Nontraditional Analgesics Have a Role in Fighting Cancer Pain

COLUMBUS, Ohio--Recent clinical reports of nontraditional analgesics, like calcitonin, gabapentin (Neurontin), and tramadol (Ultram), suggest that these drugs may successfully control cancer pain in some patients, said Mary Beth Shirk, PharmD, clinical assistant professor, College of Pharmacy, Ohio State University. In some patients, the drugs have been shown to be effective against neuropathic pain.

Although the analgesic pharmacology of these agents is still under investigation, history has shown that drugs are often identified as painkillers long before their mechanism of action is fully understood. Dr. Shirk described the findings of nearly 20 recent clinical reports conducted worldwide at a conference on narcotics and pain management sponsored by Ohio State University .

Tramadol. A double-blind, placebo-controlled study of 23 patients with diabetic neuropathy suggests that tramadol, known to be effective against postoperative and acute pain, may also be effective against neuropathic pain (Erdine: 8th World Congress on Pain, 1996). However, its potential side effects are serious, Dr. Shirk said. Nausea is common, as is dizziness. "It’s important to start with low doses and titrate up slowly," she told Oncology News International. In the study reported by Erdine, patients received 100 mg of tramadol every 12 hours.

Gabapentin. This agent, approved in 1994 as an adjunctive agent for seizure control, has been shown to be effective for neuropathic pain, Dr. Shirk said. A study of 82 patients with chronic pain showed a "favorable response" with gabapentin (Frinkel: American Pain Society Annual Meeting, 1995).

Side effects, which may include somnolence and dizziness, are minor. Blood monitoring with gabapentin is unnecessary. The dose must be adjusted for renal dysfunction, however, Dr. Shirk said. She also pointed out that gabapentin is a very expensive medication.

Calcitonin. Salmon calcitonin has been studied for its analgesic properties since the 1970s. The data suggest it is effective as an analgesic for bone pain. "It may prevent the development of problems for patients at high-risk for bone metastasis," Dr. Shirk said. She anticipates continued research in this area.

Another promising area for calcitonin is its use with phantom limb pain. In one cross-over study, 21 patients were given an infusion of salmon calcitonin. One week after treatment, 19 patients reported pain relief of more than 50%, and 76% were pain free (Jaeger H, Maier C: Pain 48:21-27, 1992).

Dextromethorphan. NMDA receptor antagonists, like dextromethorphan, are new in pain management and have shown promise. "This is an exciting area," Dr. Shirk said. Animal studies suggest that dextromethorphan can prevent opioid tolerance and can even reverse opioid tolerance once it develops.

Small studies have been conducted examining the use of dextromethorphan to treat neuropathic pain. Although one such study found no significant difference between dextromethorphan and placebo, Dr. Shirk described the study design as "questionable" (McQuay HJ et al: Pain 59:127-133, 1994). Another study reported blurred vision, sedation, and dizziness as side effects associated with dextromethorphan (Park: Annual Meeting of the American Pain Society, 1995).

Ketamine. There has been an increase in interest in ketamine (Ketalar), an anesthetic drug, in the past few years, Dr. Shirk said. Ketamine, an NMDA receptor antagonist, has been studied in cancer pain, neuropathic pain, phantom limb pain, postoperative pain, and post-herpetic neuralgia. In a study of 18 patients with cancer pain, ketamine was effective in 13 patients (Oshima E et al: Canad J Anaesth 37:385-386, 1990). "We find it very effective for resistant patients who are on high-dose opioids," Dr. Shirk told Oncology News International.

The side effects of ketamine include hallucinations and out-of-body experiences. Although ketamine is not a controlled substance, "it should be," she said. It is very similar to the street drug known as "angel dust" and is sold on the street as "Special K."

Capsaicin. Capsaicin (Zostrix), an over-the-counter cream derived from hot chili peppers, has been studied for use in neuropathic pain. In one study, 13 of 19 patients with postmastectomy pain syndrome reported a reduction in pain with use of topical capsaicin. Two patients reported a complete disappearance of all symptoms (Dini D et al: Pain 54:223-226, 1993).

"The potential toxicities of this product are tremendous," Dr. Shirk said, and may include burning, stinging, erythema, cough, and respiratory irritation. Patients need to be taught how to use this product, including avoiding contact with the eyes and using caution when handling contact lens after application.

Paroxetine. The antidepressant paroxetine (Paxil), a selective serotonin reuptake inhibitor, has been studied for its effectiveness in diabetic neuropathy. Nineteen patients completed a study comparing paroxetine with imipramine. The researchers concluded that paroxe-tine significantly reduced the symptoms of peripheral diabetic neuropathy (Sindrup SH et al: Pain 42:135-144, 1990).

These adjuvant drugs show individual variation from patient to patient, Dr. Shirk said, and it is very important to monitor their effectiveness, especially since they are quite expensive. "It’s really important to evaluate the drug’s efficacy and to discontinue the agent if it’s not improving quality of life for your patient," she said.