1. The Facts About Effectively Managing Intractable Cancer Pain
© Medtronic, Inc. 2009

2. Sources of Pain in Cancer Patients
Cancer pain comprises:
Acute pain
Chronic pain
Tumor-specific pain
Treatment-related pain
Carr D, Goudas L, Lawrence D, et al. Management of cancer symptoms: pain, depression, and fatigue. Evidence report/technology assessment No. 61 (prepared by the New England Medical Center Evidence based Practice Center under contract No ). AHRQ Publication No. 02-E032. Rockville, MD: Agency for Healthcare Research and Quality. July Downloaded at
on 4/22/ Accessed 03/23/2009

3. Existence of pain due to cancer
More than two thirds of cancer patients report pain which they attribute to their cancer
From S5 - Patients currently suffering from pain
More than 50% of patients with the following types of cancer currently suffer from pain:
Lung
Pancreatic
Brain Tumour
Bone/Muscle
Blood Borne
Non-Hodgkins
Head/Neck
Leukaemia
Base: all screened – (individual base sizes shown on chart)
S4. Have you suffered any pain due to your cancer?
European Pain in Cancer (EPIC) Global Results Presentation, July 2007

4. Where We Are Today in Managing Cancer Pain?
Minorities, women, and the elderly are particularly at risk for cancer-related pain.1
One survey found that while health care providers believe they are doing a good job at managing pain and its symptoms, families do not.2
Cancer pain still pervasive in adults and children.3
Cancer pain is undertreated in all settings where patients with cancer are managed.3
1. Carr D, Goudas L, Lawrence D, et al. Management of cancer symptoms: pain, depression, and fatigue. Evidence report/technology assessment No. 61 (prepared by the New England Medical Center Evidence based Practice Center under contract No ). AHRQ Publication No. 02-E032. Rockville, MD:Agency for Healthcare Research and Quality. July Downloaded at on 4/22/ Accessed 03/23/2009
2. Tolle SW. Family reports of pain in dying hospitalized patients: a structured telephone survey. West J Med. 2000;172:
3. Guideline for the Management of Cancer Pain in Adults and Children p x.

5. You Are The Patient’s Advocate
Patients with cancer are often reluctant to report the extent of their pain1
Fear that reporting pain will take physician time away from their treatment
Concern about addiction
Beliefs that “good” patients do not complain about pain
Concern about side effects with escalating doses
Result = under-treatment of pain
1. Ward S, Goldberg N, Miller-McCauley V, et al. Patient-related barriers to management of cancer pain. Pain. 1993;52:

6. The Effects of Pain
A majority of patients experience pain at some point during their course of cancer treatment.1
Cancer pain impairs quality of life and functionality.1
The cost of inadequate pain control and related side effects (of pain medications) is high, both in terms of impaired function and quality of life.2-4
Pain interferes with all activities of daily living.5
1. Carr D, Goudas L, Lawrence D, et al. Management of cancer symptoms: pain, depression, and fatigue. Evidence report/technology assessment No. 61 (prepared by the New England Medical Center Evidence based Practice Center under contract No ). AHRQ Publication No. 02-E032. Rockville, MD:
Agency for Healthcare Research and Quality. July Downloaded at on 4/22/ Accessed 03/23/2009
2. Smith TJ, Staats PS, Deer T, Stearns LJ, et al. Randomized clinical trial of an implantable drug delivery system compared with comprehensive medical management for refractory cancer pain: Impact on pain, drug-related toxicity, and survival. J Clin Oncol. 2002;20(19):
3. Cleeland, CS. Undertreatment of cancer pain in elderly patients. JAMA 1998;279(23):
4. Stearns L, Boortz-Marx R, Du Pen S, Friehs G, et al. Intrathecal drug delivery for the management of cancer pain: a multidisciplinary consensus of best clinical practices. J Support Oncol. 2005;3(6):
5. Mystakidou K, Tsilika E, Parpa E, et al.: Psychological distress of patients with advanced cancer: influence and contribution of pain severity and pain interference. Cancer Nurs 29 (5): 400-5, 2006 Sep-Oct.

7. Pain as the “Fifth Vital Sign”
The Joint Commission on Accreditation of Healthcare Organizations (JCAHO) issued a comprehensive description of patients’ rights and standards of care for pain management.
Recommendation: make pain assessment/management priority in daily practice
Consider pain intensity the 5th vital sign: measure along with temperature, pulse, respiration, and blood pressure
Patients’ rights: full pain workup when pain is not easily characterized or treated
JCAHO,

8. Start with a Comprehensive Pain Assessment
The National Cancer Institute recommends that the clinician help the patient describe pain1:
Location
Changes in pattern
Intensity or severity
Aggravating and relieving factors
Cognitive response to pain
Goals for pain control
These are essential to the initial assessment:1
Detailed history1
Physical examination1
Psychosocial assessment2
Diagnostic evaluation1
An accurate pain assessment helps to select an appropriate treatment for the patient’s pain level.
Traditionally, the Visual Analog Scale (VAS) has measured intractable pain. Today, pain management specialists incorporate additional methods of analysis. The National Cancer Institute recommends that to enhance pain management, clinicians teach families to use pain assessment tools in their homes. The clinician should help the patient describe pain using the steps outlined above.
1. National Cancer Institute Accessed May 12, 2009
2. Otis-Green S, Sherman R, Perez M, et al.: An integrated psychosocial-spiritual model for cancer pain management. Cancer Pract 10(Suppl 1): S58-65, 2002 May-Jun. 

