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How to manage adverse events from oncologic treatments.pdf
- 1. HOW TO MANAGE ADVERSE EVENTS FROM ONCOLOGIC TREATMENTS A Guide for Internists Lance Catedral, MD, MCMMO, FPCP lance.catedral@msugensan.edu.ph @lanceoncology
- 2. CANCER TREATMENT- RELATED ADVERSE EVENTS Hypersensitivity 01 02 Extravasation reactions 03 Nausea/vomiting 04 Diarrhea Mucositis 05 06 Fatigue 07 Peripheral neurotoxicity 08 Cutaneous manifestations
- 3. Internists are in a great position to care for cancer treatment side effects
- 6. CANCER TREATMENT- RELATED ADVERSE EVENTS Hypersensitivity 01 02 Extravasation reactions 03 Nausea/vomiting 04 Diarrhea Mucositis 05 06 Fatigue 07 Peripheral neurotoxicity 08 Cutaneous manifestations
- 7. HYPERSENSITIVITY REACTIONS generally infrequent occur more commonly with L-asparaginase paclitaxel docetaxel teniposide procarbazine, and cytarabine Allergic reactions
- 8. DETECT EARLY SIGNS → STOP THE INFUSION AND ASSESS THE PATIENT Light-headedness / ‘feeling strange’, unwell or nauseous Rashes particularly urticarial in nature Facial flushing Loin pain / abdominal cramping Bronchospasm / breathlessness/swelling or tightness in mouth or throat Rapid or involuntary emptying of bowel and / or bladder Pallor, low blood pressure, low oxygenation Throat & tongue swelling / hoarse voice Slide adapted from the slide set of Dr. Mike San Juan, UP PGH
- 9. MILD TO MODERATE HYPERSENSITIVITY REACTION Administer Dipenhydramine 25 mg IV Hydrocortisone 100-200 mg IV Monitor vital signs closely Stop the infusion Slide adapted from the slide set of Dr. Mike San Juan, UP PGH
- 10. STOP the infusion but maintain IV access. Call for help. Notify nurses/emergency team. Oxygen support, standby intubation Epinephrine Severe reactions: stridor, major bronchospasm, severe hypotension à 0.3-0.5mg (0.3-0.5mL 1:1000 epinephrine or 3-5mL 1:10,000 solution) IV is given every 10minutes Milder reactions: 0.2-0.3mL of 1:1,000 SC repeated q15minutes 2 Life threatening: 0.5mg (5mL 1:10,000 solution) IV repeated once after 10 minutes IV fluids (pLR or pNSS) for hypotension Albuterol or salbutamol nebulization for bronchospasm Diphenhydramine 25mg IV Hydrocortisone (not for acute mgt, response is delayed): 100-500mg IV or methylprednisolone 125mg IV Cimetidine 300mg IV or other H2 blockers for urticaria SEVERE HYPERSENSITIVITY REACTION Slide adapted from the slide set of Dr. Mike San Juan, UP PGH
- 11. CANCER TREATMENT- RELATED ADVERSE EVENTS Hypersensitivity 01 02 Extravasation reactions 03 Nausea/vomiting 04 Diarrhea Mucositis 05 06 Fatigue 07 Peripheral neurotoxicity 08 Cutaneous manifestations
- 12. IRRITANT inflammatory reactions generally not tissue necrosis Bendamustine Carmustine Cisplatin Dacarbazine Fluorouracil Topotecan VESICANT causes tissue necrosis Dactinomycin Daunorubicin Doxorubicin Docetaxel* Epirubicin Mitomycin Vinblastine Vincristine Vinorelbine
- 13. SUSPECT EXTRAVASATION Swelling Stinging Burning discomfort Erythema or blanching = Poor flow in IV site Image: Onesti et al. (Ann Plast Surg 2017;00: 00–00
- 14. Image credit: D.M. Boyle and C. Engelking, 1995, Oncology Nursing Forum, 22, p. 60. Copyright 1995 by the Oncology Nursing Society. Image credit: https://www.slideserve.com/brooke/extravasation
- 15. vinca alkaloids and etoposide: apply heat other vesicant agents: apply cold topically anthracyclines: dexrazoxane (not locally available) vinca alkaloids and taxanes: local injection of hyaluronidase Specific therapies: Stop drug administration Elevated affected extremity Do not remove catheter or needle immediately Aspirate fluid from extravasated area Administration of antidotes to the local area If no antidote to be given, aspirate fluid then remove needle IF EXTRAVASATION IS SUSPECTED
- 16. CANCER TREATMENT- RELATED ADVERSE EVENTS Hypersensitivity 01 02 Extravasation reactions 03 Nausea/vomiting 04 Diarrhea Mucositis 05 06 Fatigue 07 Peripheral neurotoxicity 08 Cutaneous manifestations
