5. 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
6. 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)
7. 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
8. 10.0
8.0
6.0
W.B.C.
4.0
2.0
Day 0
(Chemo Day 7 Day 21
Starts) Nadir
10. Immediate Side Effects
Allergic reactions:
Infusion-related
Rituximab
Anaphylactic
Burning sensation or pain at the site of infusion
Irritant
Vesicant
Urine discoloration
Doxorubicin ļ Red
Mitoxantrone ļ Blue
11. Immediate Side Effects
Acute emesis (Nausea/Vomiting):
Within few min ā 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
12. Within days
Delayed-onset emesis:
> 24 hrs after chemo ā 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
18. Management of a cancer
patient who is undergoing
chemotherapy
19. What is the patient status?
SOAP:
Subjective:
Fever, pain, S.O.B., cough, bleeding, diarrhea etc ā¦
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:
21. 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?
24. Causes of N/V in cancer patients
Chemo Uremia
RT Opiates
Bowel obstruction Gastroparesis
Brain mets (Vincrestine)
Electrolytes imbalance Psycophysiologic:
Hypercalcemia, Anxiety
Hyponatremia, Anticipating N/V
Hyperglycemia
25.
26.
27.
28. CINV
ā¢ Acute
ā¢ Onset: minutes-hrs
ā¢ Resolves: first 24 hrs It is easier to prevent
N/V
ā¢ Delayed than to treat it
ā¢ Platinum, Cytoxan, Doxo
ā¢ Onset: >24 hrs
ā¢ May last for 7 days
ā¢ Anticipatory
ā¢ Breakthrough/Refractory Always
remember
Dyspepsia may
mimic nausea
29. 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
34. 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
35. 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
37. Steroids
Dexamethasone
Improve efficacy of 5-HT3 antagonists
With Aloxi for moderate risk:
8 mg d1 enough
No need on d 2-3
*Acute emesis:
Do Not use if chemo include steroids PO/IV Prior to
e.g. ESHAP mod-highly
Contra-indicated with: emetogenic chemo
IL-2 *Delayed emesis:
IFN Days 2-3
39. 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
40. Miscellaneous
Antipsychotic :
Olanzapine (zyprexa)
Cannabinol:
Dronabinol (marinol) 5-10 mg OR Nabilone 1-2 mg
Anti-histamine:
Promethazine (phenergan)
H2-Blocher or PPI
42. 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
43. 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
44. Breakthrough Treatment for CIN/V
Second Step:
Continue agent on
Schedule Not PRN
Agents Consider
from change
different antiemetics
drug class to higher
PRN level for
next cycle
Re-eval, adjust dose
and or new drug
46. 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
47. It is not always medication to do it ā¦
It is not always doctors and nurses to
do it ā¦
It is most of the time the patient to
do it ā¦
57. RISK CATOGERIES
Overall infection Disease/Therapy Fever/ Antimicrobial prophylaxix
risk Neutropenia
Low Standard chemo for Low None
solid tumor *Viral if prior HSV
*Neutropenia < 7 d
Intermediate ASCT High *Consider fluoroquinolone
Lymphoma *Intermediate if (bactrim)
MM single agent *Consider fluconazole during
Purine analog Purine analog neutropenia, mucositis
*Neutropenia 7-10 d *Antiviral during neutropenia and at
least 30 days after SCT
High Allo SCT High *Consider fluoroquinolone
Acute leukemia (Bactrim)
Alemtuzumab *Anti-fungal: I.D. consult: or
GVHD on HD consider fluconazole, Ampho-B,
steroids Voriconazole, Posaconazole,
*Neutropenia >10 d Micafungin, Itraconazole,
*Antiviral during neutropenia and at
least 30 days after SCT
*Consider PCN and TMP/SMX
(GVHD)
58. 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
59. 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
60. 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
61. PCP Prophylaxis
(Pneumocystis Jirovecii)
Recommended Considered
Allo SC Fludara, T-cell depleting agents
For 6 m and while on Until CD4 > 200
immunosuppressants Prolonged steroids (e.g. Pred >
ALL 20mg qd x > 4 wks0
Throughout anti-leukemic
Temodar + RT
Alemtuzumab
ASCT
For minimum of 2 m after it
For 3-6 m after it
62. PCP Prophylaxis
(Pneumocystis Jirovecii)
Drugs of choice:
TMP/SMX
Preferred
If allergic or intolerant:
Desensitization or
Dapsone, aerosolized Pentamidine, Atovaquone
66. Neutropenic Fever
Look for source of infection:
*Catheter sites
*Skin
*Lungs/Sinus
Temp > 38ā° C *GIT *ABC
Neutropenia *GUT *Vitals Signs
ANC < 500 *Venous Access
OR *IVF
Predicted *O2
Work-up: *Antibiotics
decline to < 500
*CBC with diff
*Renal and liver function
*UA +/- C/S
*C-x-ray
*Blood C/S x2
67. 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
68. Choice of Initial Empiric Antibiotic
IV monotherapy:
*Primaxin
IV combination:
*Meropenem
*Aminoglycoside + Anti-pseudom
*Zosyn
*Cipro + Antipseudom
*Cefepime
*Ceftazidime
Oral for low risk pts
*Cipro+ Augmentin or Clinda
Vanco, Linezolid, daptomycin , synercid should not be used routinely
69. NOT-RESPONDING:
ā¢FUO:
ā¢Stable:
ā¢Cont. same
antibiotic
RESPONDING:
ā¢Consider
ā¢Continue same
antifungal (high
antibiotic until ANC >
risk pts)
500 and rising
ā¢Unstable:
ā¢FUO: *Daily F/U ā¢Cover
ā¢DC *Eval anaerobes, gram
antibiotic
response neg/positive,
ā¢Documented
infection +/-
in 3-5 d Candida
ā¢Consider G-CSF
bactremia:
ā¢ID consult
ā¢Duration
ā¢Documented infection:
of therapy
ā¢Antibiotic/pathogen
varies
susceptibility
ā¢Consider G-CSF
ā¢Consider Granulocyte
transfusion
70. 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
71. 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
73. When to use Vancomycin as initial therapy?
Serious infection associated with:
Clinically apparent, serious, catheter-related infection
Blood culture ļ 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
Severe mucositis resistant Gram-
positive not
Quinolone or Bactrim prophylaxis identified
Recent studies: Vanco unnecessary if beta-lactam agent is used
74. Other agents for resistant Gram-positives
Linezolid (Zyvox)
*VRE
Quinupristin/Dalfopristin
*Vano not (Synercid)
an option Daptomycin (Cubicin)
75. Outpatient Therapy
(Low Risk Neutropenic Fever)
Who is a low Assessment:
risk? Careful exam Plan:
Fever at home Lab: No critical values 2-12 hrs
Criteria for home therapy:
No co- observation
Consent for home care
morbidities 24hr care giver Give 1st dose
Anticipated Home phone and monitor
short Access to ER within 1 Discharge
hr
neutropenia planning
Assess for PO antibiotics:
(<7d) No N/V Pt education
Good P.S. PO tolerance Telephone F/U
Creatinine <2 Not on within 12-
fluoroquinolone
LFTs < 3 X N 24hrs
prophylaxi
76. Outpatient Therapy
(Low Risk Neutropenic Fever)
ā¢ Daily monitoring at least
Drugs of choice: for the first 3 days
ā¢ Outpt IV long- ā¢ Return to clinic if:
acting antibiotic ā¢ Positive culture
ā¢ PO: Cipro 500mg ā¢ New symptoms/signs
q8h + Augmentin ā¢ Persistent/recurrent
or Clinda fever
ā¢ Oral intolerance
