Transcript Complications of Chemotherapy

Chemotherapy – 2, 3 or 4 – week cycles.
- Only on day 1
- No further treatment until next cycle.
- Some regimens..... treatment are weekly
for 2 or 3 weeks with 1week off prior to next
cycle.
- Chemotherapy alone is curative in many
lymphomas, leukemia and germ cell tumors.
- Palliative chemotherapy – used to prolong
survival without affecting quality of life.
- Toxicities are widely variable &
potentially life – threatening.
- Most agents have narrow therapeutic
index & dosing is based on BSA (mg/m2).
Complications of Chemotherapy
• Discuss post-chemotherapy complications
and their management
• Chemotherapy can have wide-ranging
effects on patients
• Human body amazing at what it can
tolerate
What is chemotherapy?
• Treatment with drugs that kill cancer cells (or
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make them less active)
Interfering with tumour cells ability to grow and
proliferate
– Adjuvant chemotherapy ie localized breast cancer
– Induction chemotherapy ie AML
– Curative chemotherapy ie Diffuse Large B Cell
Lymphoma
– Palliative chemotherapy
Categories of Chemotherapy
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Antibiotic derived—anthracyclines, bleomycin
Plant Alkaloids—periwinkle plant--vincristine, paclitaxel
Alkylators—cylcophosphamide
Antimetabolites—interfere with synthesis of nucleic
acids-5FU, Methotrexate
Epipodophyllotoxins—inhibit topoisomerase 2--etoposide
Anti-hormonal—tamoxifen, coritcosteroids
TYROSINE KINASE INHIBITORS--GLEEVEC
MONOCLONAL ANTIBODIES—TARGETED therapy
Complications of Chemotherapy
• SHORT TERM
Fever
Nausea
Infusional reactions
Oral complications
Diarrhea
Anemia
Neuropathy
Alopecia
Rash, Extravasation
Emotional
Treatment of extravasation of selected
chemotherapeutic agents.
Drug
Dacarbazine
Daunorubicin
Doxorubicin
Etoposide
Compress
Hot
Cold
cold
Hot
Mechlorethamine
Mitomycin-C
Vinblastine
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Vincristine
Hot
Antidote
Isotonic thiosulfate IV and SC
DMSO applied topically to vein
DMSO applied topically to vein
Hyaluronidase (150 units/ml)
1-6 ml SC x 1
Isotonic thiosulfate IV and SC
Isotonic thiosulfate IV and SC
Hyaluronidase (150 units/ml)
1-6 ml SC x 1
Hyaluronidase (150 units/ml)
1-6 ml SC x 1
FEBRILE NEUTROPENIA
On Chemotherapy, 7 to 14 days post chemo
WBC nadir, NEUTROPHILS are 1st line of
DEFENCE
Temperature great than or equal to 38.3
degrees centigrade
Absolute Neutrophil count (ANC) less than
1.0
One of the few Oncologic EMERGENCIES
FEBRILE NEUTROPENIA
• History, Physical
• Focus on possible source of infection
• Respiratory tract, urine, skin, gi tract
• CBC, LFT,CR
• CXR
FEBRILE NEUTROPENIA
• Draw cultures from 2 different sites, urine
C/S
• 50% of cultures positive
– 65% positive cultures are gram positive
organisms
• Broad Spectrum antibiotics
• If well, hemodynamically stable
– CIPRO and AUGMENTIN PO and home
FEBRILE NEUTROPENIA
• IF UNWELL
• ADMIT WITH BROAD SPECTRUM IV
ANTIOBIOTICS IE TAZOBACTAM OR
IMIPENEM OR AMP AND GENT
• WITH FILGASTRIM SUPPORT( 300mcg sc
daily until anc >1.0), IV FLUIDS ETC.
FEBRILE NEUTROPENIA
• Usually fever lasts less than 48 hours
• If fever longer than 48 hrs, patient needs IV
antibiotics, consider antifungals
• Usually bacterial or viral infections but fungal
infections becoming more of an issue
• As WBC and ANC recover, patient usually
improves
NB special situation for Acute Leukemics, PICC
lines
FEBRILE NEUTROPENIA
• Clinical consideration and follow-up very
important, especially if patient discharged
home
NAUSEA
• Most chemotherapeutic agents cause
nausea
• Why?
