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Home , Antiemetic, Mucositis

6/16/2015

DISCLOSURES

● Leah Edenfield declares no conflicts of interest, real or apparent, TOXICITY AND and no financial interests in any company, product, or service SUPPORTIVE CARE: mentioned in this program, including grants, employment, gifts, MANAGEMENT OF stock holdings, and honoraria. GASTROINTESTINAL SYMPTOMS

Leah Edenfield, PharmD, BCPS PGY2 Oncology Pharmacy Resident

June 12, 2015

OBJECTIVES

 Identify gastrointestinal effects frequently associated with chemotherapy

 Design a strategy to prevent chemotherapy-induced and and to manage breakthrough symptoms

 Recommend over-the-counter for and NAUSEA AND VOMITING as well as treatments for refractory symptoms

 Evaluate appetite for oncology patients

 Select appropriate therapy for management of mucositis

PATHOPHYSIOLOGY CONTRIBUTING CAUSES

 Impulses to the vomiting center come from the chemoreceptor trigger zone, pharynx and GI tract, and cerebral cortex   Impulses are then sent to the salivation center, abdominal muscles,  Vestibular dysfunction respiratory center, and cranial nerves  Hypercalcemia, hyperglycemia, or hyponatremia   Opiates or other concomitant mediations  Gastroparesis  Anxiety

and receptors are involved in the emetic response and are activated by chemotherapy  Other relevant receptors include acetylcholine, , histamine, , opiate, and neurokinin-1 receptors in the vomiting and vestibular centers Antiemesis. NCCN Guidelines. Version 1.2015. Antiemesis. NCCN Guidelines. Version 1.2015. Image available at www.aloxi.net

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EMETIC RISK OF CHEMOTHERAPY ASCO GUIDELINES: EMETIC RISK

 Emetic risk categories .High (>90%) .Moderate (30-90%) .Low (10-30%) .Minimal (<10%)

*Anthracycline + cyclophosphamide = high risk American Society of Clinical Oncology 2011. www.asco.org/guidelines/antiemetics. American Society of Clinical Oncology 2011. www.asco.org/guidelines/antiemetics.

ASCO GUIDELINES: MANAGEMENT ASCO GUIDELINES: MANAGEMENT

High Risk  Breakthrough nausea and vomiting despite appropriate

•NK1 antagonist: 150mg or 125mg day 1 and 80mg prophylaxis days 2-3 •5-HT3 receptor antagonist day 1 . Add or alprazolam • 12mg day 1 and 8mg days 2-3 or 2-4 . Add Moderate Risk . Substitute for 5-HT3 receptor antagonist

• 0.25g IV or 0.5g PO day 1 (alternatively may use another 5-HT3 . Add receptor antagonist ) •Dexamethasone 8mg IV or PO days 1-3

Low Risk

•Dexamethasone 8mg

Minimal Risk

•No routine antiemetic

American Society of Clinical Oncology 2011. www.asco.org/guidelines/antiemetics. American Society of Clinical Oncology 2011. www.asco.org/guidelines/antiemetics.

NCCN GUIDELINES: HIGH EMETIC RISK NCCN GUIDELINES: MODERATE RISK

Aprepitant- - Olanzapine- Aprepitant- Netupitant- Olanzapine- containing regimen containing regimen containing regimen containing regimen containing regimen containing regimen •Aprepitant 125mg PO •Netupitant 300mg/ •Olanzapine 10mg PO •5-HT3 antagonist AND • Netupitant 300mg/ • Olanzapine 10mg PO day 1 and 80mg PO day palonosetron 0.5mg PO days 1-4 dexamethasone day 1 palonosetron 0.5mg PO days 1-3 2-3 once •Palonosetron 0.25mg IV •5-HT3 antagonist OR once • Palonosetron 0.25mg IV OR Fosaprepitant • Dexamethasone 12mg once dexamethasone days 2-3 • Dexamethasone 12mg once PO/IV day 1 and 8mg 150mg IV once PO/IV day 1 and 8mg • Dexamethasone 20mg • With or without • Dexamethasone 20mg IV PO/IV days 2-4 aprepitant or PO/IV days 2-3 once •5-HT3 antagonist day 1 IV once fosaprepitant then • Dexamethasone days 1- dexamethasone days 2-3 4

Antiemesis. NCCN Guidelines. Version 1.2015. Antiemesis. NCCN Guidelines. Version 1.2015.

