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/m 2 ).

Complications of Chemotherapy Discuss post-chemotherapy complications and their management Discuss post-chemotherapy complications and their management Chemotherapy can have wide-ranging effects on patients Chemotherapy can have wide-ranging effects on patients Human body amazing at what it can tolerate Human body amazing at what it can tolerate

What is chemotherapy? Treatment with drugs that kill cancer cells (or make them less active) Treatment with drugs that kill cancer cells (or make them less active) Interfering with tumour cells ability to grow and proliferate 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 Antibiotic derived—anthracyclines, bleomycin Antibiotic derived—anthracyclines, bleomycin Plant Alkaloids—periwinkle plant--vincristine, paclitaxel Plant Alkaloids—periwinkle plant--vincristine, paclitaxel Alkylators—cylcophosphamide Alkylators—cylcophosphamide Antimetabolites—interfere with synthesis of nucleic acids-5FU, Methotrexate Antimetabolites—interfere with synthesis of nucleic acids-5FU, Methotrexate Epipodophyllotoxins—inhibit topoisomerase 2--etoposide Epipodophyllotoxins—inhibit topoisomerase 2--etoposide Anti-hormonal—tamoxifen, coritcosteroids Anti-hormonal—tamoxifen, coritcosteroids TYROSINE KINASE INHIBITORS--GLEEVEC TYROSINE KINASE INHIBITORS--GLEEVEC MONOCLONAL ANTIBODIES—TARGETED therapy MONOCLONAL ANTIBODIES—TARGETED therapy

Complications of Chemotherapy SHORT TERM SHORT TERM Fever Fever Nausea Nausea Infusional reactions Infusional reactions Oral complications Oral complications Diarrhea Diarrhea Anemia Anemia Neuropathy Neuropathy Alopecia Alopecia Rash, Extravasation Rash, Extravasation Emotional Emotional

Treatment of extravasation of selected chemotherapeutic agents. Drug Compress Antidote Dacarbazine Hot Isotonic thiosulfate IV and SC Daunorubicin ColdDMSO applied topically to vein Doxorubicin coldDMSO applied topically to vein Etoposide HotHyaluronidase (150 units/ml) 1-6 ml SC x 1 Mechlorethamine ----Isotonic thiosulfate IV and SC Mitomycin-C ---- Isotonic thiosulfate IV and SC Vinblastine HotHyaluronidase (150 units/ml) 1-6 ml SC x 1 Vincristine HotHyaluronidase (150 units/ml) 1-6 ml SC x 1

FEBRILE NEUTROPENIA On Chemotherapy, 7 to 14 days post chemo WBC nadir, NEUTROPHILS are 1 st 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 History, Physical Focus on possible source of infection Focus on possible source of infection Respiratory tract, urine, skin, gi tract Respiratory tract, urine, skin, gi tract CBC, LFT,CR CBC, LFT,CR CXR CXR

FEBRILE NEUTROPENIA Draw cultures from 2 different sites, urine C/S Draw cultures from 2 different sites, urine C/S 50% of cultures positive 50% of cultures positive –65% positive cultures are gram positive organisms Broad Spectrum antibiotics Broad Spectrum antibiotics If well, hemodynamically stable If well, hemodynamically stable –CIPRO and AUGMENTIN PO and home

FEBRILE NEUTROPENIA IF UNWELL IF UNWELL ADMIT WITH BROAD SPECTRUM IV ANTIOBIOTICS IE TAZOBACTAM OR IMIPENEM OR AMP AND GENT 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. WITH FILGASTRIM SUPPORT( 300mcg sc daily until anc >1.0), IV FLUIDS ETC.