1) systemically as drug makes it’s way to
nausea centre of brain
(chemotherapeutic trigger zone)
2) Sight and smell of drug
Neuronal pathways involved with
chemotherapy- and radiotherapy-induced
nausea and vomiting
Sensory input (pain, smell, sight)
Chemotherapy
Chemotherapy
Radiotherapy
Chemoreceptor
Trigger Zone
(area prostrema,
4th ventricle)
Stomach
Small intestine
Higher cortical
centres
Memory, fear, anticipation
Vomiting Centre
(medulla)
Vomiting Reflex
Labyrinths
Neuronal pathways
Factors which can
cause nausea & vomiting
NAUSEA
• Types of Nausea
– Anticipatory—conditioned reflex to sight and
smell of chemotherapy area
– Acute—within 24hrs and related to
chemotherapeutic agents
– Delayed—more than 24 hrs. post
chemotherapy--specific agents—cisplatin,
cyclophosphamide, adriamycin
NAUSEA
• Worst offenders:
– Cisplatin
– High dose cyclophosphamide
– Doxorubicin, eprirubicin, carboplatin also have
a high incidence of nausea
NAUSEA TREATMENT
Medications:
Prochlorperazine (stemetil)
Metoclopramide (maxeran)
Ondansetron (Zofran)—5HT3 antagonists
Dexamethasone
Lorazepam, Haloperidol
Aprepitant
Drug treatment of chemotherapy- and
radiotherapy-induced nausea and vomiting
Sensory input (pain, smell, sight)
Higher cortical
centres
Histamine antagonists
Muscarinic antagonists
Dopamine antagonists
Cannabinoids
Chemotherapy
Chemoreceptor
Trigger Zone
(area prostrema,
4th ventricle)
Memory, fear, anticipation
Benzodiazepines
Vomiting Centre
(medulla)
Vomiting Reflex
5HT3
antagonists
Sphincter modulators
Chemotherapy
Radiotherapy
Stomach
Small intestine
Labyrinths
Neuronal pathways
Factors which can
cause nausea & vomiting
Sites of action of drugs
NAUSEA TREATMENT
• Relaxation
• Varying foods, meals
Recommendations for antiemetic therapy
Phenothiazines
Prochlorperazine, 5-10 mg PO or IV q4-6h
(maximum IV dose, 40 mg/day)
Prochlorperazine, 25 mg PR q4-6h
Chlorpromazine, 10 mg PO q4-6h
Trimethobenzamide, 100 mg PO or IM q4-6h
Serotonin-receptor antagonists
Granisetron, 10 ug/kg IV or 1 mg PO q12h x
2 doses 15 mins before chemotherapy
Ondansetron, 8-32 mg IV x 15-30 mins
before or 24 mg PO or 8 mg PO tid
Dolasetron, 1.8 mg/kg IV or 100 mg PO 30
minutes before chemotherapy
Butyrophenone
Droperidol, 1-5 mg IV q4-6h
Metoclopramide, 2-3 mg/kg IV before
chemotherapy and q2h x 3 doses
Antihistamine
Diphenhydramine, 50 mg PO or IV q4-6h
Anxiolytic
Lorazepam, 1-2 mg PO or IV tid-qid
Glucocorticoid
Dexamethasone, 10-30 mg IV before
chemotherapy
INFUSIONAL REACTIONS
• Very common with new MONOCLONAL
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ANTIBODY agents ie RITUXIMAB
Infusion of these agents may take several hours
Fever, hypotension, asthmatic like reactions,
pain
Premedicate or treat with Dexamthasone,
diphenhydramine, paracetamol
May have to stop infusion temporarily
If serious, may have to discontinue agent
Oral Complications
• Occurs in approx 40% of patients
receiving chemotherapy
• Very common
• Team approach using nutritionist, nursing,
dentist, pain management team
• Oral hygiene important-soft tooth brushes,
floss?
• Source of bacteremia
Oral Complications
• loss of taste
– Affects appetite, nutrition
– Which in turn affects healing
– In this situation, we advise patients to think
of eating as a job
– Sometimes, oral complications require
nutrition supplements or alternatives
MUCOSITIS
• Chemotherapy is intended to injure rapidly
dividing cells such as the MUCOSA
• Presents with mouth sores, inflammation,
sometimes sloughing of mucosa anywhere
in the GASTROINTESTINAL TRACT, RESP
TRACT …
• Usually occurs in the mouth
MUCOSITIS
• SIMPLE ORAL MUCOSITIS TREATED WITH
MOUTH RINSE
– MAGIC MOUTHWASH
– SALT WATER GARGLES
– TOPICAL ANALGESIA ie Xylocaine viscous,
tantum
– Systemic analgesia
– NYSTATIN
MUCOSITIS
• Upper GI tract
– Heartburn
– Very common
• Antacid, Ranitidine, omeprazole
MUCOSITIS
• SEVERE MUCOSITIS
– GI TRACT
• DIARRHEA, SLOUGHING OF MUCOSA,
ESOPHAGITIS
• ADMISSION, TNA, BOWEL REST, OTHER
SUPPORTIVE MEASURES
• 5FU ONE OF THE MAIN CULPRITS
DIARRHEA
• VERY COMMON, approx 45%. USUALLY A
FEW DAYS AND SELF-LIMITING
DIARRHEA
• Risk factors
– Elderly
– Known colitis
– GI tumour
– 5FU, irinotecan
– Concomitant irradiation
DIARRHEA
• Infection—C difficle or other
• Laxatives, other medications (stool
softeners)
• Of course, usually the chemotherapy is the
culprit.
