Complications of Complications of ChemotherapyChemotherapy

• Discuss post-chemotherapy Discuss post-chemotherapy complications and their managementcomplications and their management

• Chemotherapy can have wide-Chemotherapy can have wide-ranging effects on patientsranging effects on patients

• Human body amazing at what it can Human body amazing at what it can toleratetolerate

What is chemotherapy?What is chemotherapy?

• Treatment with drugs that kill cancer cells Treatment with drugs that kill cancer cells (or make them less active)(or make them less active)

• Interfering with tumour cells ability to grow Interfering with tumour cells ability to grow and proliferateand proliferate– Adjuvant chemotherapy ie localized breast Adjuvant chemotherapy ie localized breast

cancercancer– Induction chemotherapy ie AMLInduction chemotherapy ie AML– Curative chemotherapy ie Diffuse Large B Cell Curative chemotherapy ie Diffuse Large B Cell

LymphomaLymphoma– Palliative chemotherapyPalliative chemotherapy

Categories of Categories of ChemotherapyChemotherapy

• Antibiotic derived—anthracyclines, bleomycinAntibiotic derived—anthracyclines, bleomycin• Plant Alkaloids—periwinkle plant--vincristine, paclitaxelPlant Alkaloids—periwinkle plant--vincristine, paclitaxel• Alkylators—cylcophosphamideAlkylators—cylcophosphamide• Antimetabolites—interfere with synthesis of nucleic Antimetabolites—interfere with synthesis of nucleic

acids-5FU, Methotrexateacids-5FU, Methotrexate• Epipodophyllotoxins—inhibit topoisomerase 2--Epipodophyllotoxins—inhibit topoisomerase 2--

etoposideetoposide• Anti-hormonal—tamoxifen, coritcosteroidsAnti-hormonal—tamoxifen, coritcosteroids• TYROSINE KINASE INHIBITORS--GLEEVECTYROSINE KINASE INHIBITORS--GLEEVEC• MONOCLONAL ANTIBODIES—TARGETED therapyMONOCLONAL ANTIBODIES—TARGETED therapy

Complications of Complications of ChemotherapyChemotherapy• SHORT TERMSHORT TERM

FeverFever NauseaNausea Infusional reactionsInfusional reactions Oral complicationsOral complications DiarrheaDiarrhea AnemiaAnemia NeuropathyNeuropathy AlopeciaAlopecia Rash, Extravasation Rash, Extravasation

EmotionalEmotional

FEBRILE NEUTROPENIAFEBRILE NEUTROPENIA

On Chemotherapy, 7 to 14 days post On Chemotherapy, 7 to 14 days post chemochemo

WBC nadir, NEUTROPHILS are 1WBC nadir, NEUTROPHILS are 1stst line of line of DEFENCEDEFENCE

Temperature great than or equal to 38.3 Temperature great than or equal to 38.3 degrees centigradedegrees centigrade

Absolute Neutrophil count (ANC) less than Absolute Neutrophil count (ANC) less than 1.01.0

One of the few Oncologic EMERGENCIESOne of the few Oncologic EMERGENCIES

FEBRILE NEUTROPENIAFEBRILE NEUTROPENIA

• History, PhysicalHistory, Physical

• Focus on possible source of infectionFocus on possible source of infection

• Respiratory tract, urine, skin, gi tractRespiratory tract, urine, skin, gi tract

• CBC, LFT,CRCBC, LFT,CR

• CXRCXR

FEBRILE NEUTROPENIAFEBRILE NEUTROPENIA

• Draw cultures from 2 different sites, Draw cultures from 2 different sites, urine C/Surine C/S

• 50% of cultures positive50% of cultures positive– 65% positive cultures are gram positive 65% positive cultures are gram positive

organismsorganisms

• Broad Spectrum antibioticsBroad Spectrum antibiotics• If well, hemodynamically stableIf well, hemodynamically stable

– CIPRO and CLAVULIN PO and homeCIPRO and CLAVULIN PO and home

FEBRILE NEUTROPENIAFEBRILE NEUTROPENIA

• IF UNWELLIF UNWELL

• ADMIT WITH BROAD SPECTRUM IV ADMIT WITH BROAD SPECTRUM IV ANTIOBIOTICS IE TAZOCIN OR ANTIOBIOTICS IE TAZOCIN OR IMIPENEM OR AMP AND GENTIMIPENEM OR AMP AND GENT

• WITH NEUPOGEN SUPPORT( 300mcg WITH NEUPOGEN SUPPORT( 300mcg sc daily until anc >1.0), IV FLUIDS sc daily until anc >1.0), IV FLUIDS ETC.ETC.

