3/4/2011

Faculty Disclosures

Managing Challenging Cancer Pain Issues in the Outpatient Setting

David S. Craig, PharmD, BCPS H. Lee Moffitt Cancer Center and Research Institute Tampa, Florida HOPA Annual Conference, Salt Lake City, UT March 24th & 25th 2011

David Craig had no areas of conflict to disclose

Presentation Outline
Discuss the treatment options and appropriate monitoring parameters for challenging cancer pain patients
Describe available risk assessment tools used to stratify opioid abuse potential Describe future variables that may influence current pain management strategies

Learning Objective

Discuss the treatment options and appropriate monitoring parameters for challenging cancer pain patients

Patient Case
JW is a 37 y/o male with hx of SCC* of the glottis Received XRT and chemotherapy in 2009 followed by total laryngectomy in Jan 2011 Patient was also given a g-tube for meds/feeds Referred to outpatient Palliative Care Clinic for pain management Social hx

Patient case (cont)

While hospitalized transitioned from
Oxycodone CR 160 mg q 6 hrs, oxycodone prn to Methadone solution 20 mg q 6 hrs and oxycodone
solution 60mg q 3 hrs prn

Adjuvants

Pregabalin 50mg po q 12 hrs

Laboratory values

+ smoking 1-2 pack per day x ? years + social alcohol use + Heroin abuse in past, no recent per patient Completed rehab program for heroin addiction

QTc while on methadone 499, 482, 472 msec Other lab values normal

*SCC squamous cell carcinoma

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Pain/Symptom Assessment
Patient reporting pain 9/10 in neck, not controlled with current regimen Describes pain as sharp, stabbing, burning and constant Patient reports some benefit from methadone but requesting oxycodone CR Mild nausea/vomiting controlled with oral antiemetics (metoclopramide)

My Recommendations
Use methadone in place of oxycodone CR

? Less abuse potential Potential cost savings, but prolonged QTc!

Because of neuropathic pain features

Pregabalin 50mg po 12 hrs Tricyclic antidepressants another option +/ NSAID and/or APAP likely to be helpful Could consider dexamethasone

Methadone Pearls
ECG recommended in following cases

Risk Assessment Tools

Opioid Risk Tool (ORT)

At baseline for any high risk patients (i.e. at

risk for TDP)

Concomitant QT prolonging drugs, or

significant d/d interactions Doses >100mg/day, or if IV is used Electrolyte abnormalities If current QTc >450msec but < 500msec, monitor more frequently, if >500msec watch out!
Krantz M, et al. Ann Intern Med 2009;150:387-395

Current Opioid Misuse Measure (COMM)

Screener and Opioid Assessment for Patients with Pain-Revised (SOAPP-R)

Opioid Risk Tool (ORT)

5-question screening tool used to predict opioid related aberrant behavior

COMM
Current Opioid Misuse Measure (COMM)

17 item questionnaire, 5-point Likert scale A quick and easy to administer patient-self assessment Validated in approximately 500 patients Ideal for documenting decisions about the level of monitoring planned for a particular patient or justifying referrals to specialty pain clinic Evaluates behaviors within the past 30 days Scored by adding sum of responses of patients reponses to questions (0 =never to 4 = very often) Score of 9 or higher is considered a positive
Found at http://www.painedu.org, Accessed on Feb 2, 2011. 2011 Inflexxion, Inc, Used with permission

Family history of substance abuse (M>F) Personal history of substance abuse Age (16-45), younger more predictive History of preadolescent sexual abuse (F only) Psychological disease

Total score risk category

Low Risk 0 3 Moderate Risk 4 7 High Risk > 8

Webster LR, Webster RM. Pain Med. 2005 Nov-Dec;6(6):432-42

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SOAPP-R
Screener and Opioid Assessment for Patients with PainRevised (SOAPP-R) 24 item questionnaire, 5-point Likert scale A quick and easy to administer patient-self assessment Validated in approximately 500 patients Scored by adding sum of responses of patients reponses to questions (0 =never to 4 = very often) Score of 18 or higher is considered positive (high risk) Moderate risk = 10 to 21 Low risk < 9

