Introduction

The use of neuraxial infusion for cancer pain
first requires appropriate education for the oncologist. Many
oncologists are not familiar with intraspinal analgesia and may not
be able to contribute to clinical decisions involved in patient
selection and timing of therapy. There are no strict indications or
guidelines for this technique, and each physician must develop his or
her own approach based on knowledge of the therapy and clinical
judgment. Physicians who treat cancer patients must understand
ongoing patient management after a permanent system is implanted.
Oncologists may believe that once a device is implanted, the work is
done. Implantable infusion therapy, however—much like medical
management—involves multiple medications, multiple dose
titrations, and constant monitoring to establish a favorable
analgesia-to-side-effect profile.

Barriers to Pain Relief

The acceptance of intraspinal therapy has been impeded by numerous
barriers. These include:

• Lack of knowledge of the therapy.[1]
• Lack of double-blinded, randomized, controlled trials
  demonstrating the efficacy of this therapy and its superiority over
  conventional therapies; the current efficacy data are limited to
  prospective and retrospective surveys.
• Financial barriers
• Fear of invasiveness
• Barriers to providing pain relief in general.

Eight million people in the United States have cancer,[2] and 50%
have pain, as estimated by the World Health Organization. Therefore,
4 million patients have cancer pain.[3] With optimal medical
management, 75% to 90% of these patients attain pain relief. Four
hundred thousand cancer patients in the United States have cancer
pain each year that cannot be controlled with routine systemic
therapy under the best of circumstances. True outcomes are actually
much worse because of undertreatment.[4,5]

Medical therapies remain the mainstay of chronic cancer pain
management. The World Health Organization Ladder for Chronic Cancer
Pain Management (Figure 1) is a
valuable tool, but was intended for both developing and developed
countries and may not be sufficient for developed countries.[6]
Between 75% and 90% of patients can have their pain controlled by
following this ladder. It also provides a framework for managing
patients with intractable pain. But the ladder offers no guidance for
the management of side effects or the selection of patients for
interventional therapies.

There are different approaches to managing the patient with pain that
is poorly responsive to opioids. Oncologists are particularly good at
managing side effects and know when palliative chemotherapy and
palliative radiotherapy are indicated. They are not as familiar with
neurolytic blocks, intraspinal infusion therapies, and neurosurgical
options. In contrast, pain management physicians are more familiar
with neurolytic blocks, infusion therapies, opioid rotation, and the
use of coanalgesics. Clinicians must eliminate barriers between
disciplines (Figure 2). The
oncologist should understand when neurolytic blocks and infusion
therapies are indicated and the pain physician must understand the
full spectrum of palliative care with medical therapies, as well as
when chemotherapy and radiation therapy are needed.

Role of Intraspinal Therapy

Although medical therapies remain the mainstay of pain control, side
effects may limit the benefits of therapy. Side effects include
sedation, mental cloudiness, and constipation.[7] It is at these
times that we need to consider and position neuraxial infusion
therapies in the spectrum of options.

Both the Agency for Health Care Policy and Research and the National
Comprehensive Cancer Network have guidelines for interventional
therapies such as neurolytic blocks and infusion therapies.[8] If
these guidelines were followed, the number of patients who are
treated with neurolytic blocks or infusion therapies would probably
increase substantially.[9-11] There are also many more options for
intraspinal treatment. With intrathecal clonidine, local anesthetics,
and hydrophilic and lipophilic opioids, and even new drugs like
intrathecal ziconitide, the role of interventional neuraxial
infusions should be increasing.

It is possible that a more thoughtful approach to the use of invasive
therapies might be based on assessment of the disease process and
likelihood of responding to medical and interventional therapies. For
example, a patient with pancreatic cancer may respond to a celiac
plexus block early in the disease; this procedure has been shown to
improve pain relief, mood, and, possibly, life expectancy.[12,13] If
a patient with cancer has a new onset of back pain, the epidural
metastasis must be considered, and radiation therapy may be
recommended early. Likewise, there might be times when clinicians can
predict that a patient would do poorly with systemic opioids, and
could then intervene with intrathecal infusion approaches early to
gain as much benefit as possible. More research is needed to explore
this potential.

It is important for pain management specialists to discuss with
colleagues in oncology the potential advantages of epidural and
intrathecal infusions. Epidural and intrathecal infusions:

• Can be effective for multiple pains
• Are titratable
• Are nondestructive and safe
• Require low doses of opioids, and can have a lower side-effect
  liability than the systemic opioids
• Offer the possibility of adding intraspinal coanalgesics
• Can be cost-effective.[14]

Furthermore, neuraxial opioids have no motor, sensory, or sympathetic
effects. The normal conversions from systemic to intrathecal opioids
range anywhere from 200:1 to 600:1. The oral/epidural conversion for
morphine is 30:1, and for oral/intrathecal conversion, 300:1. The
lower dose needed to produce effects may lead to a better side-effect
profile in most patients.[15]

Intrathecal Infusion Studies

The theoretical advantages of intraspinal therapy are complemented by
several retrospective studies and case reports that intrathecal
morphine is effective in the treatment of cancer pain.[15-18]
Although most surveys of intraspinal therapy revealed high success
rates, many patients entered into these surveys were not required to
develop side effects prior to proceeding to an implanted device. It
also is not clear how much work was done to control side effects
before the patient received the implanted device, or whether opioid
rotation was tried. For this reason, spinal therapy is usually still
considered an approach for managing patients with pain that is
refractory to an optimally administered systemic opioid regimen.

Need to Increase Awareness

Recently, a study assessing attitudes of oncologists toward
interventional cancer pain management was conducted.[1] A series of
qualitative (74) and quantitative (230) interviews were carried out
in a sample group of 304 cancer health care specialists. Qualitative
tests included focus group discussions and quantitative evaluations
included computer-aided telephone interviews.

Pain assessment techniques used by cancer care personnel had little
emphasis on the more accurate multidimensional assessment techniques.
Extended release morphine sulfate preparations were found to be the
most commonly prescribed analgesic in this project with lower doses
(0 to 300 mg/day) considered to be within their margins of comfort by
73% of those studied. A total of 81% of oncologists reported patient
referral to pain specialists to be a part of their current practice (Figure
3). The familiarity with intrathecal therapy was low, with only
46% having referred patients for intrathecal therapy in the previous
12 months. The invasive nature of device placement was deemed a
drawback by 42% of physicians. The study indicates that continued
education of both patient and physician is essential to ensure that
all means of treatment are available to cancer pain patients.