9. Characterize the pathophysiology of pain Determine intensity of pain
Assessment Goals
Characterize the pathophysiology of pain
Determine intensity of pain
Determine impact on patient’s ability to function
1. National Cancer Institute Accessed May 12, 2009

10. Cancer Pain Therapy: The Oncologist’s Perspective
Systemic pharmacologic therapy
Collaboration with pain medicine and palliative care specialists
Good pain management facilitates good cancer management
Systemic pharmacologic therapy is the mainstay of cancer pain management, but oncologists need to explore other options for patients with intractable pain.
Despite the appropriate use of pharmacologic guidelines, there will be a subset of patients whose comfort and function is unacceptable. For these patients, oncologists should consult and collaborate with a pain or palliative care specialist.
Good pain management facilitates good cancer management. If patients are in too much pain, it can cause difficulty in lying on the radiation table or even in getting to chemotherapy appointments. In addition, there are a significant number of cancer survivors who have chronic treatment-related pain.
Levy MH. Pain control in patients with cancer. Oncology. 1999;13(5 suppl 2):9-14.
Levy MH. Pain control in patients with cancer. Oncology. 1999;13(5 suppl 2):9-14.

11. Multidisciplinary Approach to Chronic Pain Management
Multidisciplinary Solution
Physiological
factors
Social
Psychological
Complex Problem
Pain specialists
Psychologists
Nurses
Social workers
Rehabilitation
specialists
Multidisciplinary Approach to Pain Management
Chronic pain is a complex phenomenon and is best managed by a
multidisciplinary team.
Primary coordination of treatment may depend on the individual patient’s
needs and may change over time.
For example, at one point the pain specialist’s input may be most urgent;
subsequently, the rehabilitation specialist’s efforts may be most
important, while at another point psychological therapy may be
what the patient needs most.
Pain management challenges these disciplines to work together, often
for long periods of time.

12. Cancer Pain Management Strategies
Pharmacologic strategies
Nonopioid analgesics
Acetaminophen
Nonsteroidal anti-inflammatory drugs
Opioid analgesics
Coanalgesics (adjuvant analgesics)
Physical strategies
Massage
Exercise
Transcutaneous electrical nerve stimulation (TENS)
Acupuncture
Psychological strategies
Hypnosis or relaxation with imagery
Cognitive-behavioral methods
Nerve blocks
Radiation therapy
Chemotherapy
1. Guideline for the Management of Cancer Pain in Adults and Children p

13. Opioid Analgesics for the Treatment of Cancer Pain
Used most often in the management of severe pain because:1
Effectiveness
Ease of titration
Favorable risk-to-benefit ratio
Routes of administration2
Oral
Transdermal
Parenteral: Intravenous or subcutaneous
Intraspinal: Epidural or intrathecal
Consider when other routes of administration cannot control pain or when side effects limit further dose escalation
Guideline for the Management of Cancer Pain in Adults and Children p 53
Ibid., p 64.

14. Advanced Strategies for Intractable Cancer Pain Management
10-20% Invasive Therapy Needed
Patients receiving oral/transdermal opioids and adjuvant therapy may experience adequate pain control in 80-90% of the cases.
Thus in 10-20% of the patients, some form of invasive therapy will be needed to control refractory pain, despite aggressive titration.
Invasive therapy may include:
Nerve blocks
Epidural analgesia
Intrathecal analgesia
80-90% Adequate Pain Control
Jacox A, et al. AHCPR, 1994.
Portenoy R. Oncology 1999;S2:7.

15. Spinal Anatomy Intrathecal Space (Subarachnoid Space) Epidural Space
Arachnoid Membrane
Dura
Pia Mater
Spinal Cord
Nerve Root
To understand the physiology of intraspinal opioids, it is helpful to review spinal anatomy.
The spinal cord is surrounded by three meningeal layers:
The outermost layer is the dura mater, or dura, which is a thick, dense membrane that protects the brain and spinal cord.
An epidural space separates the dura and the vertebrae. The epidural space is composed of fatty tissue and can be used as a site for drug delivery with opioid therapy.
The dura is adhered to the next meningeal layer, the arachnoid membrane.
The arachnoid membrane is separated from the pia mater by a large subarachnoid, or intrathecal, space filled with cerebrospinal fluid. This clear, colorless fluid bathes the spinal cord and the brain, cushioning them from impact. The intrathecal space can also be used in intraspinal drug delivery.
The third meningeal layer of the spine is the pia mater which covers the spinal cord.

16. Epidural vs. Intrathecal Space
(Subarachnoid
Space)
Epidural
Space
Keep in mind that the term “intraspinal administration” can refer to the delivery of analgesia to either the intrathecal or epidural space.
It is extremely important to be able to differentiate the epidural and intrathecal spaces for intraspinal analgesia because:
Some systems are designed for use in only the epidural space.
The potency of an analgesic varies greatly when dosing for intrathecal versus epidural delivery. For example, a dose of preservative-free intrathecal morphine is approximately one-tenth of an equianalgesic epidural dose.
The rate of drug absorption differs with epidural and intrathecal delivery.
There are pros and cons to each delivery route, which we will overview in a moment.