Patient Case-Risk Stratification

ORT = 8 (High Risk)

Personal history of substance abuse

Alcohol (3 points) Illegal drugs heroin (4 points)

Age 16 45 (1 point)
COMM and SOAPP-R not conducted, but likely also positive/high risk

Found at http://www.painedu.org, Accessed on Feb 2, 2011. 2011 Inflexxion, Inc. Used with permission

Now What?
Screening tools are just that Potential strategies for high risk patients Frequent office visits Random urine drug screening Patient-provider agreements Less abusable formulations should be considered May require addictionologist/specialist consultation Family members can be helpful Maximize adjuvants/co-analgesics Lower quantities of rxs dispensed

Monitoring Parameters
Opioids
Constipation, sedation, lethargy Monitor AST/ALT
Oxycodone, Hydrocodone, Methadone, Fentanyl, Buprenorphine

Renal function (BUN/Scr)

Morphine, Codeine, Tramadol, Levorphanol, Hydromorphone

ECG (QT/QTc)
Methadone, Buprenorphine, Propoxyphene

Monitoring Parameters
Other analgesics
NSAID/Corticosteroids
GI bleeding, renal, cardiovascular risks

Available Resources
Opioid REMS Likely to be finalized in early 2011 Cancer Pain Management American Pain Society (www.ampainsoc.org)
Guideline for the Management of Cancer Pain in Adults and Children NCCN (www.nccn.org) NCI (www.cancer.gov)

Antiepileptics
AST/ALT and Scr where appropriate

Tricyclic antidepressants
Anticholinergic side effects, QT prolongation, suicide risk CYP 2D6 d/d interactions

SNRIs (venlafaxine, duloxetine, milnacipran)

AST/ALT Suicide risk Anticholinergic side effects, other serotonergic agents

Other non-cancer guidelines Washington state Oklahoma state Canadian guidelines

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REMS
Risk Evaluation and Mitigation Strategies To ensure benefits outweigh the risks Elements

Opioid REMS
Currently approved
Abstral (fentanyl) Butrans (buprenorphine) Darvocet (propoxyphene/apap) Exalgo (hydromorphone ER) Morphine solution (10mg/5mL, 20mg/mL) Onsolis (fentanyl) Oxycodone solution (20mg/mL) Oxycontin (oxycodone CR) Suboxone (buprenorphine/naloxone) Tapentadol

Timetable for submission of REMS

assessments

Medication guide/PI Communication plan Elements to assure safe use (ETASU)

http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/GuidancesUCM184128.pdf

http://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/ucm111350.htm

Washington State Guidelines

State of WA recently adopted treatment guidelines for noncancer pain management Currently excludes Acute pain, pain at the end of life (hospice) Cancer pain Requires that patients on MEDD* > 120 mg/day be evaluated by a pain specialist

Similar Guidelines
States with similar policies in place Utah Clinical Guidelines on Prescribing Opioids
http://health.utah.gov/prescription/pdf/Utah_guidelines_pdfs.pdf

Oklahoma Guidelines for Prescription of Opioid

Medications for Acute and Chronic Pain
http://www.owcc.state.ok.us/PDF/Guidelines%20for%20the%20Prescription%20of %20OpioId%20Medications%20rev%2011-01-07%20COMPLETE.pdf

In addition

Having one physician prescribe opioids Use of a single pharmacy for a patient to fill his prescriptions Use of opioid treatment agreements between the physician

and patient to clearly define patient and physician responsibilities Assessment of risks of developing addiction by conducting a thorough history including any history of substance abuse before starting treatment
http://www.agencymeddirectors.wa.gov/Files/AGReportFinal.pdf *MEDD = Morphine Equivalent Daily Dose

