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Management of Chemotherapy Complications

Management of Chemotherapy Complications. Elshami M. Elamin , MD Medical Oncologist Central Care Cancer Center www.cccancer.com Wichita, KS - USA. Introduction. Chemotherapy: A ffects the rapidly dividing cancer cells Also affects rapidly dividing normal cells Hair

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Management of Chemotherapy Complications

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  1. Management of Chemotherapy Complications Elshami M. Elamin, MD Medical Oncologist Central Care Cancer Center www.cccancer.com Wichita, KS - USA

  2. Introduction • Chemotherapy: • Affects the rapidly dividing cancer cells • Also affects rapidly dividing normal cells • Hair • Mucous membranes • Blood cells

  3. Effect of chemo on blood counts Because stem cells in BM do not reproduce rapidly they are less likely to be affects During hematopoiesis (differentiation) the blood cells are sensitive to chemo and most likely to be damaged After the mature cells (neutrophils, platelets) live out their life span, the blood count fall to THENADIR

  4. What is the chemo nadir? • Lowest blood counts following chemo • The nadir time is usually about 10 days (7-14 days) after chemo • It varies depending on the drugs • Risk of infection and bleeding • The next dose of chemotherapy is given only after: • The nadir • BM recovers (3-4 wks)

  5. Why chemo given in Cycles (q3-4 wks?) • The nadir (7-14 days) • BM recovery (3-4 wks) • What if chemotherapy is given during BM recovering period (increasing stem cell production)? • It may cause: • Prolonged myelosuppression • Permanent BM damage

  6. 10.0 New cycle 8.0 Regimen C 6.0 W.B.C. Regimen A 4.0 Regimen B 2.0 Day 0 (Chemo Starts) Day 7 Day 21 Nadir

  7. Chemotherapy Side Effects • Immediate • Delayed • within days • Within weeks • Late

  8. Immediate Side Effects • Allergic reactions: • Infusion-related • Rituximab • Anaphylactic • Burning sensation or pain at the site of infusion • Irritant • Vesicant • Urine discoloration • Doxorubicin  Red • Mitoxantrone  Blue

  9. Immediate Side Effects • Acute emesis (Nausea/Vomiting): • Within few min – Hrs • Peaks after 5-6 hrs • Resolves within first 24 hrs • Related to: • Age • Gender • Place • History of alcoholism (reduce it) • History of motion sickness • Chemo drugs • Anti-emetic used

  10. Within days • Delayed-onset emesis: • > 24 hrs after chemo – 7 days • Related to types of chemo drugs (Platinum, Cytoxan, Doxo) • Fatigue • Myelosuppression: • During the nadir of chemo • Mucositis • Neuropenic fever +/- infection • Diarrhea or Constipation • Reduced appetite • Metallic taste

  11. Within weeks • Hair loss (Alopecia) • Taxanes, Cisplatin, Doxo • Peripheral neuropathy • Pacltaxel, Oxalipatin, Cisplatin • Dry skin or pigmentaion • Nail changes • Fluid retention • Docetaxel

  12. Late Side effects • Ototoxicity • Cisplatin • Memory difficulties (chemo brain) • Sexual dysfunction • Amenorrhea • Sterility • MDS, leukemia • Alkyl agent (2-5yrs), cytoxan(MDS 8-10 yrs) • Topoisoll inhibitor: usually M4, M5ALL (1-2 yrs) • 11q23, 21q22, inv 16, t(15:17), t(9:22), t(4:11), t(3:21), t(16:21), t(8:16) • Mitoxantrone(2-3 yrs) • Cardiotoxicity • Anthracyclines • Pulmonary fibrosis • Bleomycin

  13. Resolved ?

  14. Management of a cancer patient who is undergoing chemotherapy

  15. What is the patient status? • SOAP: • Subjective: • Fever, pain, S.O.B., cough, bleeding, diarrhea etc … • Objective: • A/O x 3 • V.S.: BP, Pulse, Temp, RR, O2 • Dehydration • Mucositis • Does the pt has a venous catheter • Routine full system exam • Assessment: • Plan:

  16. TREATMENT OF SIDE EFFECTS AND COMPLICATIONS OF CANCER THERAPIES

  17. What do you need to know? • When was the chemotherapy given? • Are you dealing with chemo NADIR • Any supportive therapy following the chemo was given? • List of medication • What kind of cancer? • What kind of chemotherapy /regimen?