DIARRHEA
• Usually self-limiting
• Hydration—po, IV if more SERIOUS
• Diet—fluids, BRAT (Bananas, Rice, Apples,
Toast)
• Loperamide (immediately if on Irinotecan)
– 4mg followed by 2mg Q4H or until formed
stool. Up to 16 mg per day
– Usually rule out C difficle first
DIARRHEA
• If severe, Ocreotide (Sandostatin)
– Decreases fluid output from bowel
– 100mcg sc TID
– Growth hormone analogue-decreases all salivary
gland secretions
And Antibiotics may be considered espec if C difficle
positive
oral metronidazole or oral vancomycin
oral CIPRO
ANEMIA
• Bone marrow suppression from
chemotherapeutic agents
• Secondary to malignancy
• Anemia work-up
ANEMIA
• Chemotherapy induced anemia
• Erythropoietin, Darbepoetin alfa
– Stimulate marrow to produce RBC’s
– Used while on chemotherapy only
– Additional iron: po vs. iv
– Sc injection
ANEMIA
• Adverse effects of Erythropoietin
– Flu-like illness
– Rashes
– Diarrhea
– Headache
– Bone pain
– Liver, kidney
– Vascular event: FOLLOW HEMOGLOBIN
ANEMIA
• Dosage: Erythropoietin 40,000 units sc q
weekly
• Darbepoetin alfa : 150 mcg sc q weekly
to 7 days
NEUROPATHY
• Very common with vincristine, vinblastine,
cisplatin
• Usually temporary.
• Sometimes leads to dose alterations or
stopping of some drugs
NEUROPATHY
• Most commonly, we see numbness and
tingling in fingers and toes
• Can you do up your buttons?
• Is numbness becoming more proximal?
• May need to alter chemotherapeutic
agents or doses thereof
Emotional effects of chemotherapy
• Malignant diagnosis can be overwhelming
• The discussion of treatments and adverse
effects can also be overwhelming
• Anxiety, depression, fatigue related to
diagnosis and treatments
• LOTS of information regarding treatments
Emotional effects of chemotherapy
• “Gaining Control by giving up control”. Dr.
B. Rotella
• daily routine goes upside down
• Changing work routine…missing work for
weeks, months
• Income changes
Emotional effects of chemotherapy
• “The inability to forget is infinitely more
devastating than the inability to
remember”. Mark Twain
• Hard to forget some of the stressful times
one goes through
• Battle fatigue
Emotional effects of chemotherapy
• “It always seems impossible until it’s
done”. Nelson Mandela
• Getting through months of chemotherapy
is very, very difficult
• People are amazing though.
• The human condition is to battle
Emotional effects of chemotherapy
• “Things to do today: Exhale, Inhale,
Exhale”. Buddha
• Just surviving each day step by step
• Team approach: social worker, supportive
care coordinators, pastoral care, pharmacy
Complications of Chemotherapy
• Long term
– Cardiac
– Secondary Malignancies
– Fatigue
– Neuropathy
– Arthropathy
Cardiac Complications
• Adriamycin or other anthracyclines
• 450mg per m2 dose lifetime
• Strong treatment for breast cancer and
hematologic malignancies
• Affects myocardium longterm above
maximum dose
Secondary Malignancies
• Skin cancers
• Breast cancers
• Hematologic Malignancies
Fatigue
• Thorough history, physical exam and
ancillary tests
• Fatigue workshop
Arthropathy
• Post monoclonal antibodies
• Treated in usual fashion with NSAIDs,
prednisone
IMATINIB
• Oral “chemotherapy” for Chronic Myeloid
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Leukemia
Molecular model of chemotherapeutic
treatments, tyrosine kinase inhibitor
Philadelphia Chromosome produces abnormal
protein, BCR-ABL
Gleevec stops the signal of the BCR-ABL protein,
therefore halting Leukemogenesis
Fluid retention, diarrhea, nausea, fatigue, abdo
pain, muscle cramps, bone pain