Canadian Guidelines for Safe and Effective Use of Opioids for Chronic Non-Cancer Pain

http://nationalpaincentre.mcmaster.ca/opioid/index.html

Conclusions
Cancer patients with pain have risks too! Risk stratification and risk minimization should be employed for all patients Dont be fooled by patients with cancer pain and its treatments Always remember adjuvants, other alternatives, outcomes, treatment plans Although opioids remain mainstay, think outside the box when necessary

Questions
1. Is this patient at risk of opioid abuse/misuse? 2. How could you stratify patient abuse risk?
a) ORT b) COMM c) SOAPP

3. Is methadone the best analgesic? 4. What are the appropriate monitoring parameters for this patient?

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Faculty Disclosures

Management of Radiation Induced Toxicity in the Outpatient Setting

Makala Pace, PharmD, BCOP Clinical Pharmacy Specialist The University of Texas MD Anderson Cancer Center Salt Lake City, Utah

Makala Pace had no areas of conflict to disclose

Objective
Identify treatment options and appropriate monitoring parameters for radiationinduced toxicities in an outpatient setting

History of Radiation (XRT)

1895 Wilhelm Roentgen

Photographic image of
the human hand

1896 Emil Grubbe

Therapeutic use for

advanced ulcerated breast cancer

Lawrence TS et al. In: DeVita VT et al., eds. Cancer: Principles and Practice of Oncology. 8th ed. 2008:307. http://www.calstatela.edu/faculty/kaniol/f2000_lect_nuclphys/lect1/roentgen.htm

Types of Radiation Used to Treat Cancer

Photons

Administration
External beam radiation most widely used

X-rays and gamma rays

Particle Radiation

Electrons, protons, neutrons, alpha

particles, beta particles

3-dimensional conformal radiation therapy Intensity-modulated radiation therapy Stereotactic radiation therapy/surgery Proton therapy

Internal radiation

Brachytherapy
Systemic radiation therapy

Radiopharmaceuticals
Choice depends upon multiple variables
Radiation Therapy Principles. American Cancer Society website. http://www.cancer.org http://www.chesapeakepotomaccancer.com Radiation Therapy Principles. American Cancer Society website. http://www.cancer.org Radiation Therapy for Cancer Fact Sheet. National Cancer Institute website. http://www.cancer.gov

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Cancers Treated with Radiation

Skin CNS Head and neck Thoracic

Cancers Treated with Radiation

Urinary tract Lymphomas

Eye and orbit Nasopharynx Nasal/paranasal Salivary gland Oral cavity Oropharynx Hypopharynx Larynx Thyroid

Lung Mediastinum Esophageal

Breast Gastrointestinal

Kidney Bladder
Male GU

Non-Hodgkin's Hodgkins Cutaneous T-cell

Sarcomas

Prostate Testicular
Gynecologic

Bone and soft tissue

Metastatic disease

Stomach Pancreatic Liver Colon and rectum Anal

Cervical Endometrial Ovarian

Brain, spinal cord Bone Visceral recurrence

In: Halperin EC et al eds. Perez and Bradys Principles and Practice of Radiation Oncology. 5th ed. 2008

In: Halperin EC et al eds. Perez and Bradys Principles and Practice of Radiation Oncology. 5th ed. 2008

Radiation Toxicity
Development is multi-factorial

Radiation-Induced Toxicity
Acute

Area of body treated Dose given per day Total dose given Patients performance status Concomitant therapy

Occur during treatment

Sub-Acute

Occur 2 weeks to 3 months after therapy

Chronic

Occurs 6 or more months after a course of

radiation

Radiation Therapy for Cancer Fact Sheet. National Cancer Institute website. http://www.cancer.gov

Radiation Therapy for Cancer Fact Sheet. National Cancer Institute website. http://www.cancer.gov Lawrence TS et al. In: DeVita VT et al., eds. Cancer: Principles and Practice of Oncology. 8th ed. 2008:307.