17. Physiology of Spinal Opioids
Nociceptors carry a “pain” signal to the dorsal horn.
In the dorsal horn neurons release substance P.
Substance P triggers ascending neurons that carry this signal to the brain.
Opioids inhibit the release of substance P, blocking the pain transmission.
Perceived pain is reduced.
Pain Signal Initiated
Pain Perceived
The physiology of pain begins with sensory neurons called nociceptors. A pain message is transmitted along these neurons to the dorsal horn of the spinal cord. 1
In the dorsal horn, sensory neurons release several neurotransmitters that act on the dendrites of ascending neurons. Eventually, these ascending neurons carry the signal to the brain where it is perceived as pain. 1
One of the key neurotransmitters in pain transmission is substance P. Opioids inhibit the release of substance P by bonding to sensory neurons. This, in effect, blocks the message before it reaches the brain and is perceived as pain. 1
1 Gianino, J., York, M., Paice, J. Intrathecal Drug Therapy for Spasticity and Pain. New York, NY: Springer-Verlag; 1996.

18. Epidural vs. Intrathecal Opioids
Some physicians prefer epidural delivery because there is a lower risk of respiratory depression than with intrathecal delivery.1
There may also be a lower risk of serious complications because the dura is not punctured with epidural catheter placement.
However, if analgesic is delivered epidurally, 80 to 90% of the drug is absorbed systemically. Therefore, more drug reaches the systemic circulation, which may lead to a greater incidence of side effects such as constipation and urinary retention.1
In addition, epidural catheter placement has been associated with dural scarring, which inhibits opioid effectiveness.
Intrathecal
Some clinicians feel that intrathecal delivery is the preferred route for intraspinal drug delivery. 1
Intrathecal administration has the advantage of lower drug dose and faster onset of analgesia. With intrathecal delivery there is also the option of CSF sampling for culture, diagnosis, and drug levels. 1
Opioids delivered directly to the intrathecal space are particularly effective because they do not have to circulate systemically to reach the CSF and the dorsal horn of the spinal cord. 2 As a result, patients treated with this therapy generally experience fewer side effects than with epidural administration. 1
The disadvantages of intrathecal delivery include the risk of CSF leakage (leading to spinal headaches), respiratory depression and an increased risk of meningeal infection. 1
1 Levy, R. Implanted Drug Delivery Systems for Control of Chronic Pain. Chapter 19 of Neurosurgical Management of Pain. New York, NY: Springer-Verlag; 1997.
2 Gianino, J., York, M., Paice, J. Intrathecal Drug Therapy for Spasticity and Pain. New York, NY: Springer-Verlag; 1996.
1. Levy, R. Implanted drug delivery systems for control of chronic pain. Chapter 19 of Neurosurgical Management of Pain. New York, NY: Springer-Verlag;1997.

19. What is successful pain management?
Success = Pain relief – Unmanageable side effects

20. Side Effects of Cancer Pain Medications
Fatigue: more prevalent than pain in patients with metastatic cancer
Depressed level of consciousness, sedation: dose-limiting problems, may be treated with methylphenidate (Ritalin*)
Constipation: managed with laxatives
Nausea: managed with antiemetics
Delirium, confusion: relatively rare
Respiratory depression: very unusual
Fatigue is more prevalent than pain in patients with metastatic cancer. Pain, anxiety, depression, and insomnia all contribute to fatigue, as do drug side effects, infection, and neurologic problems.
Depressed level of consciousness and sedation are serious dose-limiting side effect of opioids.  However, these symptoms can be treated with methylphenidate (Ritalin).
Constipation is the most frequent side effect of opioid therapy but one that is usually treated prophylactically. Because opioids permanently slow gut motility, laxatives should be prescribed for any patient taking opioids. In general, the higher the opioid dose, the more laxative/stool softener is necessary.  
The incidence of opioid induced nausea has been estimated to be 10%-40% and tolerance usually develops rapidly,typically 3-5 days or less.
Cherny, N., Foley, K. Nonopioid and Opioid Analgesic Pharmacotherapy of Cancer Pain. In Hematology/Oncology Clinics of North America Vol.10. NO1, 2/96 PP
Antiemetics should be available prophylactically if needed.
Delirium and confusion are rarely caused by opioids alone. Contributing factors include brain lesions, oxygen depravation, metabolic or electrolyte imbalances, infections, or drug interactions. Sometimes delirium resolves if the opioid medication or dose is changed.
Respiratory depression is rare.
Abrahm JL. A Physician’s Guide to Pain and Symptom Management in Cancer Patients. Baltimore, Md: The Johns Hopkins University Press; 2000.
Abrahm JL. A Physician’s Guide to Pain and Symptom Management in Cancer Patients
*Ritalin is a registered trademark of Novartis Pharmaceuticals Corporation.

