Supportive Care for Oncologic Complications

Common Terminology Criteria for Adverse Events

CTCAE

CTCAE

• Developed by the National Cancer Institute

• Descriptive terminology used for adverse event reporting

grade 1

Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated

Grade 2

Moderate; minimal, local or noninvasive intervention indicated; limiting age appropriate instrumental ADL

Grade 3

Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care ADL

Grade 4

Life-threatening consequences; urgent intervention indicated

Grade 5

death related to AE

myelosuppression

decrease in bone marrow activity that results in decrease in WBC, RBC and plts

dose limiting

Myelosuppression is the most common ____________ toxicity with chemotherapy.

nadir

lowest blood count

6-12 hrs

What is the lifespan of neutrophils?

5-10 days

What is the lifespain of platelets?

120 days

What is the lifespan of erythrocytes?

neutrophil

type of WBC involved in acute immune response

50-60%

What % of WBC are neutrophils?

mature

segmented

almost mature

bands

neutropenia

-can increase risk of infection, hospitalization and mortality

-can delay delivery of full dose-chemo

-can increase cost of cancer care

absolute neutrophil count

ANC

ANC

reps the # of WBCs that are neutrophils

1,000-1,500 mm2

ANC must be above ____________ to give most chemo.

febrile neutropenia

-ANC < 500 OR

granulocyte-colony stimulating factor (G-CSF)

• Stimulates proliferation and differentiation of progenitors already

committed to the neutrophil lineage

• Activates the phagocytic activity of mature neutrophils (i.e. activation) and prolongs their survival in the circulation.

• Mobilizes hematopoietic stem cells to increase their concentration in peripheral blood

Neupogen

Filgrastim

5 mcg/kg subq until post-nadir ANC recovery to near normal/normal

What is the dosing of Filgrastim?

AEs of Filgrastim (Neupogen)

• Bone pain (10-30%)- treat with NSAID or loratadine

• Allergic reactions

• Splenic rupture (rare)

monitoring of Filgrastim

-CBC with diff

-severe abdominal pain (sign of splenic rupture)

kinetics of Filgrastim

-T1/2= 3-5 hrs

-Onset of action: 1-2 days

-Admin: IV or SC

Neulasta

Pegfilgrastim

6 mg subq once per chemo cycle

-start next day or up to 3-4 days after completion of chemo

-should be at least 12 days between it and the next dose of chemo

What is the dosing of Pegfilgastim (Neulasta)?

15-80 hrs

What is the T1/2 of Pegfilgrastim (Neulasta)?

-prefilled syringe

-Neulasta OnPro device

How is Pegfilgrastim supplied?

10-50%

What is the incidence of febrile neutropenia in solid tumors in pts?

80-100%

What is the incidence of febrile neutropenia in hematologic malignancies in pts?

febrile neutropenia risk

risk due to breakdown in protective skin barriers, alterations in GI mucosa and use of chemo port

bone pain

What is the most common AE for Filgrastim (Neupogen)?

NSAID or Loratadine

How do you treat the bone pain with Filgrastim?

positive

More cases of febrile neutropenia have gram ___________ organisms.

negative

gram _____________ organisms in febrile neutropenia are associated with mortality rates.

fungal infections

more common in pts who have been receiving broad-spectrum abx and/or steroids in febrile neutropenia

parasitic infections (P. jirovecii and T. gondi)

most common in pts with febrile neutropenia with hematologic malignancies and on high dose corticosteroids

1) complete infectious work up

2) determine in pt is low-risk versus high-rish

3) start with broad spectrum abx with ANTI-PSEUDOMONAS activity

4) if no response, broaden coverage to include organisms not covered by initial therapy (MRSA and fungus)

What is the treatment for febrile neutropenia?

outpatient tx

If a pt is low risk febrile neutropenia where are they treated?

inpatient tx

If a pt is high risk febrile neutropenia where are they treated?

• Cefepime

• Antipseudomonal carbapenem

- Imipenem/cilastatin

- Meropenem

• Piperacillin/tazobactam

What are the IV antibiotics for febrile neutropenia?

