Oncology Supportive Care PDF

Oncology Supportive Care Noha Osama Mansour, PhD Supportive Care in Oncology 2 Myelosuppression NEUTROPENIA ANEMIA THROMBOCYTOPENIA Supportive Care in Oncology 3 I. Myelosuppression...

Oncology Supportive Care Noha Osama Mansour, PhD Supportive Care in Oncology 2 Myelosuppression NEUTROPENIA ANEMIA THROMBOCYTOPENIA Supportive Care in Oncology 3 I. Myelosuppression 1. Neutropenia I. Myelosuppression 4 Bone marrow suppression is the most common dose-limiting toxicity associated with traditional cytotoxic chemotherapy. Myelosuppression (decrease in bone marrow activity, resulting in fewer RBCs, WBCs and platelets} is a complication of most chemotherapy regimens. Myelosuppression The lowest point that WBCs and platelets reach is called the nadir, which occurs {with most drugs} about 7 - 14 days after chemotherapy. The RBC nadir is much later, generally after several months of treatment, due to the long-life span of RBCs (-120 days). I. Myelosuppression 5 Myelosuppression Recovery WBCs and platelets generally recover 3 - 4 weeks post treatment. The next dose of chemotherapy is given after the WBCs and platelets have returned to a safe level (To receive chemotherapy, in general, a patient should have a WBC greater than 3000 cells/mm3 or an ANC greater than 1000 cells/mm3 and a platelet count of 100,000 cells/mm3 or more). The next cycle of chemotherapy may need to be delayed to give more time for recovery. Drugs that hasten recovery can be needed. Severe cases can require a transfusion (e.g., giving packed RBCs for severe anemia). 6 7 Neutropenia 8 Neutropenia, a type of leukopenia, is a low neutrophil count that is assessed by calculating an absolute neutrophil count {ANC). The more significant the neutropenia (i.e., the lower the ANC), the higher the risk of infection. ANC = WBC × percentage granulocytes or neutrophils (segmented neutrophils plus band neutrophils). Example: A patient’s WBC = 4500 cells/mm3 with 10% segmented neutrophils and 5% band neutrophils. What is the ANC? 4500 × (0.1 + 0.05) = 675 cells/m3. Neutropenia 9 Neutropenia is defined as an ANC of ≤500 cells/mm3 or a count of ≤1000 cells/mm3, with a predicted decrease to less than 500 cells/mm3 during the next 48 hours. Category Absolute Neutrophil Count (ANC) Neutropenia < 500 cells/mm Profound Neutropenia < 1,00 cells/mm Neutropenia 10 Growth Colony Stimulating Factors (G-CSFs, or simply CSFs or "myeloid growth factors") stimulate the production of WBCs in the bone marrow. Myeloid refers to the granulocyte precursor cell, which differentiates into neutrophils, eosinophils and basophils. CSFs are given prophylactically after chemotherapy to shorten the time that a patient is at risk for infection due to neutropenia and reduce mortality from infections. They are used to prevent {or reduce) neutropenia, not for acute treatment. All patients with> 20% chance of developing chemotherapy-induced febrile neutropenia {i.e., very high risk of infection) should receive a CSF, either G- CSF (filgrastim) or pegylated G-CSF (pegfilgrastim). GM-CSF (sargramostim) is used only for stem cell transplants.  Neutropenia 11 Filgrastim Side Effects Daily treat through post-nadir bone pain recovery (until ANC > 2000-3000 Monitoring m3) Pegylated G-CSF Pegfilgrastim CBC with differential, pulmonary function, weight, Once per chemo cycle (pegfilgrastim vital signs. is pegylated, extending the half-life) Counseling tips GM-CSF Sargramostim Store in refrigerator; protect vials from Limited to use in stem cell light transplantation Administer first dose no sooner than 24 hours after chemo; can be up to 96 hours after chemo.  12 Febrile Neutropenia Patients receiving cytotoxic chemotherapy are at risk for infections from their own normal flora, including enteric bacteria and fungi, due to alterations in the GI mucosa caused by the chemotherapy drugs. Oncology patients commonly have a central venous access device {i.e., a central line) because many chemotherapy drugs are vesicants and will cause severe damage if the needle falls out of the vein. The central line can cause infection from organisms on the skin or from the insertion procedure.  