21. Route of Administration Relative Potency (mg)*
Approximate Equivalent Daily Doses of Morphine Administered by Various Routes
Route of Administration
Relative Potency (mg)*
Oral
Intravenous
Epidural
Intrathecal
300
100 20 1
*Relative approximations based on clinical observations
Lamer TJ: Mayo Clin Proc.1994 May;69(5): Review. 21

22. Reduce Dose → Reduce Side Effects
1 mg intrathecal morphine = 300 mg oral morphine
The primary advantage of intrathecal pain therapy is the dramatic reduction in the amount of medication required for pain relief.
Because medication goes directly into the spinal cord, much smaller doses are required than with oral or intravenous methods.
Typically, the intrathecal to oral dose conversion is 1:300.
Patients treated with this therapy can experience fewer side effects than with oral drug delivery.
Krames ES. J Pain Symptom Manage Jun;11(6):
Krames ES. J Pain Symptom Manage Jun;11(6):

23. Intrathecal Drug Delivery: Patient Selection Criteria
I. Symptoms of pain due to advanced stage cancer at presentation, with a minimum life expectancy of >3 months1-4
II. Refractory to conventional pain management because of drug toxicity or unsatisfactory analgesia1-4
III. Visual analog scale (VAS) of ≥ 5, despite 200 mg/day of oral morphine or the analgesic equivalent1,3,4
1. Smith TJ, Staats PS, Deer T, Stearns LJ, et al. Randomized clinical trial of an implantable drug delivery system compared with comprehensive medical management for refactory cancer pain: Impact on pain, drug-related toxicity, and survival. J Clin Oncol. 2002;20(19):
2. Stearns L, Boortz-Marx R, Du Pen S, Friehs G, et al. Intrathecal Drug Delivery for the Management of Cancer Pain: A Multidisciplinary Consensus of Best Clinical Practices. J Support Oncol. 2005;3(6):
3. Smith TJ, Coyne PJ. Implantable Drug Delivery Systems (IDDS) After Failure of Comprehensive Medical Management (CMM) Can Palliate Symptoms in the Most Refractory Cancer Pain Patients. J Pall Med. 2005;8(4):
4. Brogan, SE. Intrathecal Therapy for the Management of Cancer Pain. Curr Pain Head Rep. 2006;10:

24. Intrathecal Drug Delivery: Patient Selection Criteria continued
Consider those on lower doses if opioid side effects are refractory to conservative treatment and severe enough to prevent upward titration.1,3,4
IV. Consider early evaluation of intrathecal drug delivery for those with pelvic tumors who may have eventual nerve compression.2
1. Smith TJ, Staats PS, Deer T, Stearns LJ, et al. Randomized clinical trial of an implantable drug delivery system compared with comprehensive medical management for refactory cancer pain: Impact on pain, drug-related toxicity, and survival. J Clin Oncol. 2002;20(19):
2. Stearns L, Boortz-Marx R, Du Pen S, Friehs G, et al. Intrathecal Drug Delivery for the Management of Cancer Pain: A Multidisciplinary Consensus of Best Clinical Practices. J Support Oncol. 2005;3(6):
3. Smith TJ, Coyne PJ. Implantable Drug Delivery Systems (IDDS) After Failure of Comprehensive Medical Management (CMM) Can Palliate Symptoms in the Most Refractory Cancer Pain Patients. J Pall Med. 2005;8(4):
4. Brogan, SE. Intrathecal Therapy for the Management of Cancer Pain. Curr Pain Head Rep. 2006;10:

25. Contraindications to Intrathecal Drug Delivery
When infection is present
When pump implant depth exceeds depth specified in pump labeling
Intrathecal Drug Delivery Contraindications
When body size is not sufficient to accept pump bulk and weight
When contraindications exist relating to the drug
Drugs with preservatives
Do not use the patient control device, if applicable, to administer opioid to opioid-naïve patients or to administer ziconotide
For a complete list of contraindications, refer to the manufacturer labeling for the specific device.

26. Initiating Intrathecal Drug Delivery
Goals of care:
clearly expressed in regard to invasive therapy
Pain-related factors:
pathophysiology amenable to intrathecal therapy
Treatment-limiting side effects from systemic therapy:
somnolence or cognitive impairment
The goals of care should be clear to both patient and physician.
The pain must be potentially amenable to intrathecal therapy. The preimplantation trial allows pain relief and side effects of intrathecal therapy to be evaluated before committing to implantation.
Central nervous system toxicity–such as sedation, mental clouding, or frank confusion–more strongly suggest the utility of intrathecal drug delivery than do gastrointestinal toxicity side effects, such as nausea.
Portenoy RK. Managing pain in patients with advanced cancer: the role of neuraxial infusion. Oncology. 1999;13(5suppl 2):7-8.
Portenoy RK. Managing pain in patients with advanced cancer; the role of neuraxial infusion. Oncology. 1999;13(5 suppl 2):7-8.

27. Trial for Intrathecal Drug Delivery
To evaluate patient’s response
Assess pain relief
Evaluate side effects
50% pain reduction
considered a positive result
One of the advantages of implantable drug delivery systems is that the patient can be tested for responsiveness before a system is implanted.
When you identify an appropriate cancer patient, the patient is informed of treatment options. If the patient and clinician decide to proceed, the patient is referred to a pain specialist or other implanting physician for a trial of intrathecal therapy.
In a trial, a dose of medication is administered intrathecally or epidurally to determine if the patient may get pain relief with an implanted system.
If the patient achieves pain relief of ≥50% with tolerable side effects, the trial is considered successful and the patient and physician may decide to proceed with the implantation of a drug delivery system.
Hassenbusch SJ, Stanton-Hicks M, Covington EC. Long-term intraspinal infusions of opioids in the treatment of neuropathic pain. J Pain Symptom Manage. 1995;10(5):
Hassenbusch SJ, Stanton-Hicks M, Covington EC. Long-term intraspinal infusions of opioids in the treatment of neuropathic pain. J Pain Symptom Manage. 1995;10(5):

28. Intrathecal Drug Delivery: SynchroMed® II Infusion System
The SynchroMed® infusion system from Medtronic became commercially available for the administration of intrathecal morphine for chronic pain in More than 75,000 patients worldwide have had the SynchroMed Infusion System implanted.
It is totally implantable, offering greater convenience for the patient, assured patient compliance with dosing regimen, fewer complications compared with external systems, and maintenance of continuous drug levels.
The programmability of the SynchroMed pump allows the clinician to titrate the drug dosage and delivery time to meet the needs of the individual patient.
A programmer communicates to the pump via telemetry, allowing the clinician to alter the dose rate or amount of drug delivered non-invasively.