FEBRILE NEUTROPENIAFEBRILE NEUTROPENIA

• Usually fever lasts less than 48 hoursUsually fever lasts less than 48 hours• If fever longer than 48 hrs, patient needs If fever longer than 48 hrs, patient needs

IV antibiotics, consider antifungalsIV antibiotics, consider antifungals• Usually bacterial or viral infections but Usually bacterial or viral infections but

fungal infections becoming more of an fungal infections becoming more of an issueissue

• As WBC and ANC recover, patient usually As WBC and ANC recover, patient usually improvesimproves

NB special situation for Acute Leukemics, NB special situation for Acute Leukemics, PICC linesPICC lines

FEBRILE NEUTROPENIAFEBRILE NEUTROPENIA

• Clinical consideration and follow-up Clinical consideration and follow-up very important, especially if patient very important, especially if patient discharged homedischarged home

NAUSEANAUSEA

• Most chemotherapeutic agents Most chemotherapeutic agents cause nauseacause nausea

• Why? Why?

1)1) systemically as drug makes it’s way systemically as drug makes it’s way to nausea centre of brain to nausea centre of brain (chemotherapeutic trigger zone)(chemotherapeutic trigger zone)

2)2) Sight and smell of drugSight and smell of drug

Neuronal pathways involved with Neuronal pathways involved with chemotherapy- and radiotherapy-chemotherapy- and radiotherapy-induced nausea and vomitinginduced nausea and vomiting

Vomiting Centre (medulla)

StomachSmall intestine

Higher cortical centres

Chemoreceptor Trigger Zone

(area prostrema, 4th ventricle)

Memory, fear, anticipationSensory input (pain, smell, sight)

Labyrinths

Vomiting Reflex

Neuronal pathways

Factors which can cause nausea & vomiting

Chemotherapy

Chemotherapy

Radiotherapy

NAUSEANAUSEA

• Types of NauseaTypes of Nausea– Anticipatory—conditioned reflex to sight Anticipatory—conditioned reflex to sight

and smell of chemotherapy areaand smell of chemotherapy area– Acute—within 24hrs and related to Acute—within 24hrs and related to

chemotherapeutic agentschemotherapeutic agents– Delayed—more than 24 hrs. post Delayed—more than 24 hrs. post

chemotherapy--specific agents—chemotherapy--specific agents—cisplatin, cyclophosphamide, adriamycincisplatin, cyclophosphamide, adriamycin

NAUSEANAUSEA

• Worst offenders:Worst offenders:– CisplatinCisplatin– High dose cyclophosphamideHigh dose cyclophosphamide– Doxorubicin, eprirubicin, carboplatin Doxorubicin, eprirubicin, carboplatin

also have a high incidence of nauseaalso have a high incidence of nausea

NAUSEA TREATMENTNAUSEA TREATMENT

Medications:Medications:

Prochlorperazine (stemetil)Prochlorperazine (stemetil)

Metoclopramide (maxeran)Metoclopramide (maxeran)

Ondansetron (Zofran)—5HT3 antagonistsOndansetron (Zofran)—5HT3 antagonists

DexamethasoneDexamethasone

Lorazepam, HaloperidolLorazepam, Haloperidol

AprepitantAprepitant

Drug treatment of chemotherapy- and Drug treatment of chemotherapy- and radiotherapy-induced nausea and radiotherapy-induced nausea and vomitingvomiting

Vomiting Centre (medulla)