13 Febrile Neutropenia  14 Febrile Neutropenia Infection can be difficult to diagnose; fever may be the only sign of infection in a neutropenic patient. Febrile neutropenia, a situation where a patient with neutropenia develops a fever, is considered a medical emergency because it may be the only sign of a severe infection. With the lack of neutrophils, the body cannot mount a typical inflammatory response, which is why common signs and symptoms like abscess formation, pus, or visible infiltrates on a chest radiograph. Empiric antibiotics are started immediately if a fever occurs.  15 Febrile Neutropenia Gram-positive and Gram-negative bacteria cause infections in febrile neutropenia, but Gram-negative bacteria have the highest risk for causing sepsis. The initial empiric antibiotics must provide adequate Gram-negative coverage, including Pseudomonas aeruqinosa. Modification of the initial empiric antibiotic regimen can be required, based on the culture results or if the clinical situation does not improve ( e.g., persistent fever).  16 Febrile Neutropenia Low risk Expected ANC < 500 cells/mm for ≤ 7 days Oral anti-pseudomonal beta- No comorbidities lactams Ciprofloxacin or levofloxacin, PLUS Amoxicillin/clavulanate, or clindamycin {if allergic to penicillin) High-risk Expected ANC ≤100 cells/mm for > 7 days IV anti-pseudomonal beta- Presence of comorbidities lactams Evidence of renal or hepatic Impairment Cefepime or (Cr Cl< 30 ml/min or LFTs> 5x ULN) Ceftazidime or Meropenem or lmipenem/cilastatin or Piperacillin/tazobactam Supportive Care in Oncology 17 I. Myelosuppression 2. Anemia  18 Anemia Hemoglobin (Hgb) levels are used to assess anemia. Normal Hgb levels are 12 - 16 g/dL for females and 13.5 - 18 g/dL for males Anemia can resolve without treatment, be treated with an RBC transfusion, or rarely, with an erythropoiesis- stimulating agent (ESA) (i.e., erythropoietin).  19 Anemia ESAs include epoetin alfa, epoetin alfa-epbx and the longer-acting darbepoetin alfa. ESAs can shorten survival and increase tumor progression (i.e., they can contribute to cancer growth). Therefore, ESAs are for palliation and are not recommended to be used in patients receiving chemotherapy with curative intent.  20 Anemia To minimize the risks of ESAs in patients with chemotherapy-induced anemia, the following requirements must be met: Use ESAs only in patients with non-myeloid malignancies where anemia is due to the effect of the chemotherapy. Upon initiation of ESA therapy, there must be a minimum of two additional months of planned chemotherapy. initiate ESAs only when the Hgb is< 10 g/dL. Use the lowest dose needed to avoid RBC transfusions. Serum ferritin, transferrin saturation (TSAT) and total iron-binding capacity (TIBC) must be assessed since ESAs will not work well to correct the anemia if iron levels are inadequate. Supportive Care in Oncology 21 I. Myelosuppression 3. Thrombocytopenia  22 Thrombocytopenia Low platelets (thrombocytes) can result in spontaneous, uncontrolled bleeding. The normal range for platelets is 150,000 - 450,000/mm 3 The risk for spontaneous bleeding is increased when the platelet count is < 10,000 cells/mm3 Platelet transfusions are indicated when the count falls below 10,000 cells/mm 3 (or< 30,000 cells/mm 3 if active bleeding is present). Chemotherapy doses may be reduced or placed on hold until the platelet count recovers. Intramuscular injections and medications that affect platelet functioning, such as NSAIDs, should be avoided in patients who are thrombocytopenic  23 A 50-year-old woman is receiving adjuvant chemotherapy for stage II breast cancer. She received her third cycle of AC (doxorubicin and cyclophosphamide) 10 days ago. Her CBC today includes WBC 600 cells/mm3, segmented neutrophils 60%, band neutrophils 10%, monocytes 12%, basophils 8%, and eosinophils 10%. She is afebrile. Which best represents this patient’s ANC? A. 600 cells/mm3 B. 360 cells/mm3 C. 240 cells/mm3 D. 420 cells/mm3 Given this ANC, which statement is most appropriate? A. The patient should be initiated on a CSF. B. The patient should begin prophylactic treatment with either a quinolone antibiotic or trimethoprim/ sulfamethoxazole. C. The patient, who is neutropenic, should be monitored closely for signs and symptoms of infection. D. Decrease the dosages of AC with the next cycle of treatment. Supportive Care in Oncology 24 II. Chemotherapy induced nausea and vomiting CINV Presentation title 25 CINV Patient factors that increase the risk of nausea and vomiting include 1. Female gender 2. Age< 5o years 3. Anxiety, depression 4. Dehydration 5. History of motion sickness 6. History of nausea and vomiting with prior regimens. Presentation title 26 CINV Agent related factors 1. High emetogenic potential: More than 90% chance of causing vomiting without antiemetic prophylaxis. 