Epidural Morphine Relieves Pain in Advanced Cancer, But May Not Influence Quality of Life

OXFORD, UK-Epidural delivery of opioids effectively relieves painin patients with advanced cancer who are intolerant of or insensitiveto high-dose oral morphine, but improvement in quality of lifemay be more difficult to achieve, Christopher Glynn, MB, saidat a workshop on pain management in palliative care, held at theVancouver meeting.

For patients with a terminal disease, quality of life might betterbe termed quality of dying, he said, and for these patients, accordingto his study results, pain relief alone may not lead to reportedimprovements in quality of life.

"This finding came as quite a shock," Dr. Glynn said."We thought that having relieved the pain in these patients,we would have an effect on their quality of life."

Dr. Glynn and his colleagues in the Pain Relief Unit, ChurchillHospital, Oxford, audited the records of 52 cancer patients whohad received epidural morphine at home. "All but one diedat home with continuous epidural systems in place," he said.

The researchers found few complications with the system. Amongall cancer patients sent home with an epidural (probably 50 to75 a year), "we've had only one infection," he said."Reinsertion has not been a problem. We've offered to putin an implantable system when catheters fall out, and no patienthas required this. They like the simplicity of the system, andits simplicity is its beauty."

In this series, the median starting morphine dose was 10 mg/dayand the finishing dose was 30 mg/day, with most patients requiringno more than two or three dose revisions. "Some patientsrequired as much as 200 mg/day, but by and large, daily doseswere below 100 mg," Dr. Glynn said. He added that, at thesedosages, side effects have not been a problem.

Patients also received bupivicaine at a median dose of 42 mg/day."Patients have the ability with the syringe driver to boostthe bupivicaine dose for incident, or movement-related, pain,to enable them to mobilize," he said. Clonidine was addedto the regimen for patients with neuropathic pain.

To evaluate the effects of the treatment on quality of life, theresearchers wrote to the patients' general practitioners to getpermission to approach the surviving spouse, and eventually receivedcompleted questionnaires from 22 of the spouses.

Although data from spouses may be less reliable, Dr. Glynn believesit would be difficult to do such a study prospectively in terminalpatients "in a way that is not going to upset people."

These 22 patients experienced a significant decrease in pain withepidural morphine, but most of the spouses reported that the patient'squality of life was the same or worse after the epidural. Spousesreported that the factor having the greatest negative effect onthe patient's quality of life was the diagnosis of the cancer,followed by pain and the dying itself.

"Quality of life may not work as an outcome measure for painrelief ," Dr. Glynn said. The message, then, is that in thevast majority of patients, "we can expect to relieve pain,but don't expect to improve quality of life."

Try Opioid Rotation First?

Speaking from the audience, Nathan Cherny, MD, formerly of MemorialSloan-Kettering Cancer Center and now director of the Cancer PainService at Shaare Zedek Medical Center, Jerusalem, questionedwhy other oral opioids were not tried in these patients beforeresorting to spinal morphine.

Dr. Glynn acknowledged a bias in favor of going directly fromoral morphine to intraspinal therapy. "If they haven't hada proper trial of oral morphine, they get it from us," hesaid. "But if we can't make oral morphine work, we have asystem that will work."

He noted that in 5 years, only one patient has refused epiduralanalgesia. "It is a system that works rapidly and gives goodpain relief. If you're going to work your way through the otheropioids, then time is a factor--you're talking about a 10-dayto 2-week hospital stay if you try three different drugs. We electto avoid that time factor."

Dr. Cherny pointed to a prospective survey of 100 consecutivepatients referred to the Memorial Sloan-Kettering Pain Service.About half of this series (52 patients) received additional trialsof one or more oral opioids. These were patients who had uncontrolledpain with morphine despite dose-limiting side effects or painthat was controlled only at doses producing unacceptable toxicity.

Twenty of these patients received sequential trials of three ormore agents before discharge home (18 patients) or death (2 patients).In this same series, 12 patients had a trial of spinal opioids,and 6 were discharged using this approach. The only indicationfor spinal routes cited by the involved clinicians was persistentdose-limiting toxicities with systemic opioids.

"We found that the median time needed for a trial of an opioidwas between 2 and 3 days, or only about 7 days to try three drugs.So we knew where we stood fairly quickly before making a decisionto go to the spinal route."

Dr. Cherny noted that the 30 patients in whom only one alternativeopioid was tried may have unnecessarily gone on to more invasivemethods, when a trial of an additional one or two drugs mighthave led to adequate systemic pain relief.

Dr. Glynn countered that most of his patients who receive epiduralsare morphine insensitive, "and if they are morphine insensitive,I don't think there's any evidence that any other opioids willwork. In morphine-sensitive patients with intolerable side effects,then a trial of another agent might be appropriate."

A physician from the University of Utah mentioned that the FederalAHCPR guidelines on cancer pain, using an evidence-based approach,found that less than 5% of all cancer pain patients were appropriatecandidates for epidural or intrathecal opioids, and that, in hisopinion, tertiary centers tend to overuse the spinal route.

In an interview, Dr. Cherny said that in the near future, slow-releaseforms of hydromorphone and oxyco-done should be available in theUnited States, making trials of morphine alternatives even morefeasible.