29. Implanted Pump and Catheter
Intraspinal Catheter
Pump
Pump placement
Left or right abdomen
Enough tissue for support
Catheter placement
Tunnel between spinal column and pump
myPTM®
Optional feature that gives patients the control and ability to respond to intermittent pain of varying intensity
Indicated only for preservative-free morphine
Intrathecal pain therapy is delivered by an implanted catheter connected to
an implanted pump that releases prescribed amounts of medication –
commonly morphine – into the spinal fluid.
Intrathecal delivery enables the medication to reach the opiate receptors in the dorsal horn of the spinal cord almost immediately.
By avoiding systemic distribution of medication, many side effects can be greatly reduced.

30. Patient Management and Refills
Refills and programming performed by trained clinician
Refill complete in minutes
Reimbursed procedure
The interval between refills varies according to the prescribed drug and dose.
Some oncologists prefer to refill the pump at their offices. Others choose to have the pain specialist perform pump refills.
Only a trained clinician (physician or nurse) may perform the refill, which typically takes 15 to 30 minutes. During a refill the clinician:
Aspirates unused drug from the SynchroMed® infusion system.
Fills the pump with the prescribed drug using a special refill kit.
Programs new prescription information using a specialized N’Vision® programmer (physician only).
Records the aspirated drug volume in patient’s records.
Compares the expected residual drug volume with actual residual drug volume.
Records the amount of new drug in the patient’s records.
Schedules the next refill.

31. Adverse Events with Intrathecal Drug Delivery Therapy
There may be complications. The most frequently reported problems following intrathecal drug delivery system implant surgery include:
Infection
Spinal fluid leak
Pump inversion
Skin erosion
Drug side effects
Loss of therapy effect
Therapy that did not meet the patient’s expectations
Some of the most severe reported problems associated with intrathecal drug delivery therapy for intractable pain include:
Inflammatory mass (a mass near the tip of the catheter)
Spinal cord damage
Meningitis
Life-threatening drug adverse effects due to over infusion as a result of programming or patient monitoring errors or device malfunction
Complications due to use of unapproved drugs or not using drugs in accordance with drug labeling

32. myPTM®* for Management of Intermittent Pain
The Medtronic myPTM® is an optional feature of the SynchroMed II infusion system that allows patients to respond to intermittent pain of varying intensity with a physician-prescribed dose of medication from the pump. It is not for use with ziconotide.
Prevalence of Intractable Pain
74% of patients
The percentage of patients with chronic non-cancer pain who experienced severe to excruciating breakthrough pain (n = 228).1
2.4 episodes/day
The mean number of breakthrough pain episodes (defined as transitory exacerbation of pain that occurs on a background of otherwise controlled pain).1
60 minutes/pain episode
Median duration of breakthrough pain episodes.1
*In some cases, myPTM is a self-pay device. Check with your patient’s insurance before prescribing.
1. Portenoy RK, Bennett DS, Rauck R, et al. Prevalence and characteristics of breakthrough pain in opioid-treated patients with chronic noncancer pain. J Pain. August 2006;7(8):

33. myPTM®* for Management of Intermittent, Variable Pain
The nature of pain is that it is variable. The occurrence and severity may change at particular times of the day, may be associated with particular activity, or may be unpredictable and have no pattern.
myPTM® is an innovative enhancement to SynchroMed® II infusion system that gives patients the control and ability to respond to symptoms of episodic pain at onset.
*In some cases, myPTM is a self-pay device. Check with your patient’s insurance before prescribing.

34. Pump used for chemotherapy since 1988
Reimbursement
Pump used for chemotherapy since 1988
FDA-approved for use with morphine in 1991
Implant, refills, and programming covered by Medicare and most private carriers (check regional carriers for coverage)
Medtronic offers assistance with coding, coverage, and payment information
Implanted pump technology has been used for chemotherapy since 1988 and was approved for use with morphine in 1991.
The implant procedure and ongoing therapy — including pump refills and programming — are covered by Medicare in all 50 states and by most private insurers.
Levels of coverage do vary, so check with carriers before implantation.
Medtronic offers assistance with coding, coverage, and payment information.
Most reimbursement issues can be resolved, so candidates for implant should not be ruled out due to economic constraints.