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EMETOGENIC POTENTIAL OF ORAL NCCN GUIDELINES: LOW RISK AGENTS: MODERATE TO HIGH

 Dexamethasone 12mg PO/IV daily OR Class  Metoclopramide 10-40mg PO/IV then every 4-6h prn OR Tyrosine kinase inhibitors Ceritinib Crizotinib  10mg PO/IV then every 6h prn OR Lenvatinib  5-HT3 antagonist Alkylating agents (≥4mg/day) . 100mg PO daily Cyclophosphamide (≥100mg/m2/day) . 1-2mg PO daily Estramustine . 8-16mg PO daily (>75mg/m2/day) Procarbazine Lomustine Altretamine Other Etoposide Mitotane Olaparib Panobinostat Antiemesis. NCCN Guidelines. Version 1.2015. Vismodegib Antiemesis. NCCN Guidelines. Version 1.2015.

EMETOGENIC POTENTIAL OF ORAL NCCN GUIDELINES: ORAL AGENTS: MINIMAL TO LOW CHEMOTHERAPY EMESIS PREVENTION

Class Drug Class Drug Class Drug  High to moderate risk Tyrosine Afatinib Alkylating agents Melphalan Other Bexarotene kinase Axitinib Busulfan Everolimus . Start 5-HT3 antagonist before chemotherapy and continue inhibitors (<4mg/day) Bosutinib Hydroxyurea daily Chlorambucil Dasatinib Idelalisib Temozolomide Tretinoin Erlotinib (≤75mg/m2/day) Palbociclib  Low to minimal risk Cabozantinib Cyclophosphamide Imatinib (<100mg/m2/day) Topotecan . PRN recommended Lapatinib Vorinostat Mercaptopurine . Start antiemetic before chemotherapy and continue daily if Nilotinib Thioguanine nausea or vomiting occurs Ibrutinib Fludarabine Trametinib . Metoclopramide prn Capecitabine Vemurafenib Methotrexate . Prochlorperazine prn Pazopanib Immunomodulators Lenalidomide . prn Ponatinib Pomalidomide Regorafenib . 5-HT3 antagonist prn Ruxolitinib Sorafeib Antiemesis. NCCN Guidelines. Version 1.2015. Sunitinib Antiemesis. NCCN Guidelines. Version 1.2015.

NCCN GUIDELINES: ANTICIPATORY NCCN GUIDELINES: BREAKTHROUGH NAUSEA/VOMITING

 Olanzapine 10mg PO daily for 3 days  Behavioral therapy  Lorazepam 0.5-2mg PO/SL/IV q6h  /acupressure  5-10mg PO q3-6h  therapy  Haloperidol 0.5-2mg PO/IV q4-6h . Alprazolam 0.5-1mg or lorazepam 0.5-2mg PO  patch q72h . Night before treatment and repeated 1-2h before  Prochlorperazine 25mg PR q12h or 10mg PO/IV q6h chemotherapy  25mg PTR q6h or 12.5-25mg PO/IV every 4-6h  Dexamethasone 12mg PO/IV daily  Dolasetron 100mg PO daily  Granisetron 1-2mg PO daily or 1mg PO bid or 0.01mg/kg IV daily  Ondansetron 16mg PO/IV daily

Antiemesis. NCCN Guidelines. Version 1.2015. Antiemesis. NCCN Guidelines. Version 1.2015.

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ETIOLOGY

 Causes of constipation in patients . Diet . Inadequate fluid intake or fiber intake . Lack of exercise . The tumor itself . Drug therapy CONSTIPATION . Comorbidities such as organ failure, decreased mobility, and depression . Environmental factors

National Cancer Institute. http://www.cancer.gov/about-cancer/treatment/side-effects/constipation/gi-complications-hp-pdq#section/all

DRUGS AND CONSTIPATION CHEMOTHERAPY AND CONSTIPATION

 May be the result of autonomic neuropathy causing decreased

Phenothiazines motility  Inflammatory neuropathy has been demonstrated with

Anticholinergics ipilimumab  associated with chemotherapy-induced constipation . Vinca alkaloids (vinblastine, vincristine, vinorelbine) . Taxanes (paclitaxel, docetaxel, cabazitaxel) Iron supplements . Thalidomide . Cisplatin  Can be exacerbated by concomitant use

