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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


         8.0


         6.0
W.B.C.




         4.0


         2.0



               Day 0
               (Chemo    Day 7           Day 21
               Starts)           Nadir
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
Mucositis
MUCOSITIS
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
        Immediate                A.E.
           A.E
                                (days)




                                      Delayed
    Chemo                              A.E.
    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)
23
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
CINV
• Acute
  • Onset: minutes-hrs
  • Resolves: first 24 hrs          It is easier to prevent
                                              N/V
• Delayed                                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     *Don’t
                       undertreat
Low emetic risk
Minimal emetic risk

                                       *Don’t
                                    underestimate
Platinum
Doxorubicin
Cytoxan
Dacarbazine
Aprepitant   Lorazepam        5-HT3 Antagoist




                                                Dexa
                               Dopamine
             PPI/H2-blocker
                               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
                                           *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
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                                Consider
    from                                  change
  different                            antiemetics
  drug class                            to higher
     PRN                                 level for
                                        next cycle


                Re-eval, adjust dose
                and or new drug
Anticipatory N/V
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 …
Non-Medical measures




•Eating small frequent meals
                                   Dietary
•Choice of food                       consult
  • Easy on stomach
•Eating food at room temperature
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
         +/- Dexa 4 mg qd
TBI:
   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
Port-a-Cath
Prophylactic antimicrobials
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)
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                           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
PCP Prophylaxis
          (Pneumocystis Jirovecii)


Drugs of choice:
TMP/SMX
 Preferred
 If allergic or intolerant:
   Desensitization or
   Dapsone, aerosolized Pentamidine, Atovaquone
G-CSF
10.0


         8.0


         6.0
W.B.C.




         4.0


         2.0



               Day 0
               (Chemo    Day 7           Day 21
               Starts)           Nadir
TREATMENT
Neutropenic Fever

                       Look for source of infection:
                       *Catheter sites
                       *Skin
                       *Lungs/Sinus
Temp > 38⁰ 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
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
                                                 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
NOT-RESPONDING:
                                      •FUO:
                                          •Stable:
                                               •Cont. same
                                               antibiotic
RESPONDING:
                                               •Consider
•Continue same
                                               antifungal (high
antibiotic until ANC >
                                               risk pts)
500 and rising
                                          •Unstable:
     •FUO:               *Daily F/U            •Cover
           •DC             *Eval               anaerobes, gram
           antibiotic
                         response              neg/positive,
     •Documented
     infection +/-
                          in 3-5 d             Candida
                                               •Consider G-CSF
     bactremia:
                                               •ID consult
           •Duration
                                      •Documented infection:
           of therapy
                                          •Antibiotic/pathogen
           varies
                                          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:
                         •Bloodstream infection with:
                             •Candida
                             •S. aureus
Recommended:                 •P. aeruginosa
•Septic phlebitis            •Corynbacterium jeikeium
•Tunnel infection            •Acinetobacter
•Port pocket infection       •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
     Severe mucositis                                      resistant Gram-
                                                             positive not
     Quinolone or Bactrim prophylaxis                       identified
       Recent studies: Vanco unnecessary if beta-lactam agent is used
Other agents for resistant Gram-positives




                     Linezolid (Zyvox)
*VRE
                     Quinupristin/Dalfopristin
*Vano not            (Synercid)
an option            Daptomycin (Cubicin)
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
Outpatient Therapy
        (Low Risk Neutropenic Fever)


                      • Daily monitoring at least
Drugs of choice:             for the first 3 days
• Outpt IV long-      • Return to clinic if:
  acting antibiotic      • Positive culture
• PO: Cipro 500mg        • New symptoms/signs
  q8h + Augmentin        • Persistent/recurrent
  or Clinda                 fever
                         • Oral intolerance
Management of chemotherapy complications

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Management of chemotherapy complications

