Onco exam 1: Myelosupression, CINV, Febrile Neutropenia

Myelosuppression def

decreased bone marrow production of one or more hematopoietic cell lines

• so RBC, Granulocytes(Eosinophils, basophils, and

  neutrophils), and Platelets are effected

What factors affect myelosupression?

Bone marrow kinetics, cell cycle specificity, route of admin, prior bone marrow damage

Shortest to Longest life span bone marrow kinetics

Neutrophil < Platelet < RBC

neutrophil first to decline in myelosuppression

Blood cell disorder name for: RBC, Platelets, WBC, and all of them

RBC- anemia

Platelets- Thrombocytopenia

WBC- Leukopenia

Pancytopenia – all blood cell lines are abnormally low

Neutropenia, important, ANC severe count

abnormally low neutrophil count

Fever + neutropenia = oncologic emergency

severe: < 500 cells/mm3

Lowest point in myelosuppression

Nadir; reached 7-14 days after myelosuppressive chemotherapy

G-CSF moa and goal

Stimulates the proliferation, differentiation, and activation of neutrophil precursors, increasing neutrophil production and function

goal: shorten DURATION of neutropenia which reduces risk and complications associated with that

G-CSF Primary Prophylaxis when to start and in who

Start in 1st chemotherapy cycle for prevention of neutropenia

start in pts who have a 20>= risk of febrile neutropenia

G-CSF Secondary Prophylaxis when and who

Starts in subsequent cycles after patient develops febrile neutropenia in a previous cycle

start in pts with previous neutropenic complication in previous cycle

Filgrastim vs Pegfilgrastim vs Eflapregrastim

Filgrastim→ short duration and given continous through nadir

Pegfilgrastim/Eflapregrastim→ long and given once 24-48/24 hr after chemo

• make sure NOT using same day as chemo

Trilaciclib indication and moa

used for chemo therapy induced myelosuppression

moa: CDK4/6 inhibitor (stops cells in G1 phase)

Chemotherapy-Induced Thrombocytopenia severe number and why

Platelets < 10,000 cells/mm3→ Increased risk of gastrointestinal bleed/intracranial hemorrhage

• need to be transfused if going thru surgery or biopsy

• transfusion for non bleeding pts at this point

when to give Platelet transfusion earlier?

active bleeding, Planned invasive procedure, higher bleeding risk

• prophylactic

Romiplostim indication and moa

Immune thrombocytopenia

Thrombopoietin receptor agonist (TPO-RA)

Anemia treatment

Erythropoietin stimulating agents and RBC transfusion

pretty rapid 1 unit= +1 g/dL

Indications For Blood Transfusion in anemia

Symptomatic patient (SOB, dyspnea, tachy, AMS, cardiac ischemia)

if asymptomatic w comorb

consider when Hgb < 7 g/dL in hemodynamically stable hospitalized adults

Erythropoiesis Stimulating Agents (ESAs) moa

Induce proliferation and differentiation along reticulocyte pathway to mature erythrocytes (stimulate RBC production)

ESA for Chemotherapy-Induced Anemia

• only use it for PALLIATIVE, not curative

• NO if Hgb>10

ESA drugs, dosing duration and ADE

Epoetin alfa→ 4 wks therapy

Darbepoetin alfa→ 6 wks therapy

ADE: Hypertension, thrombosis,

Absolute Neutrophil Count Equation

slide 6 nav

Neutropenia levels (severe, profound)

neutropenia: ANC < 1500 cells/ μL

severe: ANC < 500 cells/μL, OR ANC < 1000 cells/μL and predicted to decline

Profound: ANC < 100 cells/μL

highest infection risk for neutropenia

with profound and prolonged neutropenia

Febrile Neutropenia definition

Severe neutropenia + single oral temperature ≥ 101°F OR ≥ 100.4°F for 1 hour

FEVER is only sign of infection, if associated with neutropenia→ emergency

Factors Predisposing Patients to Infections

Neutropenia, Mucosal barrier injury(i.e. portal entry), Dysbiosis(alteration of gut microbiome + overgrowth)

What is high risk vs low risk in terms of bacteria, tumor type, fever duration

High: gram (-) like psuednomas; hematologic malignancies, >7 days fever,

Low: gram +, solid tumors, < 7 days fever

there are scoring tools to help

Principles of Antimicrobial Therapy in cancer pts

fever + neutropenia→ ASSUME its infection

assess within 15 min

start med within 60 min

Empiric antimicrobial regimens should always cover Pseudomonas aeruginosa

Empiric Therapy in High-Risk Patients febrile neutropenia

monotherapy with IV antipseudomonal beta-lactam

Piperacillin/tazobactam, Cefepime, Meropenem, Imipenem/cilastatin

NO VANCOMYCIN

when to add vancomycin to empiric therapy for high risk pts with febrile neutropenia

if MRSA, Skin and soft-tissue infection, pneumonia, sus IV catheter related infection, gram +, clinical instability

Empiric Therapy in Low-Risk Patients febrile neutropenia

IV admin at med facility then PO fluoroquinolone-based regimens

• Ciprofloxacin + amoxicillin/ clavulanate (preferred)