Chemotherapy Constipation

National Cancer Institute. http://www.cancer.gov/about-cancer/treatment/side-effects/constipation/gi-complications-hp-pdq#section/all Gibson RJ, Keefe DMK. Support Care Cancer 2006;14:890-900. Shailender B, Huber B, Upton MP et al. J Immunother. 2009;32:203-5. PashankarP, Season JH, McNamara J et al. J Pediatr Hematol Oncol 2011;33:e300-3. National Cancer Institute. http://www.cancer.gov/about-cancer/treatment/side-effects/constipation/gi-complications-hp-pdq#section/all

NONPHARMACOLGIC MANAGEMENT DRUG THERAPY

 Increase dietary fiber  Opioid-induced constipation . Fruit . Prevent with and stool softener (e.g., senna 8.6mg and . Green, leafy vegetables docusate 50mg two tablets daily) . Whole grains . If patient experiences constipation, increase dose and add agent  Increase fluid intake . Miralax 17g . Milk of magnesia  Exercise regularly  Avoid rectal agents in cancer patients at risk for thrombocytopenia, neutropenia, or mucositis

 Lactulose has been successful in vincristine-induced constipation

National Cancer Institute. http://www.cancer.gov/about-cancer/treatment/side-effects/constipation/gi-complications-hp-pdq#section/all National Cancer Institute. http://www.cancer.gov/about-cancer/treatment/side-effects/constipation/gi-complications-hp-pdq#section/all Harriis AC, Jackson JM.. Med J Aust. 1977;2:573-4.

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Mechanism Onset Precautions Dose Bulk Hold water in GI 12-24h, up Hydrate, avoid in Methylcellulose 5-20ml tid producers tract, soften to 72h obstruction Psyllium 1 tbsp 1-3 times stool daily NCCN GUIDELINES: PREVENTION Saline High osmolarity 0.5-3h May alter fluid and Milk of magnesia 10-20ml pulls water into electrolyte balance conc or 15-30ml regular, intestines magnesium citrate 240ml  Increase fluids and dietary fiber Stimulant Increase motor 6-10h May cause cramping, Senna 2 tablets, bisacodyl  Exercise laxatives activity of dependency 10-15mg PO or 10mg PR bowels  Prophylactic stimulant +/- stool softener Lubricant Lubricate 6-8h Aspiration potential, oil 5-30ml at bedtime  Titrate up with goal of 1 non-forced bowel movement laxatives intestinal prevents absorption of mucosa oil-soluble drugs every 1-2 days Stool Promote water 3 days Increases mineral oil Docusate sodium 50-240mg softeners retention absorption Lactulose Increases 24-48h Diarrhea from 15-30ml (10-20g) daily osmotic excessive amount, pressure avoid in obstruction Polyethylene Osmotic agent 24-96h Avoid in bowel 17g dissolved in 4-8 oz glycol obstruction beverage Opioid Reverses opioid 0.5-4h Contraindicated in Methylnaltrexone 0.15 mg/kg antagonists effect in GI tract obstruction SubQ . NCCN Guidelines. Version 2.2015. National Cancer Institute. http://www.cancer.gov/about-cancer/treatment/side-effects/constipation/gi-complications-hp-pdq#section/all

NCCN GUIDELINES: PERSISTENT NCCN GUIDELINES: INITIAL TREATMENT SYMPTOMS

 Add and titrate bisacodyl 10-15mg daily to tid  Bisacodyl suppository daily – bid  Impaction  Polyethylene glycol (Miralax)  Glycerine suppository +/- mineral oil and  Lactulose 30-60mg bid-qid disimpaction  Sorbitol 30mg every 2h x3 doses  Rule out obstruction  Magnesium hydroxide 30-60ml daily-bid  Treat other possible causes  Magnesium citrate 8 oz daily  Consider methylnaltrexone for opioid-induced constipation 0.15mg/kg subcutaneously every other day  Tap water enema

Palliative Care. NCCN Guidelines. Version 2.2015. Palliative Care. NCCN Guidelines. Version 2.2015.