FEBRILE NEUTROPENIA Usually fever lasts less than 48 hours Usually fever lasts less than 48 hours If fever longer than 48 hrs, patient needs IV antibiotics, consider antifungals 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 Usually bacterial or viral infections but fungal infections becoming more of an issue As WBC and ANC recover, patient usually improves 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 Clinical consideration and follow-up very important, especially if patient discharged home

NAUSEA Most chemotherapeutic agents cause nausea Most chemotherapeutic agents cause nausea Why? 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

NAUSEA Types of 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: 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

NAUSEA TREATMENT Relaxation Relaxation Varying foods, meals 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 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, mg IV before chemotherapy

INFUSIONAL REACTIONS Very common with new MONOCLONAL ANTIBODY agents ie RITUXIMAB Very common with new MONOCLONAL ANTIBODY agents ie RITUXIMAB Infusion of these agents may take several hours Infusion of these agents may take several hours Fever, hypotension, asthmatic like reactions, pain Fever, hypotension, asthmatic like reactions, pain Premedicate or treat with Dexamthasone, diphenhydramine, paracetamol Premedicate or treat with Dexamthasone, diphenhydramine, paracetamol May have to stop infusion temporarily May have to stop infusion temporarily If serious, may have to discontinue agent If serious, may have to discontinue agent

Oral Complications Occurs in approx 40% of patients receiving chemotherapy Occurs in approx 40% of patients receiving chemotherapy Very common Very common Team approach using nutritionist, nursing, dentist, pain management team Team approach using nutritionist, nursing, dentist, pain management team Oral hygiene important-soft tooth brushes, floss? Oral hygiene important-soft tooth brushes, floss? Source of bacteremia Source of bacteremia

Oral Complications loss of taste 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 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 … Presents with mouth sores, inflammation, sometimes sloughing of mucosa anywhere in the GASTROINTESTINAL TRACT, RESP TRACT … Usually occurs in the mouth Usually occurs in the mouth

MUCOSITIS SIMPLE ORAL MUCOSITIS TREATED WITH MOUTH RINSE 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 Upper GI tract –Heartburn –Very common Antacid, Ranitidine, omeprazole Antacid, Ranitidine, omeprazole

MUCOSITIS SEVERE MUCOSITIS SEVERE MUCOSITIS –GI TRACT DIARRHEA, SLOUGHING OF MUCOSA, ESOPHAGITIS DIARRHEA, SLOUGHING OF MUCOSA, ESOPHAGITIS ADMISSION, TNA, BOWEL REST, OTHER SUPPORTIVE MEASURES ADMISSION, TNA, BOWEL REST, OTHER SUPPORTIVE MEASURES 5FU ONE OF THE MAIN CULPRITS 5FU ONE OF THE MAIN CULPRITS

DIARRHEA VERY COMMON, approx 45%. USUALLY A FEW DAYS AND SELF-LIMITING VERY COMMON, approx 45%. USUALLY A FEW DAYS AND SELF-LIMITING

DIARRHEA Risk factors Risk factors –Elderly –Known colitis –GI tumour –5FU, irinotecan –Concomitant irradiation

DIARRHEA Infection—C difficle or other Infection—C difficle or other Laxatives, other medications (stool softeners) Laxatives, other medications (stool softeners) Of course, usually the chemotherapy is the culprit. Of course, usually the chemotherapy is the culprit.

DIARRHEA Usually self-limiting Usually self-limiting Hydration—po, IV if more SERIOUS Hydration—po, IV if more SERIOUS Diet—fluids, BRAT (Bananas, Rice, Apples, Toast) Diet—fluids, BRAT (Bananas, Rice, Apples, Toast) Loperamide (immediately if on Irinotecan) 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) 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 Bone marrow suppression from chemotherapeutic agents Secondary to malignancy Secondary to malignancy Anemia work-up Anemia work-up

ANEMIA Chemotherapy induced anemia Chemotherapy induced anemia Erythropoietin, Darbepoetin alfa 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 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 Dosage: Erythropoietin 40,000 units sc q weekly Darbepoetin alfa : 150 mcg sc q weekly to 7 days Darbepoetin alfa : 150 mcg sc q weekly to 7 days

