Management of Chemotherapy
Complications
Elshami M. Elamin, MD
Medical Oncologist
Central Care Cancer Center
www.cccancer.com
Wichita, KS - USA
Introduction
 Chemotherapy:
 Affects the rapidly dividing cancer cells
 Also affects rapidly dividing normal cells
 Hair
 Mucous membranes
 Blood cells
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
THE NADIR
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)
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
10.0
W.B.C.
8.0
6.0
4.0
2.0
Day 0
(Chemo
Starts)
Day 7
Nadir
Day 21
Chemotherapy Side Effects
Immediate
Delayed
within days
Within weeks
Late
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
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
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
Within weeks
 Hair loss (Alopecia)
 Taxanes, Cisplatin, Doxo
 Peripheral neuropathy
 Pacltaxel, Oxalipatin, Cisplatin
 Dry skin or pigmentaion
 Nail changes
 Fluid retention
 Docetaxel
Late Side effects
 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
Delayed
A.E.
Immediate
A.E
(days)
Delayed
A.E.
Chemo
Starts
?
(Wks)
Late A.E.
Management of a cancer
patient who is undergoing
chemotherapy
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:
TREATMENT OF SIDE EFFECTS
AND COMPLICATIONS OF
CANCER THERAPIES
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?
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
CINV
• Acute
• Onset: minutes-hrs
• Resolves: first 24 hrs
• Delayed
It is easier to prevent
N/V
than to treat it
• Platinum, Cytoxan, Doxo
• Onset: >24 hrs
• May last for 7 days
• Anticipatory
• Breakthrough/Refractory
Always
remember
Dyspepsia may
mimic nausea
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 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
Categories of Emetogenic
Chemotherapy




High emetic risk
Moderate emetic risk
Low emetic risk
Minimal emetic risk
*Don’t
undertreat
*Don’t
underestimate
5-HT3 Antagoist
Dexa
Aprepitant
Lorazepam
PPI/H2-blocker
Dopamine
antagonist
Management of
Delayed Emesis
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
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
Watch for Dystonic reaction
 Prochlorperazine
 Metoclopramide
 Domperidone
Steroids
 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
*Acute emesis:
PO/IV Prior to
mod-highly
emetogenic chemo
*Delayed emesis:
Days 2-3
Steroids
 Dexamethasone
 Always keep in mind its side effects
*Hyerglycemia
*HTN
*Fluid retension
*PU
*Osteoporosis
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
Miscellaneous
 Antipsychotic :
 Olanzapine (zyprexa)
 Cannabinol:
 Dronabinol (marinol) 5-10 mg OR Nabilone 1-2 mg
 Anti-histamine:
 Promethazine (phenergan)
 H2-Blocher or PPI
MANAGEMENT OF
BREAKTHROUGH
(REFRACTORY)
EMESIS
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
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
Breakthrough Treatment for CIN/V
Second Step:
Continue agent on
Schedule Not PRN
Agents
from
different
drug class
PRN
Consider
change
antiemetics
to higher
level for
next cycle
Re-eval, adjust dose
and or new drug
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 po tid beginning night before
Or
 Lorazepam 0.5-2 mg po night before and am
 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
Behavioral therapy
 Relaxation/systematic desensitization
 Hypnosis with guided imagery
 Music therapy
 Spiritual
Radiation-Induced N/V
 R.T. - upper abdomin:
 Pretreatment daily:
 Granisetron 2 mg qd OR
 Ondansetron 8 mg bid
 TBI:
 +/- Dexa 4 mg qd
 Pretreatment:
 Granisetron 2 mg qd OR
 Ondansetron 8 mg bid-tid
 +/- Dexa 4 mg qd
 ChemoRT:
 CIN/V protocol
CANCER-RELATED INFECTIONS
PREVENTION
TREATMENT
PREVENTION
1. Neutropenic precaution
2. Prophylactic antimicrobials
3. G-CSF
Neutropenic precaution
 Hand wash
 Gloves, Gowns, etc
 Accessing central venous lines:
 Written policy
 Training of medical staff
 Isolation
Prophylactic antimicrobials
RISK CATOGERIES
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
ASCT
Lymphoma
MM
Purine 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 SCT
Acute leukemia
Alemtuzumab
GVHD 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)
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
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
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
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
PCP Prophylaxis
(Pneumocystis Jirovecii)
 Drugs of choice:
 TMP/SMX
 Preferred
 If allergic or intolerant:
 Desensitization or
 Dapsone, aerosolized Pentamidine, Atovaquone
G-CSF
10.0
W.B.C.
8.0
6.0
4.0
2.0
Day 0
(Chemo
Starts)
Day 7
Nadir
Day 21
TREATMENT
Neutropenic Fever
Temp > 38⁰ C
Neutropenia
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
Choice of Initial Antibiotic
 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 Empiric Antibiotic
IV monotherapy:
*Primaxin
*Meropenem
*Zosyn
*Cefepime
*Ceftazidime
IV combination:
*Aminoglycoside + Anti-pseudom
*Cipro + Antipseudom
Oral for low risk pts
*Cipro+ Augmentin or Clinda
Vanco, Linezolid, daptomycin , synercid should not be used routinely
RESPONDING:
•Continue same
antibiotic until ANC >
500 and rising
•FUO:
•DC
antibiotic
•Documented
infection +/bactremia:
•Duration
of therapy
varies
*Daily F/U
*Eval
response
in 3-5 d
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
Duration of therapy
Bacterial Infection
 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 therapy
Fungal & Viral 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
?? Catheter Removal ??
Considered:
Recommended:
•Septic phlebitis
•Tunnel infection
•Port pocket infection
•Bloodstream infection with:
•Candida
•S. aureus
•P. aeruginosa
•Corynbacterium jeikeium
•Acinetobacter
•Bacillus
•Atypical mycobacteria
•Yeasts or molds
•VRE
•Stenotrophomonas maltophilia
When to use Vancomycin as initial therapy?
 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)
*DC
 Soft tissue infection
Vanco in 2-3
 Pt at risk for Strep viridans bacteremia:
days if a
resistant Gram Severe mucositis
positive not
 Quinolone or Bactrim prophylaxis
identified
 Recent studies: Vanco unnecessary if beta-lactam agent is used
Other agents for resistant Gram-positives
*VRE
*Vano not
an option
 Linezolid (Zyvox)
 Quinupristin/Dalfopristin
(Synercid)
 Daptomycin (Cubicin)
Outpatient Therapy
(Low Risk Neutropenic Fever)
Who is a low
risk?
Fever at home
No comorbidities
Anticipated
short
neutropenia
(<7d)
Good P.S.
Creatinine <2
LFTs < 3 X N
Assessment:
Careful exam
Lab: No critical values
Criteria for home therapy:
Consent for home care
24hr care giver
Home phone
Access to ER within 1
hr
Assess for PO antibiotics:
No N/V
PO tolerance
Not on
fluoroquinolone
prophylaxi
Plan:
2-12 hrs
observation
Give 1st dose
and monitor
Discharge
planning
Pt education
Telephone F/U
within 1224hrs
Outpatient Therapy
(Low Risk Neutropenic Fever)
Drugs of choice:
• Outpt IV longacting 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