Cancer

Question 1

Cancer cell characteristics

Answer 1

• uncontrolled cellular growth
• ability to invade adjacent structures and/or travel to distant areas (metastases)
• incapable of physiologic functions of the mature tissue of origin
• altered proteins, enzyme systems, membrane characteristics, and cytogenetics

Question 2

What is TNM?

Answer 2

Tumor-size
Nodal-spread –> local/systemic
Metastasis –> M0-no and M1-yes

Question 3

What is adjuvant chemotherapy?

Answer 3

given after surgery to reduce risk of local and systemic recurrence

Question 4

What is neoadjuvant chemotherapy?

Answer 4

given prior to surgical intervention to reduce tumor size or to remove micrometastases

Question 5

What is cytotoxic chemotherapy?

Answer 5

• 1st chemo
• traditional
• toxic to all cells but more specific for rapidly dividing cells like the GI tract, hair follicles, bone marrow

Question 6

What is double time?

Answer 6

time needed for a tumor cell production to double in size

Question 7

What gompertzian growth?

Answer 7

early growth is exponential but as tumor gets bigger, growth slows due to decreased nutrients/blood supply

Question 8

what is log-kill hypothesis?

Answer 8

a given dose of chemotherapy kills the same fraction of tumor cells regardless of the size of the tumor at the time of treatment
-better efficacy in smaller tumors

Question 9

What are the principles of cytotoxic chemotherapy?

Answer 9

combo chemo/regimen

• good single-agent activity against tumor
• different moa
• different onsets of toxicities
• max cell kill within toxicity limits
• different moa to target a cancer cell in a diff way
• decrease drug resistance

Question 10

how are cytotoxic chemotherapy dosed?

Answer 10

dosed usually based on body surface area (BSA) and administered in cycles of 14, 21, or 28 days

Question 11

What is dose density?

Answer 11

want to give the same amount of chemo at schedule time (same dose every 1 weeks)

Question 12

what is dose intensity?

Answer 12

compressed dosing time to as short as possible

Question 13

what are alkylating agents?

Answer 13

• prevents cell division by cross-linking DNA strands and decreasing DNA synthesis
• cell cycle non-specifc
• myelosuppression is generally the dose-limiting toxicity

Question 14

what are the types of cross-linking prevention?

Answer 14

• monoalkylation
• intercalation
• crosslinked interstrand
• crosslinked intrastrand

Question 15

What are some alkylating agents?

Answer 15

cyclophosphamide, ifosfamide, cisplatin, carboplatin, oxaplatin

Question 16

What common toxicities in alkylating agents?

Answer 16

• n/v (acute/delayed)
• myelosuppresion
• alopecia
• sterility/infertility
• secondary malignancies

Question 17

Cyclophosphamide/ifosfamide toxicities

Answer 17

need to be given together to prevent-
hemorrhagic cystitis (primarily ifosfamide) due to acrolein metabolite
-give mesna

Question 18

Cisplatin toxicities

Answer 18

causes the most toxicities

• nephrotoxicity
• severe n/v (acute within 24 hrs and delayed up to 7 days later)
• ototoxicity (mostly children)

Question 19

Oxaliplatin toxicity

Answer 19

neuropathies (exacerbated by cold temperatures)

Question 20

Antimetabolites

Answer 20

• analogs of purines and pyrimidine compete with normal metabolites or falsely insert themselves for a metabolite normally incorporated into DNA or RNA
• most commonly active in Sphase

Question 21

Antimetaboltes drugs

Answer 21

methotrexate, capecitabine, fluorouracil, cytarabine

*anti-folate

Question 22

Antimetabolites toxicities

Answer 22

common: myelosuppression, mucositis, mild n/v, diarrhea

Question 23

Methotrexate (MTX) toxicities

Answer 23

• renal toxicities
• Leucovorin rescue for high doses after 24 hrs to restart folic acid cycle
• Cisplatin and MTX = never because of synergy effect and kill kidneys

Question 24

Cytarabine toxicities

Answer 24

high dose therapy: nervous system (cerebellar) toxicities of fine motor skills
-ocular irritation: steroid eye drops

Question 25

Fluorouracil toxicities

Answer 25

leucovorin- rescue dose only for MTX

Question 26

Capecitabine toxicity

Answer 26

hand-foot syndrome

Question 27

What are natural products of anti-neoplastic therapy?

Answer 27

- antitumor antibiotics - plant alkaloids (vinca alkaloids, taxanes, topoisomerase 1 and 2) - marine-based products - enzymes

Question 28

Antitumor antibiotics drugs

Answer 28

anthracyclines- block DNA and RNA transcription -Doxorubicin mitomycin-crosslinks DNA (not used anymore) dactinomycin-blocks RNA synthesis (kids only) bleomycin-inhibits DNA synthesis (one cell-cycle specific agent)

Question 29

Antitumor antibiotics toxicities

Answer 29

n/v, alopecia, stomatitis, myelosuppression

Question 30

Bleomycin toxicities

Answer 30

antitumor antibiotics | -lung toxicity--> pulmonary fibrosis, interstitial pneumonitis

Question 31

Anthracyclines toxicities

Answer 31

antitumor antibiotics - Doxorubicin | -cardiotoxicity - specifically for CHF

Question 32

Antitumor antibiotics- myocardiotoxicity

Answer 32

dose-dependent - production of toxic free radicals, membrane lipid peroxidation leading to irreversible damage and replacement by fibrous tissue - risk factor: cumulative dose, patient age, concomitant chemo with known cardiotoxicity, rad therapy - early tox: HF can develop within 3 months following completion - late tox: sx may appear one decade later - give dexrazoxane--> edta like chelating agent, binds intracellular iron released following lipid peroxidation