- 17. NAUSEA/VOMITING Chemotherapy induced nausea and vomiting Types: acute (within 24 h of chemotherapy) delayed (>24 h) anticipatory of the receipt of chemotherapy NCCN Guideline on Antiemesis Version 1.2022
- 18. EMETIC RISK Very high (>90%) Cisplatin Dacarbazine Melphalan Dactinomycin Lomustine Streptozocin Pentostatin Meclorethamine High (60%-80%) Cyclophosphamide Etoposide Methotrexate Procarbazine Carmustine Cytarabine Busulfan Irinotecan Moderate (30%-60%) Carboplatin* 5-FU Idarubicin Ifosfamide Doxorubicin Vinorelbine Epirubicin Mitomycin-c Low (10% -30%) Gemcitabine Vinblastine Topotecan Docetaxel Daunorubicin Capecitabine Chlorambucil Teniposide Low (<10%) Fludarabine Hydroxyurea Vincristine Vinblastine Paclitaxel, Docetaxel Pemetrexed Oxaliplatin Biologics NCCN Guideline on Antiemesis Version 1.2022
- 19. Olanzapine 5-10 mg PO Aprepitant 125 mg PO Ondansetron 8 mg IV Dexamethasone 12 mg IV Olanzapine 5-10 mg PO daily on days 2, 3, 4 Aprepitant 80 mg PO daily on days 2, 3 Dexamethasone 8 mg PO/IV on days 2,3, 4 Example: Before chemotherapy: After chemotherapy: type 3 5-hydroxytryptamine (5-HT3) receptor antagonists neurokinin-1 receptor (NK1R) antagonists glucocorticoids olanzapine ACUTE AND DELAYED NAUSEA AND VOMITING NCCN Guideline on Antiemesis Version 1.2022
- 20. Behavioral therapy relaxation/systematic desensitization hypnosis relaxation exercises cognitive distraction yoga Acupuncture/acupressure Anxiolytic therapy (e.g., lorazepam on the night before treatment) Treatment options prevention is key optimal antiemetic therapy avoid strong smells ANTICIPATORY NAUSEA/VOMITING NCCN Guideline on Antiemesis Version 1.2022
- 21. MANAGING POORLY CONTROLLED CINV Exclude disease- and medication-related causes of emesis Ask about compliance to antiemetic regimen General principle: add one agent from a different class to the current regimen Atypical antipyschotic (Olanzapine 5- 10 mg PO daily) Metoclopramide PO/IV every 4-6 h Benzodiazepine (e.g., lorazepam) Cannabinoid (e.g., dronabinol capsules) Haloperidol Phenothiazine (e.g., prochlorperazine) 5-HT3A (e.g., ondansetron, dolasetron) Corticosteroid (e.g., dexamethasone) NCCN Guideline on Antiemesis Version 1.2022
- 22. CANCER TREATMENT- RELATED ADVERSE EVENTS Hypersensitivity 01 02 Extravasation reactions 03 Nausea/vomiting 04 Diarrhea Mucositis 05 06 Fatigue 07 Peripheral neurotoxicity 08 Cutaneous manifestations
- 23. DIARRHEA Chemotherapy-induced diarrhea Common problem Notorious: fluoropyrimidines (5FU and capecitabine) irinotecan molecularly targeted agents immune checkpoint inhibitor
- 24. Assess stools: number and composition Check for signs of complicated diarrhea Manage accordingly WHAT TO DO
- 25. Grade 1 Grade 2 Grade 3 Grade 4 Grade 5 Increase of <4 stools per day over baseline; mild increase in ostomy output compared with baseline Increase of four to six stools per day over baseline; moderate increase in ostomy output compared with baseline; limiting instrumental ADL Increase of seven or more stools per day over baseline; hospitalization indicated; severe increase in ostomy output compared with baseline; limiting self-care ADL Life-threatening consequences; urgent intervention indicated Death LOPERAMIDE; IF PERSISTENT DIARRHEA: OCTREOTIDE HOSPITAL ADMISSION
- 26. abdominal cramping nausea/vomiting grade 2 or worse deteriorating performance status fever possible sepsis neutropenia gross bloody stools dehydration chest pain prior admission for chemotherapy-related diarrhea COMPLICATED DIARRHEA
- 27. GRADE 1-2 DIARRHEA Uncomplicated 1 Discontinue chemotherapy 2 Stop lactose-containing products Drink 8-10 glasses of clear liquids 4 Reassess 12 to 24 hours later 5 If grade 1 or 2 diarrhea is persistent: increase loperamide to 2 mg every 2 hours 3 Oral loperamide (initial dose 4 mg → every 4 hours after each unformed stool Reassess
- 28. GRADE 1-2 DIARRHEA After reassessment If grade 1 or 2 diarrhea is persistent: stool work up for infectious cause CBC and electrolytes Add second-line: octreotide 100 to 150 mcg three times daily subcutaneously If diarrhea is resolving: add solid food discontinue oral loperamide after 12 h diarrhea-free interval Assess need for chemotherapy dose reduction