INTRODUCTION

 Rates of 50-80% with some chemotherapy agents such as fluoropyrimidines and irinotecan

 Overall incidence of 14% in patients undergoing treatment for cancer

DIARRHEA  Diarrhea may be severe and life-threatening, with deaths from fluorouacil-induced diarrhea reported in 1-5% of patients in clinical trials

National Cancer Institute. http://www.cancer.gov/about-cancer/treatment/side-effects/constipation/gi-complications-hp-pdq#section/all Andreyev J, Ross P, Donnellan C et al. Lancet Oncol 2014;15;e447-60.

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PATHOPHYSIOLOGY ETIOLOGY

 Likely multifactorial  Chemotherapy  Irinotecan-induced diarrhea has a secretory mechanism with  Surgery an exudative component, was also identified  Radiation  depletion may contribute to compromise of the  therapy intestinal mucosa  Stress and anxiety  Dihydropyrimidine dehydrogenase (DPD) deficiency  (such as C. diff) . Enzyme that catabolizes 5-FU  Graft-versus-host-disease . Increased toxicity in deficiency  Cancer-related  Gilbert’s syndrome . UGT1A1*28 mutation . Reduced ability to conjugate and secrete SN-38 . Increased irinotecan toxicity

National Cancer Institute. http://www.cancer.gov/about-cancer/treatment/side-effects/constipation/gi-complications-hp-pdq#section/all Saltz LB. J Support Oncol 2003;1:35-46. Saltz LB.J Support Oncol 2003;1:35-46.

CHANGES TO NORMAL GI FUNCTION GRADING

Bacterial Grade Description Lactose Malabsorption overgrowth in intolerance small bowel 1 Increase of <4 stools/day over baseline; mild increase in ostomy output compared with baseline 2 Increase of 4-6 stools/day over baseline; moderate increase in ostomy Reduced Bacterial Viral infection output compared with baseline transit time infection 3 Increase of 7 or more stools/day over baseline; incontinence; hospitalization indicated; severe increase in ostomy output; limiting self- Parasitic Pancreatic Hormone care activities of daily living infection chemotherapy secretion 4 Life-threatening consequences; urgent intervention indicated 5Death Changes in Stress neural signaling

Andreyev J, Ross P, Donnellan C et al. Lancet Oncol 2014;15;e447-60. National Cancer Institute. http://www.cancer.gov/about-cancer/treatment/side-effects/constipation/gi-complications-hp-pdq#section/all

CHEMOTHERAPY AND DIARRHEA CHEMOTHERAPY AND DIARRHEA

 Capecitabine  Interferon Regimen Percent with grade 3-4 diarrhea  Cisplatin  Irinotecan Irinotecan 6% Irinotecan + infused 15%  Cytarabine  Leucovorin Docetaxel 5%  Cyclophosphamide  Methotrexate Docetaxel + capecitabine 14%  Daunorubicin  Oxaliplatin Bolus fluoruracil 16%   Docetaxel Paclitaxel Infused fluorouracil 5%  Doxorubicin  Topotecan FOLFOXIRI 20%  5-fluorouracil  Lapatinib FOLFIRI 11-12% mIFL 19% capeIRI 47% FOLFIRI + cetuximab 16% FLOX 10% FLOX + cetuximab 17% National Cancer Institute. http://www.cancer.gov/about-cancer/treatment/side-effects/constipation/gi-complications-hp-pdq#section/all National Cancer Institute. http://www.cancer.gov/about-cancer/treatment/side-effects/constipation/gi-complications-hp-pdq#section/all Andreyev J, Ross P, Donnellan C et al. Lancet Oncol 2014;15;e447-60. Andreyev J, Ross P, Donnellan C et al. Lancet Oncol 2014;15;e447-60.

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MANAGEMENT: UNCOMPLICATED MANAGEMENT: COMPLICATED

Treat underlying cause (laxative use, etc.)