StomachSmall intestine

Higher cortical centres

Chemoreceptor Trigger Zone

(area prostrema, 4th ventricle)

Memory, fear, anticipationSensory input (pain, smell, sight)

Labyrinths

Vomiting Reflex

Neuronal pathways

Factors which can cause nausea & vomiting

Chemotherapy

Chemotherapy

Radiotherapy

Histamine antagonistsMuscarinic antagonistsDopamine antagonists

Cannabinoids

Sites of action of drugs

5HT3

antagonists

Sphincter modulators

Benzodiazepines

NAUSEA TREATMENTNAUSEA TREATMENT

• RelaxationRelaxation

• Varying foods, mealsVarying foods, meals

INFUSIONAL REACTIONSINFUSIONAL REACTIONS

• Very common with new MONOCLONAL Very common with new MONOCLONAL ANTIBODY agents ie RITUXIMABANTIBODY agents ie RITUXIMAB

• Infusion of these agents may take several Infusion of these agents may take several hourshours

• Fever, hypotension, asthmatic like Fever, hypotension, asthmatic like reactions, painreactions, pain

• Premedicate or treat with Dexamthasone, Premedicate or treat with Dexamthasone, Benadryl, TylenolBenadryl, Tylenol

• May have to stop infusion temporarilyMay have to stop infusion temporarily• If serious, may have to discontinue agentIf serious, may have to discontinue agent

Oral ComplicationsOral Complications

• Occurs in approx 40% of patients Occurs in approx 40% of patients receiving chemotherapyreceiving chemotherapy

• Very commonVery common• Team approach using nutritionist, Team approach using nutritionist,

nursing, dentist, pain management nursing, dentist, pain management teamteam

• Oral hygiene important-soft tooth Oral hygiene important-soft tooth brushes, floss?brushes, floss?

• Source of bacteremiaSource of bacteremia

Oral ComplicationsOral Complications

• loss of tasteloss of taste– Affects appetite, nutritionAffects appetite, nutrition– Which in turn affects healingWhich in turn affects healing– In this situation, we advise patients to In this situation, we advise patients to

think of eating as a jobthink of eating as a job– Sometimes, oral complications require Sometimes, oral complications require

nutrition supplements or alternativesnutrition supplements or alternatives

MUCOSITISMUCOSITIS

• Chemotherapy is intended to injure Chemotherapy is intended to injure rapidly dividing cells such as the rapidly dividing cells such as the MUCOSAMUCOSA

• Presents with mouth sores, inflammation, Presents with mouth sores, inflammation, sometimes sloughing of mucosa sometimes sloughing of mucosa anywhere in the GASTROINTESTINAL anywhere in the GASTROINTESTINAL TRACT, RESP TRACT …TRACT, RESP TRACT …

• Usually occurs in the mouthUsually occurs in the mouth

MUCOSITISMUCOSITIS

• SIMPLE ORAL MUCOSITIS TREATED SIMPLE ORAL MUCOSITIS TREATED WITH MOUTH RINSEWITH MOUTH RINSE– MAGIC MOUTHWASHMAGIC MOUTHWASH– SALT WATER GARGLESSALT WATER GARGLES– TOPICAL ANALGESIA ie Xylocaine TOPICAL ANALGESIA ie Xylocaine

viscous, tantumviscous, tantum– Systemic analgesiaSystemic analgesia– NYSTATINNYSTATIN

MUCOSITISMUCOSITIS

• Upper gi tractUpper gi tract– HeartburnHeartburn– Very commonVery common

•Antacid, Ranitidine, PantolocAntacid, Ranitidine, Pantoloc

MUCOSITISMUCOSITIS

• SEVERE MUCOSITISSEVERE MUCOSITIS– GI TRACTGI TRACT

•DIARRHEA, SLOUGHING OF MUCOSA, DIARRHEA, SLOUGHING OF MUCOSA, ESOPHAGITISESOPHAGITIS

•ADMISSION, TNA, BOWEL REST, OTHER ADMISSION, TNA, BOWEL REST, OTHER SUPPORTIVE MEASURESSUPPORTIVE MEASURES

•5FU ONE OF THE MAIN CULPRITS5FU ONE OF THE MAIN CULPRITS

DIARRHEADIARRHEA

• VERY COMMON, approx 45%. VERY COMMON, approx 45%. USUALLY A FEW DAYS AND SELF-USUALLY A FEW DAYS AND SELF-LIMITINGLIMITING