  18. EMESIS(Nausea/Vomiting)

  19. Causes of N/V in cancer patients • Chemo • RT • Bowel obstruction • Brain mets • Electrolytes imbalance • Hypercalcemia, • Hyponatremia, • Hyperglycemia • Uremia • Opiates • Gastroparesis (Vincrestine) • Psycophysiologic: • Anxiety • Anticipating N/V

  20. CINV It is easier to prevent N/V than to treat it Always remember Dyspepsia may mimic nausea • Acute • Onset: minutes-hrs • Resolves: first 24 hrs • Delayed • Platinum, Cytoxan, Doxo • Onset: >24 hrs • May last for 7 days • Anticipatory • Breakthrough/Refractory

  21. Which anti-emetic you should chose for your patient? • Anti-emetic regimens should be chosen based on: • Chemo drugs and their sequence in the regimen • Acute and delayed emesis may overlap • Goal of chemo: Palliative vsAdj/curative • Patient specific risk factors • Smoker • Alcoholic: less N/V • Gender, Age (more CINV in young female) • Hx of N/V or motion sickness • Prior experience with anti-emetics

  22. Categories of Emetogenic Chemotherapy *Don’t undertreat *Don’t underestimate High emetic risk Moderate emetic risk Low emetic risk Minimal emetic risk

  23. Lorazepam 5-HT3 Antagoist Aprepitant Dexa PPI/H2-blocker Dopamine antagonist

  24. Management of Delayed Emesis

  25. Dopamine antagonists Metoclopramide (Reglan) and Domperidone (Motilium) Sensitize tissues to acetylcholine Stimulate upper GIT motility Facilitate gastric emptying Increase esophageal peristalsis Increase LES pressure Antagonize central and peripheral dopamine receptors Block dopamine receptors in chemoreceptor trigger zone in CNS 2- Haloperidol

  26. Anxiolytics/Anti-psychotics Benzodiazepine (Lorazepam) May give the night before and after chemo Phenothiazine: Prochlorperazine (Compazine): Anti-dopaminergic effect Blocking dopamine receptors Blocking vagus nerve in GIT

  27. Watch for Dystonic reaction 1- Diphenhydramine OR 2- Benztropine (Cogentin) Prochlorperazine Metoclopramide Domperidone

  28. Steroids *Acute emesis: PO/IV Prior to mod-highly emetogenic chemo *Delayed emesis: Days 2-3 • Dexamethasone • Improve efficacy of 5-HT3 antagonists • With Aloxi for moderate risk: • 8 mg d1 enough • No need on d 2-3 • Do Not use if chemo include steroids • e.g. ESHAP • Contra-indicated with: • IL-2 • IFN

  29. Steroids *Hyerglycemia *HTN *Fluid retension *PU *Osteoporosis • Dexamethasone • Always keep in mind its side effects

  30. Serotonin (5-HT3) Antagonists • 5-HT3 antagonists (except aloxi/palonosetron) are less effective for delayed emesis • A meta-analysis of randomized controlled trials: • Adding 5-HT3 antagonist to Dexa did NOT improve antiemetic effect of Dexa for delayed emesis • Another study: • 5-HT3 antagonists (except Aloxi, not studied) NOT more effective than prochlorperazine for delayed emesis • A Canadian meta-analysis: • Ondansteron alone did help for delayed emesis • Not cost-effective to use 5-HT3 antagonists on d 2-4

  31. Miscellaneous • Antipsychotic : • Olanzapine (zyprexa) • Cannabinol: • Dronabinol (marinol) 5-10 mg OR Nabilone 1-2 mg • Anti-histamine: • Promethazine (phenergan) • H2-Blocher or PPI

  32. MANAGEMENT OF BREAKTHROUGH (REFRACTORY)EMESIS

  33. Breakthrough CINV • The most difficult to treat • Consider routine (around the clock) rather than PRN • Rectal or IV rather than PO • Multiple, alternating agents and perhaps routes • Do not forget: • Hydration • Electrolytes • Brain mets • GI tumors