35. Cost Effectiveness of Intrathecal Therapy in Cancer Pain
Infusion costs are generally comparable for externalized intraspinal and parental drug delivery because similar equipment is used.1
One cost model showed the break even point at which it becomes less expensive to administer opioids with an intrathecal/implanted pump (rather than an epidural/external pump) is between three and six months after the start of pain management.2
After approximately 12 weeks, an exteriorized system loses its cost advantage, mainly due to higher maintenance needs and higher drug costs.3
By addressing pain sooner, side effeects may be reduced, quality of life improved, and there may be cost advantages.
1. Stearns L, Boortz-Marx R, Du Pen S, Friehs G, et al. Intrathecal drug delivery fo rthe management of cancer pain: a multidisciplinary consensus of best clinical practices. J Support Oncol 2005;3(6):
2. Hassenbusch SJ. Cost modeling for alternate routes of administration of opioids for cancer pain. Oncol 1999 May;13(5 suppl 2):63-7.
3. Brogan SE. Intrathecal therapy for the management of cancer pain. Curr Pain Head Rep 2006;10:

36. Clinical Outcomes Cancer Pain Trial, 2002
Randomized
Prospective
International (5 countries)
Multicenter (21 centers)
Clinical trial of efficacy of combining IDDS (Medtronic SynchroMed® infusion system) and Comprehensive Medical Management (CMM) vs. CMM alone for patients with persistent cancer pain
The Cancer Pain Trial was an international, multicenter, randomized clinical trial designed to evaluate the clinical effectiveness of intrathecal drug delivery using the Medtronic SynchroMed® Infusion System and comprehensive medical management vs. CMM alone for patients with persistent cancer pain.
Clinical effectiveness was measured using outcomes of pain and opioid side effects. In addition to pain control, the trial also documented other outcomes, including persistence and changes in side effects over time, patient and caregiver quality of life, cost of care, and survival.
Journal of Clinical Oncology, Vol 20, No 19, October 1, 2002:

37. Conventional Medical Management Per AHCPR Guidelines
First, by mouth
By the clock, not p.r.n.
By the WHO analgesic ladder
For the individual, as pain perception is highly individual
With attention to drug titration, side effects, and patient’s assessment of pain
CMM consisted of comprehensive pain management delivered in accordance with guidelines published by the Agency for Health Care Policy and Research, an agency of the Federal Government. Patients assigned to the CMM group received all the pain therapy routinely administered at the participating cancer centers except spinally administered drugs or cordotomy. CMM included:
 Other opioids
 Other non-opioids
 Combinations of drugs
 Higher doses
 Drug therapy for opioid side effects.
Agency for Health Care Policy and Research. Management of Cancer Pain: Clinical Practice Guideline, Number 9, AHCPR Pub. No , 1994:42-45.
Agency for Health Care Policy and Research. Management of Cancer Pain: Clinical Practice Guideline, Number 9, AHCPR Pub. No , 1994:42-45.

38. Outcomes/Measures Primary Objective Measurement Methods
Efficacy:
≥20% reduction in pain VAS or
equal VAS with ≥20% reduction in mean toxicity score or
≥20% reduction in both pain VAS and toxicity 
Visual analog scale (VAS)
Common Toxicity Criteria
Composite scores from 15 measures of toxicity
Secondary Objectives
Measurement Methods
Side effects
Persistence and changes in side effects over time
Quality of life (QOL): measured for both patients and caregivers
Brief Pain Inventory
SF-12 Health Survey
Caregiver Quality of Life
Clinical endpoints in the Cancer Pain Trial included:
Primary objective endpoint – combined pain relief and opioid side effects
Effectiveness – whether or not the treatment works.
Secondary endpoints included:
Side effects – the harmful effects of a drug or treatment.
Quality of life – an assessment of the patient's and caregiver’s ability to function and cope.
Cost – how much a treatment costs.
Survival – coincidental finding, not a planned endpoint. It was monitored for safety reasons.
Resource utilization/cost
NCI-ASCO Economics Workbook
Findings
Measurement Methods
Survival
Kaplan-Meier life tables
Smith TJ, Staats PS, Deer T, Stearns LJ, et al. Randomized clinical trial of an implantable drug delivery system compared with comprehensive medical management for refractory cancer pain: Impact on pain, drug-related toxicity, and survival. J Clin Oncol. 2002;20(19):

39. Mean Reduction in VAS at 1 Month
Pain Relief
Mean Reduction in VAS at 1 Month
6.00
5.00
4.00
VAS: Mean Change
3.00
2.00
1.00
“As treated” analysis was done to better understand “as randomized” results. Five CMM patients had systems implanted and 22 IDDS patients did not.
The “as treated” reduction in mean VAS pain score, regardless of randomized assignment, was estimated by the regression model to be 1.4 points greater in patients with a pump implant than in those without (P=0.007).
Within the group randomized to IDDS, those who actually received IDDS experienced a reduction in mean pain VAS score 1.97 points larger than those who did not receive a pump (P=0.01).
0.00
CMM
IDDS
Non-
Non-
(n=72)
(n=71)
Implanted
Implanted
Implanted
Implanted
(n=89)
(n=54)
(n=22)
(n=49)
As Randomized
As Treated
IDDS As Treated
Error bars are +/- 2 standard errors
(adjusted)
(adjusted)
Smith TJ, Staats PS, Deer T, Stearns LJ, et al. Randomized clinical trial of an implantable drug delivery system compared with comprehensive medical management for refractory cancer pain: Impact on pain, drug-related toxicity, and survival. J Clin Oncol. 2002;20(19):

40. Types of Patient Pain
Approximately 75% of patients in both arms of the Cancer Pain Trial had neuropathic pain, with either pure neuropathic pain, or mixed (neuropathic-nociceptive) pain.
Neuropathic pain was much more commonly seen in patients in the Cancer Pain Trial than in many previously published studies.
Neuropathic pain is one of the primary reasons for failure of cancer pain therapy following the WHO ladder.†
†Meuser T, Pietruck C, Radbruch L, Stute P, Lehmann KL, Grond S. Symptoms during cancer pain treatment following WHO-guidelines: a longitudinal follow-up study of symptom prevalence, severity and etiology. Pain. 93: , 2001.
Smith TJ, Staats PS, Deer T, Stearns LJ, et al. Randomized clinical trial of an implantable drug delivery system compared with comprehensive medical management for refractory cancer pain: Impact on pain, drug-related toxicity, and survival. J Clin Oncol. 2002;20(19):