Dietary modification •Small, frequent meals •Avoid lactose, spicy foods, alcohol, caffeine, fruit juice, high-fiber foods, high-fat foods, cruciferous IV fluids and electrolyte supplementation vegetables which may be gas-producing •BRAT (bananas, rice, apples, toast) diet •Increase clear liquid intake to 3L/day (Gatorade, broth) Octreotide 100-150 mcg SubQ tid or 25-50 mcg/hr IV Loperamide •Binds to opioid receptors to increase transit time • Binds to somatostatin receptors, increases GI transit time, and •4mg then 2mg after each unformed stool decreases intestinal secretions •Effective in mild to moderate diarrhea • Efficacy demonstrated in fluoruracil-induced diarrhea Diphenoxylate- •Slows transit time •Effective in mild to moderate diarrhea Mucosal prostaglandin inhibitors •Bismuth subsalicylate • •Octreotide National Cancer Institute. http://www.cancer.gov/about-cancer/treatment/side-effects/constipation/gi-complications-hp-pdq#section/all National Cancer Institute. http://www.cancer.gov/about-cancer/treatment/side-effects/constipation/gi-complications-hp-pdq#section/all Saltz LB. J Support Oncol 2003;1:35-46. Saltz LB. J Support Oncol 2003;1:35-46.

Mechanism Indication Precautions Dose/administration Loperamide Opiate that 1st line for Risk of ileus if dosing 4mg PO followed by 2mg decreases diarrhea too aggressive every 2-4h or after every motility loose stool NCCN GUIDELINES: GRADE 1 Codeine Opioid, delays Alternative to Dose-limiting nausea, 15-60mg qid transit loperamide flatulence, sedation Octreotide Reduces Grade 1-2 high May reduce insulin 100mcg tid, increase if no  Oral hydration and electrolyte replacement secretions and risk; grade 3-4, requirements, may improvement in 24h up to  Loperamide 4mg PO once then 2mg PO after each loose stool motility or persistent precipitate steatorrhea 500mcg/day; SubQ or IV up to 16mg/day Budesonide Topical , 2nd line for Systemic effects 9mg PO daily for 3-5 days improves persistent possible, increased  Diphenoxylate/atropine 1-2 tabs PO q6h prn (max 8 tabs) mucosal uncomplicated risk of infection  Tincture of opium 10-15 drops PO q4h prn function diarrhea  BRAT diet Atropine Inhibition of Acute diarrhea Caution in elderly 0.25mg SubQ or IV acetylcholine <24h after patients,  Decrease dose or discontinue chemotherapy irinotecan contraindicated in glaucoma Bile acid Prevents water Diarrhea Interactions with PO Colestyramine 2-4g/day sequestrants secretion caused by medications with food or colesevelam induced by bile malabsorption up to 6x625mg tid with acids food Probiotics Unknown Prevention of Risk of infection in PO, dose varies diarrhea immunosuppression Palliative Care. NCCN Guidelines. Version 2.2015. Andreyev J, Ross P, Donnellan C et al. Lancet Oncol 2014;15;e447-60. Andreyev J, Ross P, Donnellan C et al. Lancet Oncol 2014;15;e447-60.

NCCN GUIDELINES: PERSISTENT GRADE 2 NCCN GUIDELINES: GRADE 2 – GRADE 4

 IV fluids if unable to tolerate oral  Inpatient admission  Initiate/continue antidiarrheal as in grade 1  Antidiarrheals as in grade 2  BRAT diet  IV fluids  Consider agents . 0.125mg PO/ODT/SL q4h prn (max 1.5mg/day)  Consider octreotide 100-500 mcg/day subQ or IV, q8h or . Atropine 0.5-1mg subQ, /IM/IV/SL q4-6h prn continuous infusion  If C. diff . Metronidazole 500mg PO/IV qid x 10-14 days . Vancomycin 125-500 mg PO qid x 10-14 days  Other antibiotics as appropriate if other infection  Delay or discontinue chemotherapy if cause  If ipilimumab-related . Corticosteroids 0.1-1 mg/kg/day . Infliximab 5mg/kg q2-6 weeks

Palliative Care. NCCN Guidelines. Version 2.2015. Palliative Care. NCCN Guidelines. Version 2.2015. Andreyev J, Ross P, Donnellan C et al. Lancet Oncol 2014;15;e447-60. Andreyev J, Ross P, Donnellan C et al. Lancet Oncol 2014;15;e447-60.

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INTRODUCTION

 Definitions . Anorexia – loss of desire to eat . – wasting, loss of muscle mass  Consequences of cachexia . Asthenia . Hypoalbuminemia ANOREXIA . Emaciation . impairment . Metabolic dysfunction . Autonomic failure

Palliative Care. NCCN Guidelines. Version 2.2015.