Skin: Radiation Dermatitis

Grade 1 Grade 2
Moderate to brisk erythema; patchy moist desquamation, mostly confined to skin folds and creases; moderate edema

Faint erythema Dry desquamation

Management of Radiation-Induced Toxicity

Grade 3
Moist desquamation other than skin folds and creases; bleeding induced by minor trauma or abrasion

Grade 4
Skin necrosis or ulceration of full thickness of dermis; spontaneous bleeding from involved site; skin graft indicated

http://www.omicsonline.org/ArchiveJCST/2009/December/03/JCST1.28.php http://emedicine.medscape.com/article/911711-overview http://content.onlinejacc.org/cgi/powerpoint/jacc;44/11/2259/FIG1?view=true&filename=jaccv44i11p2259FIG1.ppt National Cancer Institute. Common Terminology Criteria for Adverse Events Version 4.0 http://www.thefullwiki.org/Peeling_skin

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Radiation Dermatitis
Toxicity Treatment Nonionic moisturizers TID (Cetaphil, Aveeno, Lubriderm)

Biafine Topical Emulsion

Apply a generous amount three times per day, seven days a week gently massaging the area until it is completely absorbed Continue to apply until the skin has fully recovered Do not apply 4 hours prior to a radiation session
http://www.biafine.com

Grade 1

Hydrocortisone 1% cream TID PRN

Biafine Topical Emulsion TID Grade 2 and Grade 3 Normal saline or modified Burows solution compresses Polymixin B/ Neomycin cream TID Hydrogel protective wound dressing

Nicolaou N. Cancer Management: A Multidisciplinary Approach. 10th ed. 2007. National Cancer Institute. Common Terminology Criteria for Adverse Events Version 4.0

Hydrogels
Rehydrates necrotic and sloughy wounds and provides a moist wound healing environment
Generally are clear, viscous gels that protect the wound from desiccating

Radiation Dermatitis
Toxicity Treatment
Exclude and treat infection Normal saline or modified Burow s solution compresses Grade 4 Debridement of tissue Flexible hydroactive hydrocolloid dressings Vitamin E 300 to 1000 units PO per day and pentoxifylline 400 mg PO BID - TID

Should be used as a primary wound dressing choice in wounds that are substantially or fully granulated
Multiple products available from multiple manufacturers Tegagel, DuoDERM
SAF-Gel, NU-GEL, DermaSyn

Chronic changes

Moisturizers, sunblock/sunscreen

http://www.medicaledu.com/hydroghp.htm

Nicolaou N. Cancer Management: A Multidisciplinary Approach. 10th ed. 2007. National Cancer Institute. Common Terminology Criteria for Adverse Events Version 4.0

Hydrocolloid Dressings
Help the wound to autolytically debride itself Removed without tearing the granulation tissue underneath Best applied to wounds that produce light to medium exudate or transudate. May remain in place for 3 to 4 days, sometimes longer
http://www.medicaledu.com/hydrochp.htm

Radiation Dermatitis: Tips

Protect the affected area Keep it clean Avoid sun exposure Avoid scratching Avoid irritants
Different areas may require different approaches to treatment Influenced by concomitant therapy Dont apply lotions, gels, etc. shortly before XRT Gently clean and dry skin prior to each XRT dose
Bernier J et al. Ann Oncol. 2008;19:142-9.

Multiple products available from multiple manufacturers

Tegasorb, DuoDERM, NUDERM, DermaFilm HD

Disadvantages Not to be applied over infected wounds Can develop a foul odor after having been applied for 2-4 days

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Oropharynx
Side Effect Treatment Saline/bicarbonate, other electrolyte solution QID (Caphosol) Mucositis Lidocaine/diphenhydramine/simethicone 5-10 mL QID PRN Systemic analgesics PRN Antifungals Protective barriers (sulcralfate, Gelclair ) Time (may take up to 4 months for regeneration) Dysgeusia Zinc sulfate 45 mg PO TID Amifostine 500 mg IV weekly (H&N only)
Hovan AJ. Supp Care Cancer. 2010;18:1081-97. http://emedicine.medscape.com/article/1079570-overview Nicolaou N. Cancer Management: A Multidisciplinary Approach. 10th ed. 2007.