  34. Breakthrough Treatment for CIN/V First Step: • Add one agent from a different drug class PRN • Antipsychotic : • Olanzapine (zyprexa) 2.5-5 mg po bid • Caution: elderly, DM • Benzodiazepine: • Lorazepam 0.5-2 mg • Cannabinol: • Dronabinol 5-10 mg OR Nabilone 1-2 mg • Dopamine antagonists: • Metoclopromide , Domperidone, Haloperidol • Phenothiazine: Prochlorperazine OR Promethazine • Serotonin 5-HT3 antagonists • Dexa

  35. Breakthrough Treatment for CIN/V Second Step: Continue agent on Schedule Not PRN N/V controlled Agents from different drug class PRN Consider change antiemetics to higher level for next cycle N/V Not controlled Re-eval, adjust dose and or new drug

  36. Anticipatory N/V • Negative bad experience with chemo • 18-57% of patients • N > V • Prevention: • Optimal anti-emetic with each cycle • Acupuncture • Alprazolam 0.5-2 mg potid beginning night before Or • Lorazepam 0.5-2 mg po night before and am

  37. It is not always medication to do it … It is not always doctors and nurses to do it … It is most of the time the patient to do it … It could be simple and easy ….

  38. Eating small frequent meals Choice of food Easy on stomach Eating food at room temperature Non-Medical measures Dietary consult

  39. Behavioral therapy • Relaxation/systematic desensitization • Hypnosis with guided imagery • Music therapy • Spiritual

  40. Radiation-Induced N/V • R.T. - upper abdomin: • Pretreatment daily: • Granisetron 2 mg qd OR • Ondansetron 8 mg bid • +/- Dexa 4 mg qd • TBI: • Pretreatment: • Granisetron 2 mg qd OR • Ondansetron 8 mg bid-tid • +/- Dexa 4 mg qd • ChemoRT: • CIN/V protocol

  41. CANCER-RELATED INFECTIONS TREATMENT PREVENTION

  42. PREVENTION Neutropenic precaution Prophylactic antimicrobials G-CSF

  43. Neutropenic precaution • Hand wash • Gloves, Gowns, etc • Accessing central venous lines: • Written policy • Training of medical staff • Isolation

  44. Prophylactic antimicrobials

  45. RISK CATOGERIES

  46. Fungal prophylaxis • Pts with hematologic malignancies and SCT not on antifungal prophylaxis: • Severe mucositis is a risk factor for candidemia • Consider for all GVHD patients on immunosuppressants • Acute leukemia receiving induction or re-induction • When selecting drugs: • Take into account local susceptibility pattern • Remember: Itraconazole, voriconazole, posaconazole are potent inhibitors of cytochrome P450 3A4 isoenzymes than floconazole • May decrease clearance of some chemo drugs • A lipid formulation is preferred based on less toxicity

  47. Anti-viral Prophylaxis • For low risk pts: • None • Prior HSV: during neutropenia • Intermediate risk pts: • During neutropenia + 30 days after SCT • High risk: • Acute leukemia: • During neutropenia • Alemtuzumab: • During and minimum 2 m after Alemtuzumab and until CD4 > 200 • ASCT: During neutropenia + 30 days after SCT • Allo SCT: for the first yr

  48. CMV Prevention • High risk groups and surveillance period : • 1-6 m after SCT • GVHD • Minimum of 2 m after Alemtuzumzb • Surveillance done wkly by PCR or Ag testing • Pre-emptive therapy: • Ganciclovir, Foscarnet, Valganciclovir (PO) • At least 2 wks and until CMV not detected

  49. PCP Prophylaxis(PneumocystisJirovecii) Considered Fludara, T-cell depleting agents Until CD4 > 200 Prolonged steroids (e.g. Pred> 20mg qd x > 4 wks0 Temodar + RT ASCT For 3-6 m after it Recommended • Allo SC • For 6 m and while on immunosuppressants • ALL • Throughout anti-leukemic • Alemtuzumab • For minimum of 2 m after it

  50. PCP Prophylaxis(PneumocystisJirovecii) • Drugs of choice: • TMP/SMX • Preferred • If allergic or intolerant: • Desensitization or • Dapsone, aerosolized Pentamidine, Atovaquone

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