DIARRHEADIARRHEA

• Risk factorsRisk factors– ElderlyElderly– Known colitisKnown colitis– GI tumourGI tumour– 5FU, irinotecan5FU, irinotecan– Concomitant irradiationConcomitant irradiation

DIARRHEADIARRHEA

• Infection—CDIFF or otherInfection—CDIFF or other

• Laxatives, other medications (stool Laxatives, other medications (stool softeners)softeners)

• Of course, usually the chemotherapy Of course, usually the chemotherapy is the culprit.is the culprit.

DIARRHEADIARRHEA

• Usually self-limitingUsually self-limiting• Hydration—po, IV if more SERIOUSHydration—po, IV if more SERIOUS• Diet—fluids, BRAT (Bananas, Rice, Diet—fluids, BRAT (Bananas, Rice,

Apples, Toast)Apples, Toast)• Loperamide (immediately if on Loperamide (immediately if on

Irinotecan)Irinotecan)– 4mg followed by 2mg Q4H or until formed 4mg followed by 2mg Q4H or until formed

stool. Up to 16 mg per daystool. Up to 16 mg per day– Usually rule out CDIFF firstUsually rule out CDIFF first

DIARRHEADIARRHEA

• If severe, Ocreotide (Sandostatin)If severe, Ocreotide (Sandostatin)– Decreases fluid output from bowelDecreases fluid output from bowel– 100mcg sc TID100mcg sc TID– Growth hormone analogue-decreases all Growth hormone analogue-decreases all

salivary gland secretionssalivary gland secretions

And Antibiotics may be considered espec if CDIFF And Antibiotics may be considered espec if CDIFF positive positive

oral metronidazole or oral oral metronidazole or oral vancomycinvancomycin

oral CIPROoral CIPRO

ANEMIAANEMIA

• Bone marrow suppression from Bone marrow suppression from chemotherapeutic agentschemotherapeutic agents

• Secondary to malignancySecondary to malignancy

• Anemia work-upAnemia work-up

ANEMIAANEMIA

• Chemotherapy induced anemiaChemotherapy induced anemia

• Erythropoietin, AranespErythropoietin, Aranesp– Stimulate marrow to produce RBC’sStimulate marrow to produce RBC’s– Used while on chemotherapy onlyUsed while on chemotherapy only– Additional iron: po vs. ivAdditional iron: po vs. iv– Sc injectionSc injection

ANEMIAANEMIA

• Adverse effects of ErythropoietinAdverse effects of Erythropoietin– Flu-like illnessFlu-like illness– RashesRashes– DiarrheaDiarrhea– HeadacheHeadache– Bone painBone pain– Liver, kidneyLiver, kidney– Vascular event: FOLLOW HEMOGLOBINVascular event: FOLLOW HEMOGLOBIN

ANEMIAANEMIA

• Dosage: Eprex 40,000 units sc Dosage: Eprex 40,000 units sc qweekly Aranesp: 150mcg sc qweekly Aranesp: 150mcg sc qweeklyto 7 days)qweeklyto 7 days)

NEUROPATHYNEUROPATHY

• Very common with vincristine, Very common with vincristine, vinblastine, cisplatinvinblastine, cisplatin

• Usually temporary. Usually temporary.

• Sometimes leads to dose alterations Sometimes leads to dose alterations or stopping of some drugsor stopping of some drugs

NEUROPATHYNEUROPATHY

• Most commonly, we see numbness Most commonly, we see numbness and tingling in fingers and toesand tingling in fingers and toes

• Can you do up your buttons?Can you do up your buttons?

• Is numbness becoming more Is numbness becoming more proximal?proximal?