Caphosol
(supersaturated calcium phosphate rinse)
Electrolyte solution that resembles human saliva Moisten, lubricate and clean the oral cavity, loosen mucus Mix two ampules together, swish with the solution for 1 minute, spit out and repeat with other of solution Use 4 to 10 times daily

http://www.caphosol.com

Gelclair Bioadherent Oral Gel

Works by forming a barrier that protects the nerve endings that cause pain Pour packet into a glass and add 1 tablespoon of water Stir then rinse around the mouth for at least 1 minute or as long as possible, gargle and spit out Use 3 times a day or as needed Do not eat or drink for at least 1 hour following use
http://www.gelclair.com

Oropharynx
Side Effect Caries Treatment Prevention is key dental oncology Extractions of potential problem teeth in radiation field Fluoride gels (tray application)

http://ocw.tufts.edu/Content/51/lecturenotes/551485/551662 Nicolaou N. Cancer Management: A Multidisciplinary Approach. 10th ed. 2007. http://www.nidcr.nih.gov/OralHealth/Topics/CancerTreatment/ReferenceGuideforOncologyPatients.htm

Esophagus
Side Effect Treatment Lidocaine/diphenhydramine/simethicone 5-10 mL QID Esophagitis Systemic analgesics PRN Nutritional support Protective barrier sucralfate Acid suppressants PPIs, H1 blockers, H2 blockers Xerostomia Side Effect Parotitis/Siladenitis

Salivary Glands
Treatment Aspirin or NSAIDs

Pilocarpine 5 mg PO TID to QID

Artificial saliva Amifostine 200 mg/m2 IV daily prior to XRT Cevimeline 30 mg PO TID Papain enzyme (not available in U.S.) Thick Saliva Guaifenesin Scopolamine patch

Nicolaou N. Cancer Management: A Multidisciplinary Approach. 10th ed. 2007. http://www.med.uottawa.ca/students/md/blockorientation/assets/img/gastro/Reflux_Esophagitis.jpg

Nicolaou N. Cancer Management: A Multidisciplinary Approach. 10th ed. 2007.

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Ears & Mandible

Side Effect Otitis externa Serous otitis media Temporomandibular joint fibrosis Osteoradionecrosis Treatment Side Effect

Genitourinary
Treatment Phenazopyridine 100 -200 mg PO TID PRN dysurea Acute cystitis Oxybutynin 5 mg PO TID PRN frequency/urgency Oxybutynin 5 mg PO TID PRN Obstructive urinary symptoms Tamsulosin 0.4 mg PO daily Finasteride 5 mg PO daily Terazosin or doxazosin 1-2 mg PO daily

Hydrocortisone/neomycin/polymyxin B ear drops TID

Decongestants, phenylephrine otic solution Daily stretching exercises Complete any dental work (extractions) before XRT; eliminate infection; pentoxifylline

Nicolaou N. Cancer Management: A Multidisciplinary Approach. 10th ed. 2007.

Nicolaou N. Cancer Management: A Multidisciplinary Approach. 10th ed. 2007.

Bowel
Side Effect Treatment Low-residue diet Loperamide or diphenoxylate 1-2 tabs PO QID PRN diarrhea Diarrhea Exclude Clostridium difficile infection Cholestyramine 4-8 gram PO QID Octreotide 0.1 mg SQ TID Hemorrhoidal preparations with hydrocortisone TID prn (ointment or suppositories) Glucocorticoid retention enemas Mesalamine suppositories
Nicolaou N. Cancer Management: A Multidisciplinary Approach. 10th ed. 2007.

Case
A 64 yr-old male with H&N cancer is two weeks into his 7 week course of radiation therapy. He comes to clinic for an interval check, and upon examination has grade 1 radiation dermatitis (dry desquamation).

Proctitis

Audience Response Question

What management strategy would be appropriate at this time?
1. Debridement of tissue, treatment with systemic
antibiotics, and use of hydroactive hydrocolloid dressings 2. Topical antibiotics, and hydrogel wound dressings 3. Biafene topical emulsion, topical hydrocortisone, and nonionic moisturizers 4. Moisturizers and sunblock