NCCN GUIDELINES: REVERSIBLE CAUSES

 Early satiety: treat with metoclopramide  Oral hygiene  Symptoms that interfere with intake  Saliva substitutes and oral moisturizers such as Biotene •  Gum or candy to stimulate residual salivary function • Xerostomia  Sialagogues • Oral-pharyngeal candidiasis . Pilocarpine • Mucositis • Nausea/vomiting • Dyspnea • Depression: treat with mirtazepine 7.5-30mg qhs • Constipation • Pain • : consider methylphenidate for patients undergoing active cancer treatment • Eating disorders/body image  Endocrine abnormalities Palliative Care. NCCN Guidelines. Version 2.2015. Radvansky LJ, Pace MB, Siddiqui A. Am J Health-Syst Pharm. 2013;70:1025-32.

NCCN GUIDELINES: APPETITE STIMULANTS

 Megestrol acetate 400-800 mg/day  Dexamethasone 2-8 mg/day

 Consider cannabinoid Outcome Relative Risk NNT Appetite improved 2.19 (95% Ci 1.41-3.4) 4  Consider an exercise program Weight improved 1.51 (95% CI 1.08-2.11) 12  Consider nutrition consult Deaths 1.42 (95% CI 1.04-1.94) 23  High-calorie Thromboembolic 1.84 (95% CI 1.07-3.18) 55  High-protein phenomena  Treat dry mouth with local measures

Palliative Care. NCCN Guidelines. Version 2.2015. Ruiz Garcia V, López-Briz E, Carbonell Sanchis R, Gonzalvez Perales JL, Bort-Marti S.. Cochrane Database of Systematic Reviews 2013, Issue 3. Art. No.: CD004310. DOI: 10.1002/14651858.CD004310.pub3.

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INTRODUCTION

 Definition . Mucosal damage secondary to cancer therapy . Occurring in the oral cavity; pharyngeal, laryngeal, and esophageal regions; and other areas of the GI tract  Incidence . 20-40% of patients receiving conventional chemotherapy MUCOSITIS . 80% of patients receiving high-dose chemotherapy as hematopoietic stem cell transplantation conditioning . Nearly all patients receiving radiation to the head and neck  Associated chemotherapy . Fluoropyrimidines (fluorouracil, capecitabine) . Anthracyclines . Methotrexate

Lalla RV, Bowen J, Barasch A et al.. Cancer 2014;120:1453-61. Sharma R, Tobin P, Clarke SJ. Lancet Oncol 2005;6:93-102.

INTRODUCTION PATHOPHYSIOLOGY

 Symptoms  Reactive oxygen species . Pain  Second messengers . Nausea  Proinflammatory cytokines . Vomiting . Diarrhea  Metabolic byproducts of colonizing microorganisms  Risk factors . Poor oral hygiene . Pre-existing mouth damage . Impaired immune status . High levels of pro-inflammatory cytokines

Lalla RV, Bowen J, Barasch A et al.. Cancer 2014;120:1453-61. Lalla RV, Bowen J, Barasch A et al.. Cancer 2014;120:1453-61. Sharma R, Tobin P, Clarke SJ. Lancet Oncol 2005;6:93-102. Sharma R, Tobin P, Clarke SJ. Lancet Oncol 2005;6:93-102.

PATHOPHYSIOLOGY MASCC/ISOO GUIDELINES

Irritation  GI mucositis . Recommend octreotide ≥100mcg twice daily to treat diarrhea if loperamide is ineffective

Upregulation Healing of messengers

Ulceration Signalling with and inflammation amplification

Lalla RV, Bowen J, Barasch A et al.. Cancer 2014;120:1453-61. Lalla RV, Bowen J, Barasch A et al.. Cancer 2014;120:1453-61. Sharma R, Tobin P, Clarke SJ. Lancet Oncol 2005;6:93-102.