• Ciprofloxacin + clindamycin

• Levofloxacin/ Moxifloxacin

CANT DO PO if used fluoroquinolone prophylaxis

Duration of therapy for febrile neutropenia documented and undocumented infections

documented: standard course of therapy has been completed, and ANC is ≥ 500 cells/μL

not documented: either fever gone for >2 days and ANC>500 OR discontinue >3 days of IV antibiotics and fever gone for >2 days irrespective of ANC

Peripheral Pathway of NV in chemo

Acute→ 5-HT3 receptors stimulation of vagal nerve thus signaling area postrema in medulla to stimulate emesis

Central Pathway of NV in chemo

Delayed: substance P from neurons binds to NK-1 receptors to induce emesis

Acute, Delayed, Anticipatory, Breakthrough, Refractory NV

Acute→ within 24 hrs thru serotonin receptors

Delayed→ after 24 hrs thru NK-1 receptors

Anticipatory→ occurs before chemo; physiologically related to memory of previous cycles

Breakthrough→ occurs within 5 days with anti-emetic meds

Refractory→ persistent, meds dont work after therapy fails

pt related vs treatment related risk factors of CINV

pt: <50yo, female>, lil-no alc

treatment: prior CINV, Concomitant drug therapy (ex. Opioids), high potential w chemo regimen

Which have high Emetogenicity

AC combo → chemotherapy regimen that contains an anthracycline and cyclophosphamide

Cisplatin

Fam-trastuzumab deruxtecan

Serotonin receptor antag drugs, moa, use and class side effects

Drugs: Ondansetron, Granisetron, Palonosetron

Blocks serotonin

PREVENTS acute, TREATMENT of breakthru and refractory

side effects: constipation, QTc prolongation(>16mg IV), serotonin syndrome

NK1 receptor antag drugs, moa and use

Drugs: Fosaprepitant, Aprepitant, Rolapitant, Netupitant/palonosetron(combo)

Inhibits the substance P/NK1 receptor

PREVENTS of acute and delayed phases of CINV

Corticosteroids moa, use, side effects

unknown moa,

Prevention of acute and delayed in combo; treatment of breakthrough and refractory CINV

side effects: insomnia,dyspepsia

Dexamethasone when to use and when not to

Steroid with most literature in CINV

use in combo

dont use if steroid is part of treatment regimen; dont use for 3-5 days before and 90 days after CAR T cell therapy

Dopamine Receptor antag drugs, moa, use, side effects

Metoclopramide, Olanzapine, Haloperidol (all dopamine2 RA)

moa: blocks Serotonin, dopamine-1, dopamine-2, histamine and alpha 1 adrenergic

Prevention and treatment of breakthrough / refractory

side effect: Extrapyramidal Symptoms (EPS)

Olanzapine additional use, and side effect

class use: breakthrough / refractory

additional: acute and delayed

Qtc prolong anticholinergic effects (similar to halperidol)

Metoclopramide dlt

use <12 weeks due to increased risk of tardive dyskinesia

EPS symptom treatment

intermittent involuntary spasmodic contractions of muscles

Treatment of dystonic reactions: diphenhydramine and benztropine

Benzodiazepine drugs, moa, use

moa: Enhancement of the inhibitory effect of GABA-A receptors

Treatment of breakthrough, refractory, or anticipatory CINV

Lorazepam→ BBW for resp depression

Antihistamines drugs moa, use, side effects

Competitive inhibition of H1 receptors on cells in the GI tract, and vomiting center (NTS)

Breakthrough, refractory CINV and prevention of EPS with D2RA

Anticholinergic side effects

drug: Scopolamine (can cause depression)

Prevention of CINV Day 1 high emetogencity

1. Olanzapine 2.5-10 mg once

2. NK1 RA (Choose one)

3. 5-HT3 RA (Choose one)

4. Dexamethasone 12 mg IV/PO once

Prevention of CINV Day 2-4 high emetogencity

1. Olanzapine 2.5-10 mg once daily at bedtime

2. Aprepitant 80 mg PO daily on days 2-3 (If aprepitant PO used on day 1)

3. Dexamethasone 8 mg IV/PO daily on days 2,3,4

Prevention of CINV Day 1- Moderate EC

5-HT3 RA (Choose one) and Dexamethasone 12 mg IV/PO once

OR

Olanzapine 2.5-10 mg PO once, Palonosetron 0.25 mg IV once, Dexamethasone 12 mg IV/PO once

OR

NK1 RA (Choose one), 5-HT3 RA (Choose one), Dexamethasone 12 mg IV/PO once

Prevention of CINV Day 2-3- Moderate EC

Dexamethasone 8 mg IV/PO daily or 5-HT3 RA monotherapy

OR

Olanzapine 2.5-10 mg PO daily at bedtime

OR

Aprepitant 80 mg PO daily on days (if aprepitant PO used day 1) +/- Dexamethasone 8 mg IV/PO daily

Management of Breakthrough CINV

add one agent from a different drug class than current scheduled preventative regimen

pref is Olanzapine

Approaches to Refractory CINV

add agents from different drug classes until controlled, dose optimizations

Prevention of Anticipatory CINV

Lorazepam the night before + repeat dose 1-2 hrs before chemo dose

or Olanzapine single dose

pref is Non-pharmacologic approaches like breathing exercises and stuff