management of chemotherapy complications elshami m. elamin, md medical oncologist central care...
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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
cells Hair Mucous membranes Blood 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?)
Regi
men
ARe
gim
en B
Reg
imen
C
Day 0(Chemo Starts)
Day 7Nadir
Day 21
W.B
.C.
2.0
4.0
6.0
8.0
10.0 New
cycle
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
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?
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?
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
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 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
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
controlle
d
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
Hand wash Gloves, Gowns, etc Accessing central
venous lines: Written policy Training of medical staff
Isolation
Neutropenic precaution
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 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
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)
Regi
men
ARe
gim
en B
Reg
imen
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
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