Chemotherapy Basics For the Physical Therapist

Question 1

Second messenger pathways

Answer 1

Important for proliferation and differentiation

Intracellular and Extracellular

Question 2

Activation of oncogenes/inactivation of tumor supporessor genes

Answer 2

alters normal cell signaliing

Question 3

Surgery

Answer 3

remove known tumor masses

Question 4

radiation

Answer 4

kill rapidly dividing tumor cells including tumor cells in adjacent tissues

Question 5

chemotherapy

Answer 5

kill rapidly dividing tumor cells

Question 6

hormonal therapy

Answer 6

inhibit the growth and survival of hormone-dependent tumor cells

Question 7

targeted therapy

Answer 7

specifically inhibit processes required for tumor cell growth

Question 8

chemotherapy toxicity

Answer 8

“chemo brain”; mucositis; fatigue; nausea/vomiting; diarrhea; cystitis; sterility; 2nd cancers; neuropathy; alopecia; ototoxicity; pulmonary toxicity; cardiotoxicity; extravasations; organ failure; myelosuppression; skin reactions

Question 9

quantifying toxicity

Answer 9

numerical scale 1-5 (1=mild, 5=death)

Question 10

toxicity perspective

Answer 10

everyone gets some, no one gets all; grades 1-2 most common but 3-4 are likely; grade 5 uncommon

Question 11

grade 1-2 toxicity

Answer 11

accepted by oncology providers, dose reduction not warranted

Question 12

grade 3-4 toxicity

Answer 12

hold dose to permit recovery; reduce subsequent doses; prevention if possible

Question 13

myelosuppression

Answer 13

most common dose-limiting toxicity; onset depends on lifespan of blood cells

Question 14

neutropenia

Answer 14

low WBC count dur to radiation and chemo; precautions include washing hands and minimizing exposure to sick people and crowds

Question 15

thrombocytopenia

Answer 15

low platelet level; need to decrease fall risks (higher bleed risk); watch for increased bruising/petechiae, prolonged bleeding, concomitant meds

Question 16

anemia

Answer 16

signs: fatigue/cardiac symptoms; may be managed w/RBC transfusion, erythropoietic stimulating agents (chemo-induced anemia only)

Question 17

erythropoietic stimulating agents risks

Answer 17

Shortened survival and increase is tumor progression or recurrence
Increased risk of serious cardiovascular and thromboembolic events

Question 18

alopecia

Answer 18

scalp hair&raquo_space; other body hair; onset 1-2 weeks, maximal ~3 weeks; reversible (regrows in 2-3 months)

Question 19

alopecia risk

Answer 19

lowest: hormones, targeted agents; low/moderate: antimetabolites, heavy metals; high: classic alkylating agents; very high: anthracyclines and taxanes

Question 20

diarrhea info

Answer 20

mucosa has high cell turnover rate; direct and indirect toxic effects on mucosa; acute: within 24 hours of treatment, cholinergic symptoms; chronic: more than 24 hours after treatment, risk of dehydration

Question 21

nausea/vomiting types

Answer 21

acute, delayed, breakthrough, refractory, anticipatory

Question 22

blood clots

Answer 22

not as common but still important; watch for DVT/PE; cancer patients at higher risk

Question 23

chemotherapy agents associated with neurotoxicity

Answer 23

Drug Classes
Alkylating agents
Antimetabolites
Mitotic spindle agents
Proteasome inhibitors

Question 24

alkylating agents neurotoxicity (ifosfamide)

Answer 24

lethargy, dizziness, confusion, ataxia, coma

Question 25

platinum compounds

Answer 25

``` Cisplatin and Carboplatin Peripheral Neuropathy “Stocking and glove” Dysesthesias, parethesias, loss of proprioception Ototoxicity Vestibular toxicity Oxaliplatin Neuropathies Acute Cold-induced distal dysesthesia and/or paresthesia, hypoesthesia Occurs in hands, feet, perioral area, or throat. Persistent Cisplatin-like ```

Question 26

Antimetabolites

Answer 26