  • 1.
  • 2. Management of Chemotherapy Complications Elshami M. Elamin, MD Medical Oncologist Central Care Cancer Center www.cccancer.com Wichita, KS - USA
  • 3.
  • 4. Introduction Chemotherapy: Affects the rapidly dividing cancer cells Also affects rapidly dividing normal cells Hair Mucous membranes Blood cells
  • 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
  • 9. Chemotherapy Side Effects Immediate Delayed within days Within weeks Late
  • 10. 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
  • 11. 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
  • 12. 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
  • 15. Within weeks Hair loss (Alopecia) Taxanes, Cisplatin, Doxo Peripheral neuropathy Pacltaxel, Oxalipatin, Cisplatin Dry skin or pigmentaion Nail changes Fluid retention Docetaxel
  • 16. 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
  • 17. Delayed Immediate A.E. A.E (days) Delayed Chemo A.E. Starts (Wks) Late A.E. ?
  • 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 … 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:
  • 20. TREATMENT OF SIDE EFFECTS AND COMPLICATIONS OF CANCER THERAPIES
  • 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?
  • 23. 23
  • 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 • Acute • Onset: minutes-hrs • Resolves: first 24 hrs It is easier to prevent N/V • Delayed than to treat it • Platinum, Cytoxan, Doxo • Onset: >24 hrs • May last for 7 days • Anticipatory • 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
  • 30. Categories of Emetogenic Chemotherapy High emetic risk Moderate emetic risk *Don’t undertreat Low emetic risk Minimal emetic risk *Don’t underestimate
  • 32. Aprepitant Lorazepam 5-HT3 Antagoist Dexa Dopamine PPI/H2-blocker antagonist
  • 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
  • 36. Watch for Dystonic reaction Prochlorperazine Metoclopramide Domperidone
  • 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
  • 38. Steroids Dexamethasone Always keep in mind its side effects *Hyerglycemia *HTN *Fluid retension *PU *Osteoporosis
  • 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 … It is not always doctors and nurses to do it … It is most of the time the patient to do it …
  • 48. Non-Medical measures •Eating small frequent meals Dietary •Choice of food consult • Easy on stomach •Eating food at room temperature
  • 49. Behavioral therapy Relaxation/systematic desensitization Hypnosis with guided imagery Music therapy Spiritual
  • 50. Radiation-Induced N/V 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
  • 52. PREVENTION 1. Neutropenic precaution 2. Prophylactic antimicrobials 3. G-CSF
  • 53. Neutropenic precaution Hand wash Gloves, Gowns, etc Accessing central venous lines: Written policy Training of medical staff Isolation
  • 54.
  • 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
  • 63. G-CSF
  • 64. 10.0 8.0 6.0 W.B.C. 4.0 2.0 Day 0 (Chemo Day 7 Day 21 Starts) Nadir
  • 66. Neutropenic Fever Look for source of infection: *Catheter sites *Skin *Lungs/Sinus Temp > 38⁰ 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: •FUO: •Stable: •Cont. same antibiotic RESPONDING: •Consider •Continue same antifungal (high antibiotic until ANC > risk pts) 500 and rising •Unstable: •FUO: *Daily F/U •Cover •DC *Eval anaerobes, gram antibiotic response neg/positive, •Documented infection +/- in 3-5 d Candida •Consider G-CSF bactremia: •ID consult •Duration •Documented infection: of therapy •Antibiotic/pathogen varies susceptibility •Consider G-CSF •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
  • 72. ?? Catheter Removal ?? Considered: •Bloodstream infection with: •Candida •S. aureus Recommended: •P. aeruginosa •Septic phlebitis •Corynbacterium jeikeium •Tunnel infection •Acinetobacter •Port pocket infection •Bacillus •Atypical mycobacteria •Yeasts or molds •VRE •Stenotrophomonas maltophilia
  • 73. 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 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) • Daily monitoring at least Drugs of choice: for the first 3 days • Outpt IV long- • Return to clinic if: acting antibiotic • Positive culture • PO: Cipro 500mg • New symptoms/signs q8h + Augmentin • Persistent/recurrent or Clinda fever • Oral intolerance