- 29. Admit to hospital Stool work up for infectious causes CBC and electrolytes, blood cultures CT scan Discontinue chemotherapy until resolution IV fluids and antibiotics, as needed Loperamide (oral) 2 mg initially, then 2 mg every 2 hours or 4 mg every 4 hours until diarrhea free for 12 hours Octreotide 100-150 mcg SC thrice a day If not improved with loperamide and octreoide: refer to GI for upper endoscopy and sigmoidoscpy GRADE 3 TO 4 DIARRHEA (SEVERE) GRADE 1 OR 2 DIARRHEA WITH RISK FACTOR FOR COMPLICATED DIARRHEA
- 30. CANCER TREATMENT- RELATED ADVERSE EVENTS Hypersensitivity 01 02 Extravasation reactions 03 Nausea/vomiting 04 Diarrhea Mucositis 05 06 Fatigue 07 Peripheral neurotoxicity 08 Cutaneous manifestations
- 31. MUCOSITIS Image created by Sook-Bin Woo, MS, DMD, MMSc. Chemotherapy bleomycin cytarabine doxorubicin high-dose etoposide bolus fluorouracil (FU) regimens methotrexate Molecularly targeted agents agents that block signaling through the epidermal growth factor receptor and the fibroblast growth factor receptor mechanistic (previously called mammalian) target of rapamycin (mTOR) inhibitors The principal manifestation of oral toxicity
- 32. Grade 1 Grade 2 Grade 3 Grade 4 Grade 5 Asymptomatic or mild symptoms Moderate pain or ulcer that does not interfere with oral intake Severe pain, interfering with oral intake Life-threatening consequences; urgent intervention indicated Death
- 33. Comprehensive oral examination before treatment FU-containing cytotoxic chemotherapy: oral cryotherapy (ice chips swished around the mouth for 30 minutes) PREVENTION Prophylactic oral care
- 34. Limit diet to foods that do not require significant chewing; avoid acidic, salty, or dry foods. Patients unable to swallow foods or liquids, may require parenteral fluid and/or nutritional support. Adequate analgesia Other complaints: Xerostomia Therapy is symptomatic (eg, rinsing with saline or the use of commercially available saliva substitutes). Dry, cracked lips can be treated with petroleum lubricants. For all patients, removal of dentures, atraumatic cleansing, and oral rinses with a weak solution of salt and baking soda (one-half teaspoon of salt and one teaspoon of baking soda in a quart of water) every four hours The oral cavity should be rinsed and wiped after meals, and dentures cleaned and brushed often to remove plaque. TREATMENT
- 35. CANCER TREATMENT- RELATED ADVERSE EVENTS Hypersensitivity 01 02 Extravasation reactions 03 Nausea/vomiting 04 Diarrhea Mucositis 05 06 Fatigue 07 Peripheral neurotoxicity 08 Cutaneous manifestations
- 36. distressing, persistent, subjective sense of physical, emotional, and/or cognitive tiredness or exhaustion related to cancer or cancer treatment that it not proportional to recent activity and interferes with usual functioning Cancer-related fatigue THERAPY-RELATED FATIGUE
- 37. Evaluate for and correct anemia PATIENTS RECEIVING ACTIVE CANCER THERAPY ESAs RBC transfusion Risks thrombotic events potentially decreased survival transfusion reactions circulatory overload iron overload Benefits gradual improvement in hemoglobin/hct gradual clinical improvement rapid improvement in hemoglobin/hct rapid clinical improvement
- 38. ESAS must be due to treatment for a nonhematologic malignancy other treatable causes of anemia (eg, blood loss, hemolysis, nutritional deficiency [eg, iron, B12, folate]) should be excluded or treated if present initial hemoglobin level of 10 g/dL or less Contraindications to use of an ESA: predisposition to thromboembolism (eg, prior history of thromboses, surgery, prolonged periods of immobilization or limited activity, multiple myeloma treated with an immunomodulatory agent plus an anthracycline or high-dose corticosteroid) uncontrolled hypertension
- 39. Cognitive behavioral intervention structured groups individual counseling for stress management, depression and anxiety stress management relaxation training mind-body therapies / mindfulness-based approaches (e.g., yoga) individualized program of moderate aerobic exercise unless contraindicated WITHOUT ANEMIA