41. Results at 4 Weeks Clinical Success*
84.5% of IDDS patients experienced clinical success vs. 70.8% in CMM arm
Pain reduction (VAS)
 39.1% for CMM,  51.5% for IDDS
Composite toxicity (CTC)
 17.1% for CMM,  50.3% for IDDS (P=0.004)
Side effects (CTC)
Fatigue and reduced consciousness significantly less with IDDS than CMM (P<0.05)
Impotence and pruritis worsened with CMM
4 week data showed significant improvements for patients treated with IDDS over those receiving CMM only.
At 4 weeks, for CMM patients the mean VAS pain score fell from 7.81 to 4.76, a reduction of 3.05 (39.1%). For IDDS patients, the VAS pain score fell from 7.57 to 3.67, a difference of 3.90 (51.5%). The VAS change at 4 weeks was larger by 12.4% in the IDDS group, but not statistically significant (P=0.055).
The CMM group mean composite toxicity scores fell from 6.36 to 5.27, a reduction of 1.09 (17.1%), and in the IDDS group from 7.22 to 3.59, a reduction of 3.63 (50.3%). The 33.2% larger reduction in the IDDS group was statistically significant (P=0.004).
All of the measured toxicities that could be attributed to opioids and other drugs used in pain therapy were reduced more in the IDDS group than in the CMM group. Significantly larger reductions (P<0.05) in the IDDS group were noted for fatigue and reduced consciousness.
Smith TJ, Staats PS, Deer T, Stearns LJ, et al. Randomized clinical trial of an implantable drug delivery system compared with comprehensive medical management for refractory cancer pain: Impact on pain, drug-related toxicity, and survival. J Clin Oncol. 2002;20(19):
* Defined as a ≥20% reduction in VAS pain score or equal pain with a ≥20% reduced toxicity.

42. Reduction in 15 Toxicities (as randomized)
*Statistically significant (P<0.05)
Individual Toxicity
Reduction in Mean Severity
CMM
IDDS
-0.3
-0.2
-0.1
0.1
0.2
0.3
0.4
0.5
0.6
0.7
0.8
Reduced libido
Urticaria
Pruritus
Weight loss
Vomiting
Nausea
Dehydration
Constipation
Anorexia
Personality
Memory loss
Reduced level of consciousness
Confusion
Fatigue *
Impotence
Reduction occurred in all opioid side effects, not just one or two, in IDDS patients.
Significantly larger reductions (P<0.05) in the IDDS group were noted for fatigue and depressed level of consciousness/sedation.
Impotence and pruritus actually worsened in the CMM group but not in the IDDS group.
Smith TJ, Staats PS, Deer T, Stearns LJ, et al. Randomized clinical trial of an implantable drug delivery system compared with comprehensive medical management for refractory cancer pain: Impact on pain, drug-related toxicity, and survival. J Clin Oncol. 2002;20(19):

43. Serious Adverse Events
Smith TJ, Staats PS, Deer T, Stearns LJ, et al. Randomized clinical trial of an implantable drug delivery system compared with comprehensive medical management for refractory cancer pain: Impact on pain, drug-related toxicity, and survival. J Clin Oncol. 2002;20(19):

44. Cancer Pain Trial Results
Reduced pain
Reduced side effects like fatigue and sedation
Positive trend toward QOL*
This clinical study showed that intrathecal drug delivery offered advantages to individuals with severe, intractable cancer pain.
When comparing patients who received infusion therapy with those who received conventional medical management alone, the study showed those receiving infusion therapy had statistically significant decreases in composite drug toxicity scores.
Significantly more patients achieved clinical success (greater than or equal to 20% better pain relief and/or toxicity) with IDDs than with CMM alone.
All toxicities were reduced with the most significant reductions in fatigue and sedation/drowsiness. The infusion therapy group also demonstrated improved pain control.
More patients achieved clinical success with IDDS
Smith TJ, Staats PS, Deer T, Stearns LJ, et al. Randomized clinical trial of an implantable drug delivery system compared with comprehensive medical management for refractory cancer pain: Impact on pain, drug-related toxicity, and survival. J Clin Oncol. 2002;20(19):
* Based on the Brief Pain Index Interference scores

45. Medtronic Resources Patient Services
Online Resources at professional.medtronic.com
Practice Development Toolkit
Reimbursement Support
Patient Education Materials
Medtronic technical services
Monday-Friday 7:00am-6:00pm CST
Emergency technical support 7 days a week, 24 hours a day
Patient Services
Monday-Friday 8:00am-5:00pm CST
Coverage and Authorization Services
Medical Education and Training Courses
A variety of training and education opportunities to keep clinicians current with pain therapies
Talk to your local Medtronic representative or visit professional.medtronic.com
Local Medtronic Representative

46. SynchroMed® II Drug Infusion System
Please refer to the product disclosure for complete product
details.
Enclose or attach the SynchroMed II System disclosure with lecture handouts.