• Ciprofloxacin plus amoxicillin/clavulanate^ (preferred)

• Moxifloxacin (insufficient P. aeruginosa coverage)

What are the oral antibiotics for febrile neutropenia?

Clindamycin

If a pt has a PCN allergy and febrile neutropenia and is getting oral abx what can you give?

S. aureus

Which of the following is a gram post organism associated with febrile neutropenia?

A. E. coli

B. K. pneumoniae

C. P. aeruginosa

D. S. aureus

presence of urinary catheter increases risk of febrile neutropenia

Which of the following is true regarding febrile neutropenia?

A. P. aeruginosa has low mortality in febrile neutropenia pts

B. fungal coverage is needed as part of initial empiric coverage for all pts with febrile neutropenia

C. IV antibiotics are required for tx of febrile neutropenia

D. presence of urinary catheter increases risk of febrile neutropenia

pt with 1 time oral temp of 38.3 C and ANC of 400

Which of the following pts has febrile meutropenia?

A. pt with ANC of 350

B. pt with 1 time oral temp of 38.3 C and ANC of 400

C. pt with 1 time oral temp of 38 C and ANC of 450

D. pt with 1 time oral temp of 39 C

Ceftazidime and Meropenem

Whic of the following meds would be appropriate use for empiric tx of febrile neutropenia?

A. Ceftriaxone

B. Ceftazidime

C. Ertapenem

D. Meropenem

30-90%

What % of pts with cancer experience chemo associated anemia?

-decreased production of RBCs

-increased destruction of RBCs

-blood loss

What are the 3 pathophysiologic origins of chemo associated anemia?

12-13

What is normal Hgb?

consider transfusion or ESA

If a pt has high risk anemia and is asymptomatic what is the tx?

tx with transfusion or ESA

If a pt is symptomatic or Hgb < 7 with anemia in cancer what is the tx?

symptomatic

-tachycardia

-tachypenea

-chest pain

-dyspnea on exertion

-lightheadedness

-syncope

-severe fatigue

ESA

What do you use in anemic chemo pts who are on palliative tx?

RBC transfusion

What do you use in anemic chemo pts who are on curative tx?

risks of ESAs

-increase thrombotic events

-increase BP

-possible decreased survival

-time to tumor progression shortened

risks of RBC transfusion

-transfusion reaction

-iron overload

-avoid transfusion

-gradual improvement

What are the goals of ESAs in the cancer setting?

-transfusion reaction

-iron overload

What is the risk with RBC transfusions?

-rapid improvement in Hgb and Hct

-rapid improvement in anemia-related symptoms

What are the goals with RBC transfusion?

ESAs

-epoetin alfa (Procrit/Epogen/Retacrit)

-darbopoetin alfa (Aranesp)

MOA of ESAs

-proteins that exert same effects as endogenous erythropoietin

-stimulates production and differentiation of RBC

3x weekly or weekly

What is the dosing of Epoetin?

IV/SC

What is the admin of ESAs?

every week, 2 weeks or 3 weeks

What is the dosing of Darbepoetin?

make sure the pt has adequate iron stores

What is important when giving ESAs?

AEs of ESAs

-Boxed Warnings: increased risk of VTE, MI, stroke and death; especially if treatment goal Hgb>11 g/dL

-Contraindication: uncontrolled HTN

• Arthralgia

• Injection site reaction

• Edema

ADME of ESAs

T1/2: darbepoetin 24-144 hrs; epoetin 4-13 hrs

acute CINV

occurs < 24 hrs after chemo

delayed CINV

occurs > 24 hrs after chemo

anticipatory CINV

occurs before chemo

breakthrough CINV

emesis despite prophylaxis that requires rescue tx

refractory CINV

poor response to prior regimens

serotonin and substance P

What is the major neurotransmitter in acute CINV?

substance P and dopamine

What is the major neurotransmitter in delayed CINV?

