Management of Chemotherapy Complications

Elshami M. Elamin, MDMedical Oncologist

Central Care Cancer Centerwww.cccancer.comWichita, KS - USA

Chemotherapy: Affects the rapidly dividing cancer

cells Also affects rapidly dividing normal

cellsHairMucous membranesBlood cells

Introduction

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 THE NADIR

Effect of chemo on blood counts

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)

What is the chemo nadir?

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

Why chemo given in Cycles (q3-4 wks?)

Regim

en A

Regim

en B

Regim

en C

Day 0(Chemo Starts)

Day 7Nadir

Day 21

W.B

.C.

2.0

4.0

6.0

8.0

10.0 New

cycle

ImmediateDelayed

within daysWithin weeks

Late

Chemotherapy 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

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

Immediate Side Effects

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

Within days

Hair loss (Alopecia) Taxanes, Cisplatin, Doxo

Peripheral neuropathy Pacltaxel, Oxalipatin, Cisplatin

Dry skin or pigmentaion Nail changes Fluid retention

Docetaxel

Within weeks

Ototoxicity Cisplatin

Memory difficulties (chemo brain) Sexual dysfunction Amenorrhea Sterility MDS, leukemia

Alkyl agent (2-5yrs), cytoxan (MDS 8-10 yrs) Topoiso ll 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

Late Side effects

Delayed A.E.

(days)

Delayed A.E.

(Wks)

Late A.E.

Chemo Starts

Immediate A.E

?

Resolved

Management of a cancer patient who is undergoing

chemotherapy

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:

What is the patient status?

TREATMENT OF SIDE EFFECTS AND

COMPLICATIONS OF CANCER THERAPIES

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?

What do you need to know?

EMESIS(Nausea/Vomiting)

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

• Acute • Onset: minutes-hrs• Resolves: first 24

hrs• Delayed

• Platinum, Cytoxan, Doxo

• Onset: >24 hrs• May last for 7 days

• Anticipatory• Breakthrough/

Refractory

CINV

It is easier to preventN/V

than to treat it

Always rememberDyspepsia may mimic

nausea

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 vs Adj/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

Which anti-emetic you should chose for your patient?

High emetic risk Moderate emetic risk Low emetic risk Minimal emetic risk

Categories of Emetogenic Chemotherapy

*Don’t undertre

at

*Don’t underestim

ate

5-HT3 Antagoist

DexaAp

repi

tant

Dopamine antagonist

Lorazepam

PPI/H2-blocker

Management of Delayed Emesis

Dopamine antagonistsMetoclopramide (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 CNS2- Haloperidol

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

Prochlorperazine Metoclopramide Domperidone

Watch for Dystonic reaction

1- Diphenhydrami

ne

OR

2- Benztropine

(Cogentin)

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

Steroids

*Acute emesis:PO/IV Prior to

mod-highlyemetogenic chemo

*Delayed emesis:Days 2-3

Dexamethasone Always keep in mind its side effects

Steroids

*Hyerglycemia*HTN

*Fluid retension*PU

*Osteoporosis

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

Serotonin (5-HT3) Antagonists

Antipsychotic : Olanzapine (zyprexa)

Cannabinol: Dronabinol (marinol) 5-10 mg OR Nabilone

1-2 mg Anti-histamine:

Promethazine (phenergan) H2-Blocher or PPI

Miscellaneous

MANAGEMENT OF BREAKTHROUGH (REFRACTORY)

EMESIS

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

Breakthrough CINV

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

Breakthrough Treatment for CIN/V

Breakthrough Treatment for CIN/V

Agents from

different drug

class PRN

N/V

controlled

N/V Not controlled

Continue agent on Schedule Not PRN

Re-eval, adjust doseand or new drug

Consider change

antiemetics to

higher level for

next cycle

Second Step:

Negative bad experience with chemo 18-57% of patients

N > V Prevention:

Optimal anti-emetic with each cycle Acupuncture

Alprazolam 0.5-2 mg po tid beginning night before Or

Lorazepam 0.5-2 mg po night before and am

Anticipatory N/V

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 ….

Non-Medical measures

•Eating small frequent meals•Choice of food

• Easy on stomach•Eating food at room temperature

Dietary consult

Relaxation/systematic desensitization

Hypnosis with guided imagery

Music therapy

Spiritual

Behavioral therapy

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

Radiation-Induced N/V

CANCER-RELATED INFECTIONS

PREVENTION

TREATMENT

1. Neutropenic precaution2. Prophylactic

antimicrobials3. G-CSF

PREVENTION

Hand wash Gloves, Gowns, etc Accessing central venous

lines: Written policy Training of medical staff

Isolation

Neutropenic precaution

Prophylactic antimicrobials

Overall infection risk

Disease/Therapy

Fever/ Neutropenia

Antimicrobial prophylaxix

Low Standard chemo for solid tumor*Neutropenia < 7 d

Low None*Viral if prior HSV

Intermediate ASCTLymphomaMMPurine analog*Neutropenia 7-10 d

High*Intermediate if single agent Purine analog

*Consider fluoroquinolone (bactrim)*Consider fluconazole during neutropenia, mucositis*Antiviral during neutropenia and at least 30 days after SCT

High Allo SCTAcute leukemiaAlemtuzumabGVHD on HD steroids*Neutropenia >10 d

High *Consider fluoroquinolone (Bactrim)*Anti-fungal: I.D. consult: or consider fluconazole, Ampho-B, Voriconazole, Posaconazole, Micafungin, Itraconazole, *Antiviral during neutropenia and at least 30 days after SCT*Consider PCN and TMP/SMX (GVHD)

RISK CATOGERIES

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

Fungal 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

Anti-viral Prophylaxis

High risk groups and surveillance period :

1-6 m after SCTGVHDMinimum 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

CMV Prevention

PCP Prophylaxis(Pneumocystis Jirovecii)

Recommended Allo SC

For 6 m and while on immunosuppressants

ALL Throughout anti-

leukemic Alemtuzumab

For minimum of 2 m after it

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

Drugs of choice:TMP/SMX

Preferred If allergic or intolerant:

Desensitization or Dapsone, aerosolized Pentamidine,

Atovaquone

PCP Prophylaxis(Pneumocystis Jirovecii)

G-CSF

Regim

en A

Regim

en B

Regim

en C

Day 0(Chemo Starts)

Day 7Nadir

Day 21

W.B

.C.

