Chp 44- principles of cancer therapy Flashcards
Define growth fraction
proportion of cells in a tumor that are actively involved in cell division
What happens to growth fraction as tumor size increases?
decreases as they enlarge because vascular supply and oxygen levels are decreased
Which drugs are phase nonspecific?
alkylating agents (cyclophosphamide, ifosfamide, melphalan), antitumor antibiotics, alkylating like agents (cisplatin, carboplatin)
Which drugs are G0 specific?
nitrosureas
Which drugs are G1 specific?
asparaginase, actinomycin D
Which drugs are S specific?
antimetabolites (mtx, 5FU), antifolates, antipyrimidines, antipurines
Which drugs are G2 specific?
bleomycin
When should drugs be used in combination?
- they are effective when used singly 2. have different MOA 3. at least additive
What is adjuvant therapy?
set course of combination chemo that is given in a high dose to patients who have no evidence of residual cancer after radiotherapy or surgery. Goal is to kill residual cells and cure.
What is neoadjuvant therapy?
aims to eradicate micrometastasis or reduce inoperable disease to prepare patients for surgery and/or radiotherapy
What is induction therapy?
combination high dose to cause remission
What is maintenance therapy?
long term low dose regimen to maintain remission
MOA of SERMS
competitive inhibitors of estrogen binding to ER in cytoplasm. SERM-ER complex binds to chromosomes but does not activate metabolism.
Uses of SERMs
prevent cancer recurrence, Important in breast cancers
AE of SERMS
increase risk of endometrial cancer and uterine sarcomas
What are aromatise inhibitors?
anastrozole, letrozole, used to suppress intratumor and plasma estrogen levels
Uses of AI
postmenopausal women with advanced breast cancer. Often used as adjuvant therapy or sequentially with tamoxifene
AE of AI
bone loss secondary to induced hypoestrogenic state
What are progestational agents and when are they used?
usely in tx of early stage endometrial cancer when surgery is no feasible, unsafe, or not desired. Useful in some pt with recurrent disease. MCly used agents are medroxyprogesterone and megestrol
How does ionizing radiation kill cells?
Via first order kinetic. produce free hydrogen ions and hydroxyl radicals which forms H2O2 with sufficient oxygen–> disrupts the structure of DNA
The basis of fractioned dosages comes from the 4 Rs of radiobiology?
repair or sublethal injury, repopulation, reoxygenation, redistribution in cell cyle
How is radiation measured?
rad (radiation absorbed dose). 1 gray=100 rad
What is teletherapy?
use of high energy beams. Spares skin and delivers less toxic radiation to bone. Used to shrink tumors before localized radiation.
What is brachytherapy?
Depends on inverse square law- dose of radiation at a given point is inversely proportional to the square of the distance from the radiation source. Uses incapsulated sources of radiation implanted directly into tissues (interstitial) or cavities (intracavitary).
What radioactive sources are used in intracavitary devices?
Low dose: cesium 137, high dose- iridium 192 or cobalt 60
What radioactive sources are used in interstitial impants?
iridium 192, iodine 125
Acute complications with radiation therapy
enteritis, acute cystitis, vulvitis, proctosigmoiditis, dedquamation, BM depression
Chronic complications with radiation therapy
small blood vessel obliteration, fibrosis, fistulas, rectal/sigmoid stenosis, hemorrhagic cystitis
Paclitaxel dlt, and AE
DLT: neutropenia, peripheral neuropathy. AE: alopecia, myalgias/arthralgias, GI tox, hypersensitivity rxn
Carboplatin dlt and ae
DLT: thrombocytopenia. AE: nephro, oto, GI toxicity, alopecia, hypersensitivity
Cisplatin dlt and ae
dlt- nephrotoxocity, ae- neuro and GI toxicity, hypersensitivity
bleomycin dlt and ae
dlt- pulm fibrosis ae- derm rxns
topotecan dlt and ae
dlt-neutropenia, ae- alopecia, gi tox
doxorubicin dlt and ae
myelosuppression ae- palmar-plantar erythrodysesthesia, gi tox ( stomatitis, n/v), cardiac
gemcitabine (antimetabolite) dlt and ae
dlt- neutropenia ae- hepato and nephro toxicity, HUS
etoposide dlt and ae
neutropenia ae- alopecia, gi tox, acute mi, acute leukemia
ifosfamide dlt and ae
dlt- hem cystitis, ae- nephro, gi tox, alopecia, mild leukopenia
mtx dlt and ae
dlt- myelosuppression of all cell lines ae-hepato, nephro, and derm toxicity
dactinomycin dlt and ae
myelosuppresion of all cell lines ae- gi tox, alopecia, extravasation necrosis
cyclophosphamide dlt and ae
myelosuppression ae- hem cystitis, alopecia, siadh
vincristine dlt and ae
myelosuppression ae- alopecia, gi tox, myalgias, peripheral neuropathy
Which drugs are used for ovarian cancer?
paclitaxel, carboplatin, topotecan, doxorubicin, gemcitabine
Which drugs are used for endometrial cancer?
dactinomycin. Adv-paclitaxel, carbopaltin
Which drugs are used for granulosa cell tumors?
paclitaxel, carboplatin
Which drugs are used for cervical cancer?
cisplatin
Which drugs are used for germ cell cancer?
cisplatin, bleomycin, etoposide
Which drugs are used for GTN?
etoposide, mtx, actD, cyclophos, vincristine
Which drugs are used for uterine sarcoma?
ifosfamide
Which drugs are used for molar pregnancy?
mtx
Trastuzumab moa
DNA derived monoclonal antibody to h EGF 2 protein (HER2)
Bevacizumab moa
VEGF