``` Mechanism of Action Act as structural analogues for DNA base pairs Inhibit critical enzymes in DNA synthesis Cytarabine Cerebellar syndrome Occurs with high doses Dysarthria, nystagmus, ataxia Gemcitabine No significant neurotoxicity Others Pulmonary toxicity Rare ```

Question 27

Antimetabolites - Methotrexate

Answer 27

Neurotoxicity Headache, N/V Motor paralysis, cranial nerve palsy Chronic demyelinating encephalopathy

Question 28

mitotic spindle agents

Answer 28

Mechanism: Promote and stabilize microtubule assembly and interfere with disassembly Peripheral neuropathy “Stocking and glove” Others Alopecia - total body

Question 29

Vinca Alkaloids Inhibit microtubule assembly Vincristine Vinblastine Vinorelbine

Answer 29

``` Neuropathy Sensory Paresthesias Motor Loss deep tendon reflexes Cranial Palsy Autonomic Constipation ```

Question 30

proteasome inhibitor

Answer 30

Bortezomib and Carfilzomib Indication: Multiple Myeloma & Non-Hodgkin’s lymphoma Peripheral neuropathy

Question 31

antitumor antibiotics

Answer 31

``` Mechanism of Action Intercalation into DNA Interact with topoisomerase Free radical productionAnthracyclines The “rubicins” Doxorubicin ``` Cardiotoxicity Acute – arrhythmias, pericarditis Chronic – Congestive cardiomyopathy

Question 32

molecularly targeted agents

Answer 32

Targeted therapy refers to treatment strategies directed against molecular pathways considered to be involved in neoplastic transformation Drug Classes Monoclonal antibodies Signal transduction inhibitors

Question 33

monoclonal antibodies

Answer 33

Trastuzumab, Pertuzumab, ado-trastuzumab Receptor: HER2 Indication: Breast cancer Reversible cardiac dysfunction – cardiomyopathy Bevacizumab Receptor: VEGF Indication: Colon and Lung cancer Rare heart failure, hypertension, Other - GI perforation

Question 34

signal transduction inhibitors

Answer 34

``` Tyrosine kinase inhibitors (TKIs) Sorafenib Receptors: RAF, KIT, VEGF and PDGF Indication: Renal Cell Cancer Other Hypertension, heart failure ``` ``` Sunitinib Receptors: FLT3, KIT, VEGF and PDGF Indication: Renal Cell Cancer & GIST Other Hypertension, heart failure ```

Question 35

rash

Answer 35

Monoclonal antibody Cetuximab Receptor: EGFR Indication: Colon cancer ``` Toxicity Acneform rash Other Pulmonary toxicity – rare but serious TKI Erlotinib Receptor: EGFR Indication: Lung and Pancreatic cancer ```

Question 36

hand-foot syndrome

Answer 36

Signs and symptoms Erythema and swelling Dysesthesia, blistering, desquamation ``` Agents Antimetabolites Fluorouracil (5-FU) Capecitabine TKIs Sunitinib, sorafenib Antitumor antibiotics Doxorubicin ```

Question 37

hormonal agents

Answer 37

Antiestrogens Tamoxifen, Toremifene, Fulvestrant thromboembolic events, hot flashes Aromatase inhibitors Anastrozole, Letrozole Hot flashes, joint pain Androgen Ablation Lutenizing hormone releasing hormone (LHRH) agonists Lueprolide, Gosrelin Hot Flashes, feminization, TUMOR FLARE

Question 38

"Chemo-Brain"

Answer 38

``` Found in 20-25% of patients Subtle shifts in cognitive function May be seen early or late in treatment May improve over 6 months – 2 years following chemotherapy Effects Difficulty concentrating Difficulty handling/performing multiple tasks Difficulty with memory ``` ``` Mechanism Unknown ? Which chemotherapy agents ? Genetic or hormonal factors Not a result of anemia, fatigue or depression ``` ``` Methods to help function more effectively ? work load Avoid multiple tasks Make lists Encourage more sleep ```