2.0

4.0

6.0

8.0

10.0 New

cycle

With

G-C

SF

TREATMENT

Neutropenic Fever

Temp > 38⁰ CNeutropenia

ANC < 500 OR

Predicted decline to < 500

Look for source of infection:*Catheter sites*Skin*Lungs/Sinus*GIT*GUT

Work-up:*CBC with diff*Renal and liver function*UA +/- C/S*C-x-ray*Blood C/S x2

*ABC*Vitals Signs*Venous Access*IVF*O2*Antibiotics

Should be based on: Infection risk assessment:

High risk (inpt, co-morbid, prolonged neutropenia, pneumonia)

Low risk (outpt ) Potential VRE and ESBL (Extended Spectrum

Beta-Lactamase) MRSA status Local susceptability Organ dysfunction Drug allergy Previous antibiotics Anti-pseudomonous Bactericidal

Choice of Initial Antibiotic

Choice of Initial Empiric Antibiotic

IV monotherapy:*Primaxin*Meropenem*Zosyn*Cefepime*Ceftazidime

Oral for low risk pts*Cipro+ Augmentin or Clinda

IV combination:*Aminoglycoside + Anti-pseudom*Cipro + Antipseudom

Vanco, Linezolid, daptomycin , synercid should not be used routinely

*Daily F/U*Eval

responsein 3-5 d

RESPONDING:•Continue same antibiotic until ANC > 500 and rising

• FUO:• DC

antibiotic

• Documented infection +/- bactremia:

• Duration of therapy varies

NOT-RESPONDING:•FUO:

• Stable: • Cont. same

antibiotic• Consider

antifungal (high risk pts)

• Unstable:• Cover

anaerobes, gram neg/positive, Candida

• Consider G-CSF

• ID consult•Documented infection:

• Antibiotic/pathogen susceptibility

• Consider G-CSF• Consider

Granulocyte transfusion

Skin/Soft tissue 7-14 d

Simple bacteremia (no tissue site) Gram-negative: 10-14 d Gram-positive: 7-14 d S. aureus: 2 wks after 1st negative blood

culture & neg TEE Sinusitis: 10-21 d Bacterial pneumonia: 10-21 d

Duration of therapyBacterial Infection

Fungal: Candida: minimum 2 wks after 1st negative

blood cultue Mold (e.g. Aspergillus): minimum of 12 wks Bloodstream Yeast: > 2 wks after 1st negative

blood cultue Viral:

Localized HSV/VZV: 7-10 d (acyclovir, valacyclovir, famciclovir)

Influenza: Tamiflu X 10 d and until symptoms resolution

Duration of therapyFungal & Viral Infection

?? Catheter Removal ??

Recommended: •Septic phlebitis•Tunnel infection•Port pocket infection

Considered:•Bloodstream infection with:

• Candida• S. aureus• P. aeruginosa• Corynbacterium jeikeium• Acinetobacter• Bacillus• Atypical mycobacteria• Yeasts or molds• VRE• Stenotrophomonas

maltophilia

Serious infection associated with: Clinically apparent, serious, catheter-related infection Blood culture Gram positive (pending

identification/susceptability) Known colonization with PCN/Cephalosporin-resistant

pneumococci or MRSA Unstable pt (Hypotensive, septic shock) Soft tissue infection Pt at risk for Strep viridans bacteremia:

Severe mucositis Quinolone or Bactrim prophylaxis

Recent studies: Vanco unnecessary if beta-lactam agent is used

When to use Vancomycin as initial therapy?

*DC Vanco

in 2-3 days if a

resistant Gram-

positive not

identified

Linezolid (Zyvox) Quinupristin/

Dalfopristin (Synercid)

Daptomycin (Cubicin)

Other agents for resistant Gram-positives

*VRE

*Vano not an option

Outpatient Therapy(Low Risk Neutropenic Fever)

Who is a low risk?

Fever at homeNo co-morbiditiesAnticipated short neutropenia (<7d)Good P.S.Creatinine <2LFTs < 3 X N

Plan:2-12 hrs observationGive 1st dose and monitorDischarge planningPt educationTelephone F/U within 12-24hrs

Assessment:Careful examLab: No critical valuesCriteria for home therapy:

Consent for home care24hr care giverHome phoneAccess to ER within 1 hr

Assess for PO antibiotics:

No N/VPO toleranceNot on fluoroquinolone prophylaxi

Outpatient Therapy(Low Risk Neutropenic Fever)

Drugs of choice:• Outpt IV long-

acting antibiotic

• PO: Cipro 500mg q8h + Augmentin or Clinda

• Daily monitoring at least

for the first 3 days• Return to clinic if:

• Positive culture• New

symptoms/signs• Persistent/

recurrent fever• Oral intolerance

THANKS