• May need to alter chemotherapeutic May need to alter chemotherapeutic agents or doses thereofagents or doses thereof

Emotional effects of Emotional effects of chemotherapychemotherapy

• Malignant diagnosis can be overwhelmingMalignant diagnosis can be overwhelming

• The discussion of treatments and adverse The discussion of treatments and adverse effects can also be overwhelmingeffects can also be overwhelming

• Anxiety, depression, fatigue related to Anxiety, depression, fatigue related to diagnosis and treatmentsdiagnosis and treatments

• LOTS of information regarding treatmentsLOTS of information regarding treatments

Emotional effects of Emotional effects of chemotherapychemotherapy

• ““Gaining Control by giving up Gaining Control by giving up control”. Dr. B. Rotellacontrol”. Dr. B. Rotella

• daily routine goes upside downdaily routine goes upside down

• Changing work routine…missing Changing work routine…missing work for weeks, monthswork for weeks, months

• Income changesIncome changes

Emotional effects of Emotional effects of chemotherapychemotherapy

• ““The inability to forget is infinitely The inability to forget is infinitely more devastating than the inability more devastating than the inability to remember”. Mark Twainto remember”. Mark Twain

• Hard to forget some of the stressful Hard to forget some of the stressful times one goes throughtimes one goes through

• Battle fatigueBattle fatigue

Emotional effects of Emotional effects of chemotherapychemotherapy

• ““It always seems impossible until it’s It always seems impossible until it’s done”. Nelson Mandeladone”. Nelson Mandela

• Getting through months of Getting through months of chemotherapy is very, very difficultchemotherapy is very, very difficult

• People are amazing though.People are amazing though.

• The human condition is to battleThe human condition is to battle

Emotional effects of Emotional effects of chemotherapychemotherapy

• ““Things to do today: Exhale, Inhale, Things to do today: Exhale, Inhale, Exhale”. BuddhaExhale”. Buddha

• Just surviving each day step by stepJust surviving each day step by step

• Team approach: social worker, Team approach: social worker, supportive care coordinators, supportive care coordinators, pastoral care, pharmacypastoral care, pharmacy

Complications of Complications of ChemotherapyChemotherapy

• LongtermLongterm– CardiacCardiac– Secondary MalignanciesSecondary Malignancies– FatigueFatigue– NeuropathyNeuropathy– ArthropathyArthropathy

Cardiac ComplicationsCardiac Complications

• Adriamycin or other anthracyclinesAdriamycin or other anthracyclines

• 450mg per m2 dose lifetime450mg per m2 dose lifetime

• Strong treatment for breast cancer Strong treatment for breast cancer and hematologic malignanciesand hematologic malignancies

• Affects myocardium longterm above Affects myocardium longterm above maximum dosemaximum dose

Secondary MalignanciesSecondary Malignancies

• Skin cancersSkin cancers

• Breast cancers Breast cancers

• Hematologic MalignanciesHematologic Malignancies

FatigueFatigue

• Thorough history, physical exam and Thorough history, physical exam and ancillary testsancillary tests

• Fatigue workshopFatigue workshop

ArthropathyArthropathy

• Post monoclonal antibodiesPost monoclonal antibodies

• Treated in usual fashion with NSAIDs, Treated in usual fashion with NSAIDs, prednisone prednisone

GLEEVECGLEEVEC

• Oral “chemotherapy” for Chronic Myeloid Oral “chemotherapy” for Chronic Myeloid LeukemiaLeukemia

• Molecular model of chemotherapeutic Molecular model of chemotherapeutic treatments, tyrosine kinase inhibitortreatments, tyrosine kinase inhibitor

• Philadelphia Chromosome produces Philadelphia Chromosome produces abnormal protein, BCR-ABLabnormal protein, BCR-ABL

• Gleevec stops the signal of the BCR-ABL Gleevec stops the signal of the BCR-ABL protein, therefore halting Leukemogenesisprotein, therefore halting Leukemogenesis

• Fluid retention, diarrhea, nausea, fatigue, Fluid retention, diarrhea, nausea, fatigue, abdo pain, muscle cramps, bone painabdo pain, muscle cramps, bone pain