NEUROPATHY Very common with vincristine, vinblastine, cisplatin Very common with vincristine, vinblastine, cisplatin Usually temporary. Usually temporary. Sometimes leads to dose alterations or stopping of some drugs Sometimes leads to dose alterations or stopping of some drugs

NEUROPATHY Most commonly, we see numbness and tingling in fingers and toes Most commonly, we see numbness and tingling in fingers and toes Can you do up your buttons? Can you do up your buttons? Is numbness becoming more proximal? Is numbness becoming more proximal? May need to alter chemotherapeutic agents or doses thereof May need to alter chemotherapeutic agents or doses thereof

Emotional effects of chemotherapy Malignant diagnosis can be overwhelming Malignant diagnosis can be overwhelming The discussion of treatments and adverse effects can also be overwhelming The discussion of treatments and adverse effects can also be overwhelming Anxiety, depression, fatigue related to diagnosis and treatments Anxiety, depression, fatigue related to diagnosis and treatments LOTS of information regarding treatments LOTS of information regarding treatments

Emotional effects of chemotherapy “Gaining Control by giving up control”. Dr. B. Rotella “Gaining Control by giving up control”. Dr. B. Rotella daily routine goes upside down daily routine goes upside down Changing work routine…missing work for weeks, months Changing work routine…missing work for weeks, months Income changes Income changes

Emotional effects of chemotherapy “The inability to forget is infinitely more devastating than the inability to remember”. Mark Twain “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 Hard to forget some of the stressful times one goes through Battle fatigue Battle fatigue

Emotional effects of chemotherapy “It always seems impossible until it’s done”. Nelson Mandela “It always seems impossible until it’s done”. Nelson Mandela Getting through months of chemotherapy is very, very difficult Getting through months of chemotherapy is very, very difficult People are amazing though. People are amazing though. The human condition is to battle The human condition is to battle

Emotional effects of chemotherapy “Things to do today: Exhale, Inhale, Exhale”. Buddha “Things to do today: Exhale, Inhale, Exhale”. Buddha Just surviving each day step by step Just surviving each day step by step Team approach: social worker, supportive care coordinators, pastoral care, pharmacy Team approach: social worker, supportive care coordinators, pastoral care, pharmacy

Complications of Chemotherapy Long term Long term –Cardiac –Secondary Malignancies –Fatigue –Neuropathy –Arthropathy

Cardiac Complications Adriamycin or other anthracyclines Adriamycin or other anthracyclines 450mg per m2 dose lifetime 450mg per m2 dose lifetime Strong treatment for breast cancer and hematologic malignancies Strong treatment for breast cancer and hematologic malignancies Affects myocardium longterm above maximum dose Affects myocardium longterm above maximum dose

Secondary Malignancies Skin cancers Skin cancers Breast cancers Breast cancers Hematologic Malignancies Hematologic Malignancies

Fatigue Thorough history, physical exam and ancillary tests Thorough history, physical exam and ancillary tests Fatigue workshop Fatigue workshop

Arthropathy Post monoclonal antibodies Post monoclonal antibodies Treated in usual fashion with NSAIDs, prednisone Treated in usual fashion with NSAIDs, prednisone

IMATINIB Oral “chemotherapy” for Chronic Myeloid Leukemia Oral “chemotherapy” for Chronic Myeloid Leukemia Molecular model of chemotherapeutic treatments, tyrosine kinase inhibitor Molecular model of chemotherapeutic treatments, tyrosine kinase inhibitor Philadelphia Chromosome produces abnormal protein, BCR-ABL Philadelphia Chromosome produces abnormal protein, BCR-ABL Gleevec stops the signal of the BCR-ABL protein, therefore halting Leukemogenesis Gleevec stops the signal of the BCR-ABL protein, therefore halting Leukemogenesis Fluid retention, diarrhea, nausea, fatigue, abdo pain, muscle cramps, bone pain Fluid retention, diarrhea, nausea, fatigue, abdo pain, muscle cramps, bone pain