Question 33

Natural product - microtubules agents

Answer 33

- works at m phase - synthetic and semi-synthetic - different mechanism of actions--> prevent microtubule assembly(vinca alkaloids) or prevent microtubule disassembly (taxanes)

Question 34

Taxanes toxicities

Answer 34

plant alkaloids-microtubule toxicities - Docetaxel -neuropathies, peripheral edema, hypersensitivity reaction (to solvent for drug, not actual drug) - Paclitaxel- neuropathies, hypersensitivity rxn -premedicate with H1 and H2 blockers and steroid 30 mins prior

Question 35

Vinca Alkaloids toxicities

Answer 35

-all start with Vin -Vincristine- neuropathies, severe constipation(anal tears) Do not five intrathecal-->death -Vinblastine -Vinorelbine-myelosuppression

Question 36

Natural Products and Toxicities

Answer 36

Topoisomerase inhibitor 1+2- inhibit DNA repair mechanism Irinotecan-diarrhea (I ran to the can) - due to cholinergic rxn - delayed-loperamide (16dosemax/day) and atropine Etoposide-2nd cancers Asparaginase- specifically for leukemias, hypersensitivity rxn, hyperglycemia, pancreatitis, coagulopathies (ecoli derived)

Question 37

Natural products | Marine-based products

Answer 37

Eribulin- sea sponge -microtubule-like agents toxicities- fatigue, peripheral neuropathym, CINV-chemo induced n/v Trabectedin-sea squirt - mechanism-somwhat like alkylating agent - toxicities- fatigue, hand-foot syndrome, CINV, hepatic damage

Question 38

Hormonal Tx

Answer 38

- blocks production of hormones or hormone receptors in the body (breast and prostate - anti-estrogens - anti-androgens - luteinizing hormones-releasing hormones (LHRH) analogs

Question 39

SERM

Answer 39

Hormonal therapy Tamaoxifen (antagonist) -used in pre and postmenopausal women -benefits:↓ odd of recurrence 37% and ↓15 yrs survival by 31% -ADR: ↑ cataracts, endomentrial cancer, VTE, *CYP2D6 active metabolite, DDI with SSRI

Question 40

Aromatase Inhibitor

Answer 40

Hormonal therapy Letrozolem anastrozole, exemestane -postmeno preferred, premeno when combo with ovarian suppression -benefits: post-aromatase inhibitor for 5 yrs ↓ recurrence pre-varies add with OS -ADR: osteoporosis, fractures, arthralgias

Question 41

Hormonal Therapy for Prostate Cancer

Answer 41

LHRH agonist: Leuprolide, goserelin, triptorelin 1st line therapy, inhibits negative feedback from releasing LH and FSH to stop stimulation of testes to produce testosterone -tumor flare LHRH antagonist Degarelix -directly inhibits pituitary from releasing LH and FSK -2nd line therapy Antiandrogens Abiraterone, Bicalutamide, flutamide, nilutamide, enzalutamide, apalutamide

Question 42

ADR for hormonal therapy

Answer 42

- decrease hormone production --> hot flashes for men and women - little protective effect on heart --> lipids will increase and increase risk of cardiac events when they'll older - develop DB?

Question 43

Targeted Agents

Answer 43

identifies certain features of a cancer cell that makes it different from the normal cell - prevent tumor cells from entering cell cycle or target signals that trigger cancer growth, mets, and immorality - monoclonal antibodies-antibodies that match an antigen on the cancer cell surface - molecularly targeted therapies-blocks signaling inside the cell

Question 44

ADR Targeted Agents

Answer 44

- hair depigmentation (stripes) - dysphonia - hypothyroidism - hypersenstivity rxn with all monoclonal antibodies - QTc prolongation - neuropathy - fatigue

Question 45

Targeted Agent Drugs

Answer 45

monoclonal antibodies- end in umab | small molecule targeted therapies - end in -nib

Question 46

What are target types?

Answer 46

VEGF(R) inhibitor- vascular endothelial growth factor stops cancer angiogenesis -causes hypertension (caution in DB), proteinuria, bleeding and impaired wound healing (stop pre/post surgery) -HTN is a sign of efficacy -ben, sun, pazo, regor EGFR inhibitors- epidermal growth factor receptor - erlo, gef, alec, cet, panitu - acneiform rash - looks like acne.dry rash - treat with tetracycline, topical abx, and moisturizer - rash sign of efficacy mTOR inhibitors0 mammalian target of rapamycin - ever, siro, tem - hyperglycemia, dyslipidemia, muscosal senstitivty, mouth ulcers - DDI with 3A4 BCR-ABL mutation inhibition- translocation of chromosome (give in small doses) - CYP 3A4 substrate except pona - ima 3A4 inhibitor and peripheral edema - ima, das, nilo, pona, bosu - low levels of constant nausea

Question 47

Specific Targets

Answer 47

CD20- ritx, ofatu, obin (DLBCL targets b cells) -infusion rxn, myelosuppression HER2 inhibition - traz. pert-- cardiotoxicity - lapa= hand-foot syndrome, ddi with strong 3A4 inducer/inhibitor

Question 48

Target agent toxicities

Answer 48

monoclonal antibodies -potential hypersensitivity rxn based on mAb origin QT prolongation -nilo, pazo, pona Brentuximab -neuropathy Vemurafenib -colitis Bortezomib -neuropathies fatigue everyday!, hair thinning, low grade n/v/myelosuppression -hypothyroidism (sun, pazo, rego)