GABA

What is the major neurotransmitter in anticipatory CINV?

principles of CINV tx

- Primary goal to prevent emesis throughout period of emetic risk

• 2 days for moderately emetic regimen

• 3 days for highly emetic regimen

- Selection of treatment should be based on medication with highest emetogenicity

- Consider lifestyle measures to help alleviate nausea/vomiting as well as pharmacotherapy

-Olanzapine 2.5-10 mg orally

-NK1 RA

-5-HT3 RA

-Dexamethasone 12 mg po/IV

*option to omit olanzapine or NK1 RA for 3 drug regimen per NCCN guidelines

What is the pre-chemo emesis prevention tx for high emetic risk parenteral chemo acute and delayed emesis prevention?

-Olanzapine 2.5-10 mg QHS

-Dexamethasone 8mg PO QD

-*Aprepitant 80 mg on days 2, 3 (if PO given on day 1)

What is the tx for high emetic risk parenteral chemo acute and delayed emesis prevention on days 2, 3 and 4?

-5-HT3-RA

-Dexamethasone IV/PO

What is given on day 1 in option 1 for the moderate emetic risk parenteral chemo acute and delayed emesis prevention?

dexamethasone 8 mg PO on days 2,3

OR

5-HT3-RA monotherapy for days 2,3

What is given on days 2,3 in option 1 for moderate emetic risk parenteral chemo acute and delayed emesis prevention?

1) olanzapine PO

2) Palonosetron IV

3) Dexamethasone IV/PO

What is given on day 1 in option 2 of moderate emetic risk parenteral chemo-acute and delayed emesis prevention?

olanzapine PO on days 2,3

What is given on days 2,3 in option 2 of moderate emetic risk parenteral chemo-acute and delayed emesis prevention?

1) NK1 RA

2) 5-HT3-RA

3) Dexamethasone PO/IV

What is given on day 1 in option 3 of moderate emetic risk parenteral chemo acute and delayed emesis prevention?

1) Dexamethasone IV/PO on days 2,3

2) Aprepitant PO on days 2,3 (if PO given on day 1)

What is given on days 2,3 of moderate emetic risk parenteral chemo acute and delayed emesis prevention?

(SINGLE AGENT)

-Dexamethasone PO/IV

-Ondansetron PO

-Prochlorperazine PO

What is the low emetic risk parenteral chemo emesis prevention treatment?

nothing

What is the minimal emetic risk parenteral chemo emesis prevention tx?

start before anticancer tx and continue daily on each daily of anticancer therapy

-5HT3 RA (choose one)

*Granisetron 1-2 mg PO daily or 3.1 mg/24 hrs transdermal patch every 7 days

*ondansetron 8-16 mg PO daily

OR

-Olanzapine 2.5-10 PO QHS

What is the oral chemo emesis prevention tx for moderate to high emetic risk?

breakthrough tx for CINV

1. Add an agent from a different drug class to current regimen

- Olanzapine (preferred)

- Lorazepam

- Dronabinol

- Haloperidol

- Metoclopramide

- Scopolamine

- Promethazine/prochlorperazine

- 5-HT3-RA

- Dexamethasone

2. If controlled, continue breakthrough medication on a schedule, NOT prn

3. If uncontrolled, continue dose adjustments or adding an agent from a different drug class

4. Reassess both day 1 and post-chemotherapy regimen on next cycle

Lorazepam 0.5-1 mg

Olanzapine 2.5-5mg PO

What are the meds given for anticipatory emesis prevention/tx?

Cimvanti

Aprepitant IV

Emend

Aprepitant PO

Emend

Fosaprepitant IV

Neurokinin-1 Receptor Antagonists

Inhibits substance P at neurokinin 1 (NK1) receptor- Augments the antiemetic activity of 5-HT3 RA and dexamethasone

prevention

Neurokinin-1 Receptor Antagonists are used for the _________ of CINV. (largest benefit with delayed CINV)

Aprepitant

• IV emulsion less AE than fosaprepitant

• Oral requires dose on day 1-4

Fosaprepitant

• Given only on day 1

• Higher risk of infusion-related reaction