Principles of Systemic Therapy Flashcards
indications for systemic therapy
- primary treatment
- adjuvant
- neoadjuvant
- palliation
- radio-sensitization
local treatment modalities for cancer
surgery, radiotherapy
systemic treatment modalities for cancer
conventional chemotherapy, targeted therapy, hormonal therapy, biological therapy
gompertzian growth curve
growth fraction: % of cells that are in active cell division
growth rate: rate of growth of tumor cells, peaks before tumor is clinically detectable
phases of gompertzian growth curve
- lag phase
- logarithmic phase
- plateau phase
t/f chemo acts mainly on cells actively dividing or growing
true, best in cells in logarithmic phase
at around ___ of maximum, growth becomes clinically detectable
75%, it takes only a few more divisions before it becomes lethal
logarithmic kill model
- when chemo is administered, a constant fraction of tumor cells will die (3 log cell kill)
- 1 log regrowth in between sessions
3 checkpoints for successful replication in the cell cycle
between g1 and s, end of g2, directly in m phase
targets of cytotoxic drugs
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)
what are alkylating agents
- cell cycle phase nonspecific (throughout cell cycle)
- busulfan, carmustine, cisplatin, cyclophosphamide, ifosfamide, melphalan
what are antimetabolites
- interfere with purine and pyrimidine synthesis, active in s phase
what are mitotic inhibitors
- inhibits mitosis by disaggregating microtubules (vinca alkyloids)
- disruptive polymerization (toxoids)
- active in m phase
what are antibiotics
- bind to dna to generate free radicals that consequently cause dna damage
- affect key enzyme in dna synthesis
principles of combination chemo
- prevention of resistant clones
- cyototoxic to both resting and dividing cells
- biochemical enhancement of effect
- rescue from adverse effects of treatment
5fu and ___ have an enhancement effect, while ___ with leucovorin have a protective effect in primary cns lymphomas
5fu + leucovorin in colon cancer: enhancing
methotrexate + leucovorin: rescue from adverse effects
other types of cytotoxic drugs
l asparagine depletion - l asapraginase
ribonucleotide reductase inhibitor - hydroxyurea
non-classic alkylating agents - procarbazine
topoisomerase II - etoposide and teniposide
how can chemotherapy be given
iv, opd, during in-patient confinement, oral (ex. capecitabine)
rationale for hormonal therapy
targeting tissues whose growth and function are under endogenous hormonal control (derived from tumor receptor status)
t/f hormonal therapy is less toxic and more cytostatic than chemotherapy
true
what is additive hormonal therapy
- corticosteroids, estrogen, progesterone, androgens
- hormones on top of endogenous hormones
- higher doses of steroids (dexamethasone and prednisone) are lymphotoxic
- use of corticosteroids for lymphoma
what is ablative hormonal therapy
- antagonize effects of existing hormones
- breast = antiestrogen, prostate = antiandrogen, gonadotropin analogs
- surgeries: oophorectomy, ochiectomy
estrogen signaling
read
drugs for er (+) patients
- tamoxifen: blocks estrogen receptors by competitively binding to ER
- aromatase inhibitors: block conversion to active estrogen
t/f hormonal therapy only works for er or pr positive patients
true
how to detect er / pr positivity
immunohistochemistry (dark brown stains)
t/f all biologic therapies are targeted therapies
false, interferons and interleukins are nonspecific
marker for aggressive disease in breast cancer
her2
- dimerizes with other proteins of the same family
- forms cascade of signals that lead to activation of transcription factors
biological therapies against her2
trastuzumab, pertuzumab, t-dm, lapatinib
what is trastuzumab
can attack her 2 at specific sites to block signaling
what is pertuzumab
attacks her2 on different domains, prevents the dimerization to other her molecules
challenges of targeted therapy
- requires careful selection
- more cutaneous and gi side effects (due to egfr)
- higher cost
example of small molecule tyrosine kinase inhibitor
imatinib (gleevec)
- competitively inhibits atp binding site of bcr-abl, pdgfr, and ckit (proteins in cml and gi stromal tumors)
- oral
effectiveness of imatinib
inhibition of bcr-abl resulted in
- more complete responses
- better progression free survivial rates
- better overall survival
t/f imatinib is more toxic than standard chemo
false, more severe side effects in chemo
other kinase inhibitors
table 1
what are monoconal antibodies
target cancer cell specific antigens to induce an immune response against the target cell
(can be modified to deliver a toxin, radioisotope, or cytokine)
examples of monoclonal antibodies
table 2
what is egfr
- focus is crc
- activates kras-braf-mek pathway -> proliferation and cell survival
moa of cetuximab and panitumumab
- inhibit egfr molecule from dimerizing and activating downstream pathways (control proliferation)
biomarker for resistance to egfr drugs
kras mutation (does not need upstream activation)
example of immune checkpoint blockade
- ctla4 and pdl1
- pembrolizumab
what is car t cell therapy
- collect patient’s t cells
- add cars on t cells
- proliferate t cells
- incoulate to patient
vaccine approved for prostate cancer
- dendritic cell vaccine
- sipuleucel t
- harvest dendritic cells and train to present antigens
- mature and return to patient (can better recodnize tumors)
contraindications to systemic therapies
- 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
recist criteria
- complete remission
- partial remission (decrease by at lest 50%)
- stable disease (regression <50% or no change in size)
- progression (increase by at least 25%)
performance status scale
ecog (0-5) and karnofsky (100-0)