- 40. MODERATE TO SEVERE FATIGUE Therapeutic trial therapeutic trial of a psychostimulant or other wakefulness agent (methylphenidate, dexmethylphenidate, or modafinil) Others: complementary medicine approaches American or Korean ginseng is reasonable → do not give if on anticoagulants Multivitamins -- evidence is inconclusive (Support Care Cancer. 2010 Feb;18(2):179-87. Epub 2009 May 6; Eur J Cancer. 2020;130:51. Epub 2020 Mar 13. )
- 41. CANCER TREATMENT- RELATED ADVERSE EVENTS Hypersensitivity 01 02 Extravasation reactions 03 Nausea/vomiting 04 Diarrhea Mucositis 05 06 Fatigue 07 Peripheral neurotoxicity 08 Cutaneous manifestations
- 42. CHEMOTHERAPY-INDUCED PERIPHERAL NEUROTOXICITY dose-dependent and cumulative asymmetrical, distal, "stocking and glove" distribution predominantly sensory more than motor symptoms
- 43. Agent Pattern Resolution Cisplatin Distal, symmetric loss of sensation to all modalities, stocking glove distribution; painful paresthesias or numbness Partial; may progress for several months after drug is discontinued Oxaliplatin Acute: Cold-induced dysesthesias in mouth, throat, and upper limbs Chronic: similar to cisplatin Generally starts to improve approximately three months after completion of chemotherapy Vinca alkaloids (vincristine, vinblastine, vinorelbine, vindesine) Distal sensory loss lower extremities, rarely affects upper extremities Usually resolves within three months; may persist with vincristine Taxanes (paclitaxel, docetaxel) Mild distal loss of sensation to all modalities, feet greater than hands, painful paresthesias Usually improves after treatment, but persistent symptoms in about 50% of patients one year later
- 44. PREVENTION No established prevention TREATMENT CIPN from taxanes and platinum drugs: duloxetine Insufficient evidence to support gabapentin/pregabalin Possible benefit: scrambler therapy (electro-analgesia therapy) acupuncture exercise
- 45. CANCER TREATMENT- RELATED ADVERSE EVENTS Hypersensitivity 01 02 Extravasation reactions 03 Nausea/vomiting 04 Diarrhea Mucositis 05 06 Fatigue 07 Peripheral neurotoxicity 08 Cutaneous manifestations
- 46. Payne AS, James WD, Weiss RB. Dermatologic toxicity of chemotherapeutic agents. Semin Oncol 2006; 33:86. HAND FOOT SYNDROME Acral erythema notable in cytarabine, capecitabine and 5FU tinging sensation of palms and soles painful pathogenesis: unknown
- 47. TREATMENT topical corticosteroids to decrease inflammation wound care for erosions and ulcerations to prevent infection emollients and topical keratolytics to decrease hyperkeratosis analgesics for pain control
- 48. Payne AS, James WD, Weiss RB. Dermatologic toxicity of chemotherapeutic agents. Semin Oncol 2006; 33:86. HAND-FOOT SKIN REACTION FROM TYROSINE KINASE INHIBITOR Appears in the first 2-4 weeks of TKIs bullae and blisters in areas of friction or pressure in palms and soles (vs. chemo HFS which presents with a diffuse erythema and scale involving entire palm and sole) painful
- 49. GRADE 1 GRADE 2 GRADE 3 Minimal skin changes or dermatitis (eg, erythema, edema, or hyperkeratosis) without pain Skin changes (eg, peeling, blisters, bleeding, edema, or hyperkeratosis) with pain, limiting instrumental ADL* Severe skin changes (eg, peeling, blisters, bleeding, edema, or hyperkeratosis) with pain, limiting self-care ADL* Continue TKI at current dose and monitor for change in severity Keratolytic emollients containing topical urea 10% 3 times per day topical analgesics Add: topical corticosteroid oral analgesics Hold TKI for 7 days until symptoms resolve Common Terminology Criteria for Adverse Events (CTCAE), Version 5.0, November 2017, National Institutes of Health, National Cancer Institute. Available at: https://ctep.cancer.gov/protocoldevelopment/electronic_applications/docs/CTCAE_v5_Quick_Reference_8.5x11.pdf (Accessed March 27, 2018).
- 50. Payne AS, James WD, Weiss RB. Dermatologic toxicity of chemotherapeutic agents. Semin Oncol 2006; 33:86. MULTIDISCIPLINARY APPROACH TO CARE oncologist, dermatologist, podiatrist, and nursing care