throbbing, a descriptor that suggests a possible vascular contributor to the pathophysiology of the headache. Injury to the internal carotid artery, as seen in patients with carotid artery dissection, has been associated with continuous, throbbing pain located in the frontal, temporal, and orbital regions. 9 Both of our patients had tumor encircling the internal carotid artery (Figures 1 and 2). The headache was frontal in our first patient and temporal in the second patient. In both patients, the headache relief was short-lived but reproducible after each sumatriptan dose. In our first patient, the relief was maintained for several weeks on a four-times-a-day schedule. A long-acting triptan (eg, naratriptan) might have avoided repeated dosing throughout the day. Our second patient, after obtaining relief with the first three doses of sumatriptan, developed an occipital headache without a throbbing component. This new pain was most likely caused by progressive base of the skull tumor invasion. We cannot explain the permanent resolution of the throbbing temporal headache in our second patient after three doses of sumatriptan. The new, severe, occipital pain from progression of cancer may have masked the less severe pulsatile headache.
The pharmacologic approach recommended by the WHO for the treatment of cancer pain 2 should continue to guide the analgesic treatment in patients with pain secondary to head and neck cancer. Sumatriptan might be useful in selected patients when the headache is described as pulsatile or throbbing and there is radiological evidence of carotid artery involvement.