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MASCC/ISOO GUIDELINES ORAL MUCOSITIS MANAGEMENT

 Oral mucositis  Oral mucositis . Recommend 30 minutes of oral cryotherapy to prevent mucositis in . Suggest oral care for prevention of mucositis patients receiving bolus 5-fluorouracil . Tooth brushing, flossing, mouth rinses . Recommend to prevent oral mucositis in patients . Purpose is to reduce microbial flora, prevent infection, and receiving high-dose chemotherapy and total body irradiation followed reduce pain by autologous stem cell transplantation . Avoid spicy, acidic, irritating foods . Palifermin is a recombinant keratinocyte growth factor . Inadequate evidence for for guidelines . Can worsen mucositis if given within 24h before or during . Mouth rinses may contain a topical (lidocaine), chemotherapy , and a coating agent (Maalox) . Recommend low-level laser therapy to prevent oral mucositis in . Mouth rinses provide short-term relief and systemic therapy may patients receiving HSCT be required . Recommend PCA with morphine to treat pain due to oral mucositis

Lalla RV, Bowen J, Barasch A et al.. Cancer 2014;120:1453-61. Lalla RV, Bowen J, Barasch A et al.. Cancer 2014;120:1453-61. Radvansky LJ, Pace MB, Siddiqui A. Am J Health-Syst Pharm. 2013;70:1025-32. Lalla R, Saunders DP, Peterson DE. Dent Clin North Am. 2014;58(2):341-9.

CONCLUSIONS REFERENCES

 Nausea, vomiting, diarrhea, constipation, anorexia, and mucositis are  National Comprehensive Cancer Network. Antiemesis. NCCN Guidelines Version1.2015.  National Comprehensive Cancer Network. Palliative Care. NCCN Guidelines Version2.2015. commonly encountered gastrointestinal toxicities of chemotherapy  American Society of Clinical Oncology 2011. www.asco.org/guidelines/antiemetics.  National Cancer Institute. Gastrointestinal Complications – for health professionals. Available at http://www.cancer.gov/about-cancer/treatment/side-effects/constipation/gi-complications-hp-  Medications should be administered to prevent chemotherapy-induced pdq#section/all. Accessed 1 June 2015.  Saltz LB. Understanding and Managing Chemotherapy-Induced Diarrhea. J Support Oncol 2003;1:35- nausea and vomiting according to risk category 46.  Andreyev J, Ross P, Donnellan C et al. Guidance on the management of diarrhoea during cancer chemotherapy. Lancet Oncol 2014;15;e447-60  Diarrhea can usually be managed with loperamide, but consideration of  Lalla RV, Bowen J, Barasch A et al. MASCC/ISOO Clinical Practice Guidelines for the Management of Mucositis Secondary to Cancer Therapy. Cancer 2014;120:1453-61 other causes such as infection is important  Gibson RJ, Keefe DMK. Cancer chemotherapy-induced diarrhea and constipation: mechanisms of damage and prevention strategies. Support Care Cancer 2006;14:890-900.  Shailender B, Huber B, Upton MP et al. Inflammatory enteric neuropathy with severe constipation after ipilimumab treatment for melanoma: a case report. J Immunother. 2009;32:203-5.  Many OTC agents are available for treatment and prevention of  PashankarP, Season JH, McNamara J et al. Acute constipation in children receiving chemotherapy for constipation cancer. J Pediatr Hematol Oncol 2011;33:e300-3.  Harriis AC, Jackson JM. Lactulose in vincristine-induced constipation. Med J Aust. 1977;2:573-4.  Sharma R, Tobin P, Clarke SJ. Management of chemotherapy-induced nausea, vomiting, oral mucositis, and diarrhoea. Lancet Oncol 2005;6:93-102.  Appetite stimulants such as megestrol may be used in cancer patients  Ruiz Garcia V, López-Briz E, Carbonell Sanchis R, Gonzalvez Perales JL, Bort-Marti S. Megestrol but are limited by adverse effects acetate for treatment of anorexia-cachexia syndrome. Cochrane Database of Systematic Reviews 2013, Issue 3. Art. No.: CD004310. DOI: 10.1002/14651858.CD004310.pub3.  Radvansky LJ, Pace MB, Siddiqui A. Prevetional and management of radiation-induced dermatitis, mucositis, and xerostomia. Am J Health-Syst Pharm. 2013;70:1025-32.’  Management of mucositis includes oral care, treatment of pain, and  Lalla R, Saunders DP, Peterson DE. Chemotherapy or radiation-induced oral mucositis. Dent Clin other prevention strategies for certain populations North Am. 2014;58(2):341-9

CHEMOTHERAPY TOXICITY AND SUPPORTIVE CARE: MANAGEMENT OF GASTROINTESTINAL SYMPTOMS

Leah Edenfield, PharmD, BCPS PGY2 Oncology Pharmacy Resident

June 12, 2015

10