Principles of Systemic Therapy

Question 1

indications for systemic therapy

Answer 1

• primary treatment
• adjuvant
• neoadjuvant
• palliation
• radio-sensitization

Question 2

local treatment modalities for cancer

Answer 2

surgery, radiotherapy

Question 3

systemic treatment modalities for cancer

Answer 3

conventional chemotherapy, targeted therapy, hormonal therapy, biological therapy

Question 4

gompertzian growth curve

Answer 4

growth fraction: % of cells that are in active cell division

growth rate: rate of growth of tumor cells, peaks before tumor is clinically detectable

Question 5

phases of gompertzian growth curve

Answer 5

• lag phase
• logarithmic phase
• plateau phase

Question 6

t/f chemo acts mainly on cells actively dividing or growing

Answer 6

true, best in cells in logarithmic phase

Question 7

at around ___ of maximum, growth becomes clinically detectable

Answer 7

75%, it takes only a few more divisions before it becomes lethal

Question 8

logarithmic kill model

Answer 8

• when chemo is administered, a constant fraction of tumor cells will die (3 log cell kill)
• 1 log regrowth in between sessions

Question 9

3 checkpoints for successful replication in the cell cycle

Answer 9

between g1 and s, end of g2, directly in m phase

Question 10

targets of cytotoxic drugs

Answer 10

antimetabolites, antibiotics, alkylating agents: s phase (get incorporated into dna leading to mutations and cell death)

vinca alkaloids, taxanes: m phase (attach to mircotubules during mitosis)

Question 11

what are alkylating agents

Answer 11

• cell cycle phase nonspecific (throughout cell cycle)

- busulfan, carmustine, cisplatin, cyclophosphamide, ifosfamide, melphalan

Question 12

what are antimetabolites

Answer 12

• interfere with purine and pyrimidine synthesis, active in s phase

Question 13

what are mitotic inhibitors

Answer 13

• inhibits mitosis by disaggregating microtubules (vinca alkyloids)
• disruptive polymerization (toxoids)
• active in m phase

Question 14

what are antibiotics

Answer 14

• bind to dna to generate free radicals that consequently cause dna damage
• affect key enzyme in dna synthesis

Question 15

principles of combination chemo

Answer 15

• prevention of resistant clones
• cyototoxic to both resting and dividing cells
• biochemical enhancement of effect
• rescue from adverse effects of treatment

Question 16

5fu and ___ have an enhancement effect, while ___ with leucovorin have a protective effect in primary cns lymphomas

Answer 16

5fu + leucovorin in colon cancer: enhancing

methotrexate + leucovorin: rescue from adverse effects

Question 17

other types of cytotoxic drugs

Answer 17

l asparagine depletion - l asapraginase
ribonucleotide reductase inhibitor - hydroxyurea
non-classic alkylating agents - procarbazine
topoisomerase II - etoposide and teniposide

Question 18

how can chemotherapy be given

Answer 18

iv, opd, during in-patient confinement, oral (ex. capecitabine)

Question 19

rationale for hormonal therapy

Answer 19

targeting tissues whose growth and function are under endogenous hormonal control (derived from tumor receptor status)

Question 20

t/f hormonal therapy is less toxic and more cytostatic than chemotherapy

Answer 20

true

Question 21

what is additive hormonal therapy

Answer 21

• corticosteroids, estrogen, progesterone, androgens
• hormones on top of endogenous hormones
• higher doses of steroids (dexamethasone and prednisone) are lymphotoxic
• use of corticosteroids for lymphoma

Question 22

what is ablative hormonal therapy

Answer 22

• antagonize effects of existing hormones
• breast = antiestrogen, prostate = antiandrogen, gonadotropin analogs
• surgeries: oophorectomy, ochiectomy

Question 23

estrogen signaling

Answer 23

read

Question 24

drugs for er (+) patients

Answer 24

• tamoxifen: blocks estrogen receptors by competitively binding to ER
• aromatase inhibitors: block conversion to active estrogen

Question 25

t/f hormonal therapy only works for er or pr positive patients

Answer 25

true

Question 26

how to detect er / pr positivity

Answer 26

immunohistochemistry (dark brown stains)

Question 27

t/f all biologic therapies are targeted therapies

Answer 27

false, interferons and interleukins are nonspecific

Question 28

marker for aggressive disease in breast cancer

Answer 28

her2 - dimerizes with other proteins of the same family - forms cascade of signals that lead to activation of transcription factors

Question 29

biological therapies against her2

Answer 29

trastuzumab, pertuzumab, t-dm, lapatinib

Question 30

what is trastuzumab

Answer 30

can attack her 2 at specific sites to block signaling

Question 31

what is pertuzumab

Answer 31

attacks her2 on different domains, prevents the dimerization to other her molecules

Question 32

challenges of targeted therapy

Answer 32

- requires careful selection - more cutaneous and gi side effects (due to egfr) - higher cost

Question 33

example of small molecule tyrosine kinase inhibitor

Answer 33

imatinib (gleevec) - competitively inhibits atp binding site of bcr-abl, pdgfr, and ckit (proteins in cml and gi stromal tumors) - oral

Question 34

effectiveness of imatinib

Answer 34

inhibition of bcr-abl resulted in - more complete responses - better progression free survivial rates - better overall survival

Question 35

t/f imatinib is more toxic than standard chemo

Answer 35

false, more severe side effects in chemo

Question 36

other kinase inhibitors

Answer 36

table 1

Question 37

what are monoconal antibodies

Answer 37

target cancer cell specific antigens to induce an immune response against the target cell (can be modified to deliver a toxin, radioisotope, or cytokine)

Question 38

examples of monoclonal antibodies

Answer 38

table 2

Question 39

what is egfr

Answer 39

- focus is crc | - activates kras-braf-mek pathway -> proliferation and cell survival

Question 40

moa of cetuximab and panitumumab

Answer 40

- inhibit egfr molecule from dimerizing and activating downstream pathways (control proliferation)

Question 41

biomarker for resistance to egfr drugs

Answer 41

kras mutation (does not need upstream activation)

Question 42

example of immune checkpoint blockade

Answer 42

- ctla4 and pdl1 | - pembrolizumab

Question 43

what is car t cell therapy

Answer 43

- collect patient's t cells - add cars on t cells - proliferate t cells - incoulate to patient

Question 44

vaccine approved for prostate cancer

Answer 44

- dendritic cell vaccine - sipuleucel t - harvest dendritic cells and train to present antigens - mature and return to patient (can better recodnize tumors)

Question 45

contraindications to systemic therapies

Answer 45

- infection - previous chemotherapy given <2 wks - major surgery <2 wks - leukopenia and thrombocytopenia - severely debilitated patients - 1st tri pregnancy - poor pt follow up - psycholocial problems

Question 46

recist criteria

Answer 46

- complete remission - partial remission (decrease by at lest 50%) - stable disease (regression <50% or no change in size) - progression (increase by at least 25%)

Question 47

performance status scale

Answer 47

ecog (0-5) and karnofsky (100-0)