2. Moderate emetogenic potential: 30%-90% chance. 3. Low emetogenic potential: 10%-30% chance. 4. Minimal emetogenic potential: Less than 10% chance. Presentation title 27 CINV 28 Breakthrough emesis Occurs despite prophylactic treatment or necessitates additional rescue medications. Refractory emesis Emesis that occurs during treatment cycles when antiemetic prophylaxis or rescue therapy has failed in previous cycles. CINV 29 General Principles For Managing CINV General Principles 31 Prophylactic antiemetics should be administered before moderately or highly emetogenic agents and before moderately and highly emetogenic radiation. Patients receiving chemotherapeutic agents with low emetogenic potential should receive a single dose of proper options CINV prophylaxis Patients receiving chemotherapy with minimal emetogenic risk do not require prophylaxis. Antiemetics should be scheduled for delayed nausea and vomiting General Principles 32 Patients need to be protected throughout the full period of risk for nausea/vomiting: 3 days for highly emetogenic regimens 2 days for moderately emetogenic regimens Begin with an appropriate antiemetic regimen based on the emetogenicity of the chemotherapy drugs. A combination of antiemetics with different mechanisms of action is recommended to prevent acute CINV for patients receiving moderately or highly emetogenic chemotherapy, For multidrug regimens, select antiemetic therapy according to the drug with the highest emetic risk. General Principles 33 Oral and IV antiemetics can be equally effective for CINV, choice depend on patient characteristics such as ability to take oral medications, dosage form availability, and cost. Patients undergoing chemotherapy should have antiemetics available to treat breakthrough nausea and vomiting even if prophylactic antiemetics were given. If breakthrough CINV occurs despite prophylaxis, treatment with an antiemetic with a different mechanism of action is recommended. Presentation title 34  Antiemetics Palonosetron 5-HT3 antagonists Ondansetron Granisetron Aprepitant Dolasetron Fosaprepitant NK1-bloker Netupitant Rolapitant CINV treatment Corticosteroids Dexamethasone and prevention Olanzapine Dopamine Antipsychotic Prochlorperazine antagonists Haloperidol Metoclopramide Dronabinol Cannabinoids Nabilone Medications for CINV 36 5HT3 R antagonist Medications for CINV : NKR Antagonist 37 Medications for CINV 38 NKR Antagonist  39 Medications for CINV Corticosteroids: Dexamethasone  40 Medications for CINV Dopamine antagonists  41 Medications for CINV Dopamine antagonists Boxed Warnings Metoclopramide: tardive dyskinesia (TD) that can be irreversible. Discontinue metoclopramide if signs or symptoms of TD. Increased risk of developing TD with long duration of treatment and high dose.  42 Medications for CINV Cannabinoids Oral dronabinol and nabilone are used for preventing and treating refractory or delayed CINV. Side effects: Sedation, euphoria, hypotension, ataxia  43 Medications for CINV Benzodiazepines Lorazepam is used as an adjunct to antiemetic agents. Sedation is common side effects. Respiratory depression can occur with high doses or when other central depressants such as alcohol are used concomitantly.  44 A 60-year-old woman was recently given a diagnosis of advanced non–small cell lung cancer. She will begin treatment with cisplatin 100 mg/m2 plus vinorelbine 30 mg/m2. Which is the most appropriate antiemetic regimen for preventing acute emesis? A. Aprepitant plus palonosetron plus dexamethasone. B. Aprepitant plus prochlorperazine plus dexamethasone. C. Aprepitant plus granisetron plus ondansetron. D. Lorazepam plus ondansetron plus metoclopramide.  45 If the patient has anticipatory nausea and vomiting with her next cycle, which regimen would be most appropriate? A. Aprepitant plus palonosetron plus dexamethasone. B. Aprepitant plus prochlorperazine plus dexamethasone. C. Aprepitant plus granisetron plus metoclopramide. D. Aprepitant plus ondansetron plus dexamethasone plus lorazepam. THANK YOU