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Chemotherapy -– Questions With Complete Solutions
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Chemotherapy -– Questions With Complete Solutions
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Chemotherapy -– Questions With CompleteSolutions
Topoisomerases ✔️Ans -
Irinotecan ✔️Ans - Inhibits the re-ligation step of Topo I
Prodrug of SN-38 (relies on intact lactone ring for activity)
Use: GI cancers, esophagus to colon, including pancreas
DLT is diarrhea, which can be severe and life threatening! Relieved by use of
loperamide
Neutropenia is not cumulative and the drug can be given for extended periods
(>1 yr not uncommon)
Doxorubicin ✔️Ans - red devil
Cytotoxic
Topoisomerase inhibitor
BROAD spectrum anti cancer- especially breast cancer, lymphomas
Typical DLTs are stomatitis and myelosuppression
CARDIAC DAMAGE- can show up years after exposure, especially with existing
conditions, admin with radiation, or admin with other cardiotoxic drugs.
Mitigated by iron chelator
Can be partially mitigated by iron chelator
VESICANT- many require admin ONLY via central line
doXo= topoisomerase
Etoposide ✔️Ans - Cytotoxic
,Topoisomerase Inhibitor
Germ cell tumors, Lymphoma
***Can cause AML with shorter than typical latency for second malignancies
Topo= TOPO 2 inhibitor and 2ndary malignancies
Topoisomerase inhibitors ✔️Ans - irinotecan, doxorubicin and etoposide
Vinca alkaloids ✔️Ans - inhibit tubulin polymerization --> mitotic arrest
Neuropathy is DLT, as long-axon transport is sensitive to microtubule
disruption
Vincristine is not very myelosuppressive, and is therefore added to many
regimens
Vinblastine is extremely constipating
Taxanes ✔️Ans - Bind to inner surface of microtubule where GDP binds
the beta-subunit and STABILIZES the structure, PREVENTS
DEPOLYMERIZATION
Neuropathy is DLT
Broad spectrum activity
Refining delivery systems (some have allergy to industrial solvent its
dissolved in. Working to develop albumin bound paclitaxel= nab paclitaxel)
Carboplatin and paclitaxel is the most commonly used chemotherapy regimen
for solid tumors.
Anti-microtubule agents ✔️Ans - Vinca alkaloids (Vincristine), taxanes
(Paclitaxel), eribulin
, Paclitaxel ✔️Ans - Cytotoxic
Anti-mitotic, anti-tubulin
STABILIZES the structure, PREVENTS DEPOLYMERIZATION
small molecule
Epithelial malignancies, especially Breast and Ovarian
Ubiquitin proteasome system ✔️Ans - Ubiquitin binds to E1 --> E2 --> E3
brings them together
Recruits PEST sequences to promote ubiquitination
Once ubiquitinated --> threaded through molecular shredder (serine and
threonine proteasome)
Bortezomib ✔️Ans - Cytotoxic- Is technically a "slow-off" inhibitor, but
enzyme activity is essentially dead
Proteasome inhibitor- blocks 26S proteasome proteolytic activity
Inhibition lasts 24 hr after a single dose
Ubiquitination can be selectively toxic for cancer based on sensitivity to ER
stress
Fatigue, neuropathy and myelosuppression are dose-limiting
Has been extremely important in myeloma and other B-cell malignancies:
Multiple myeloma, mantle cell lympoma, Waldenstrom's
Think of the big damn bear- fatigue, neuropathy, myelosuppression
B= b cell malignancies
Z and b looks like 26- 26S proteasome inhibitor
Proteasome inhibitors ✔️Ans - bortezomib, carfilzomib, ixazomib
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