47. SynchroMed® II Drug Infusion System Brief Summary
Product technical manuals and the appropriate drug labeling must be reviewed prior to use for detailed disclosure.
Indications:
US: Chronic intraspinal (epidural and intrathecal) infusion of preservative-free morphine sulfate sterile solution in the treatment of chronic intractable pain, chronic intrathecal infusion of preservative-free ziconotide sterile solution for the management of severe chronic pain, and chronic intrathecal infusion of Lioresal® Intrathecal (baclofen injection) for the management of severe spasticity; chronic intravascular infusion of floxuridine (FUDR) or methotrexate for the treatment of primary or metastatic cancer. Outside of US: Chronic infusion of drugs or fluids tested as compatible and listed in the product labeling.
Contraindications:
Infection; implant depth greater than 2.5 cm below skin; insufficient body size; spinal anomalies; drugs with preservatives, drug contraindications, drug formulations with pH < 3, use of catheter access port (CAP) kit for refills or of refill kit for catheter access, blood sampling through CAP in vascular applications, use of Personal Therapy Manager to administer opioid to opioid-naïve patients or to administer ziconotide.
Warnings:
Non-indicated formulations may contain neurotoxic preservatives, antimicrobials, or antioxidants, or may be incompatible with and damage the system. Failure to comply with all product instructions, including use of drugs or fluids not indicated for use with system, or of questionable sterility or quality, or use of non-Medtronic components or inappropriate kits, can result in improper use, technical errors, increased risks to patient, tissue damage, damage to the system requiring revision or replacement, and/or change in therapy, and may result in additional surgical procedures, a return of underlying symptoms, and/or a clinically significant or fatal drug under- or overdose. Refer to appropriate drug labeling for indications, contraindications, warnings, precautions, dosage and administration information, screening procedures and underdose and overdose symptoms and methods of management. Physicians must be familiar with the drug stability information in the product technical manuals and must understand the dose relationship to drug concentration and pump flow rate before prescribing pump infusion. Implantation and ongoing system management must be performed by individuals trained in the operation and handling of the infusion system. An inflammatory mass that can result in serious neurological impairment, including paralysis, may occur at the tip of the implanted catheter. Clinicians should monitor patients on intraspinal therapy carefully for any new neurological signs or symptoms, change in underlying symptoms, or need for rapid dose escalation.
Inform patients of the signs and symptoms of drug under- or overdose, appropriate drug warnings and precautions regarding drug interactions, potential side effects, and signs and symptoms that require medical attention, including prodromal signs and symptoms of inflammatory mass.

48. SynchroMed® II Drug Infusion System Brief Summary, Continued
Failure to recognize signs and symptoms and seek appropriate medical intervention can result in serious injury or death. Instruct patients to notify their healthcare professionals of the implanted pump before medical tests/procedures, to return for refills at prescribed times, to carry their Medtronic device identification card, to avoid manipulating the pump through the skin, to consult with their clinician if the pump alarms and before traveling or engaging in activities that can stress the infusion system or involve pressure or temperature changes. Strong sources of electromagnetic interference (EMI), such as short wave (RF) diathermy and MRI, can negatively interact with the pump and cause heating of the implanted pump, system damage, or changes in pump operation or flow rate, that can result in patient injury from tissue heating, additional surgical procedures, a return of underlying symptoms, and/or a clinically significant or fatal drug underdose or overdose. Avoid using shortwave (RF) diathermy within 30 cm of the pump or catheter. Effects of other types of diathermy (microwave, ultrasonic, etc.) on the pump are unknown. Drug infusion is suspended during MRI; for patients who can not safely tolerate suspension, use alternative drug delivery method during MRI. Patients receiving intrathecal baclofen therapy are at higher risk for adverse events, as baclofen withdrawal can lead to a life threatening condition if not treated promptly and effectively. Confirm pump status before and after MRI. Reference product labeling for information on sources of EMI, effects on patient and system, and steps to reduce risks from EMI.
Precautions:
Monitor patients after device or catheter replacement for signs of underdose/overdose. Infuse preservative-free (intraspinal) saline or, for vascular applications, infuse heparinized solutions therapy at minimum flow rate if therapy is discontinued for an extended period of time to avoid system damage. EMI may interfere with programmer telemetry during pump programming sessions. EMI from the SynchroMed programmer may interfere with other active implanted devices (e.g., pacemaker, defibrillator, neurostimulator).
Adverse Events:
Include, but are not limited to, spinal/vascular procedure risks; infection; bleeding; tissue damage, damage to the system or loss of, or change in, therapy that may result in additional surgical procedures, a return of underlying symptoms, and/or a clinically significant or fatal drug underdose or overdose, due to end of device service life, failure of the catheter, pump or other system component, pump inversion, technical/programming errors, or improper use, including use of non-indicated formulations and/or not using drugs or system in accordance with labeling; pocket seroma, hematoma, erosion, infection; post-lumbar puncture (spinal headache); CSF leak and rare central nervous system pressure-related problems; hygroma; radiculitis; arachnoiditis; spinal cord bleeding/damage; meningitis; neurological impairment (including paralysis) due to inflammatory mass; potential serious adverse effects from catheter fragments in intrathecal space, including potential to compromise antibiotic effectiveness for CSF infection; anesthesia complications; body rejection phenomena; local and systemic drug toxicity and related side effects; potential serious adverse effects from catheter placement in intravascular applications.
USA Rx Only Rev 0809

49. Questions?