SET3 Flashcards
A patient with hepatic mets is slated to receive docetaxel as part of the therapy, what is a potential problem here?
Docetaxel (and other taxanes) are hepatically metabolized, so patients with bilirubin >7 due to infiltrative dz should have this held
What is the MOA of Fludarabine? AE?
Purine analog that inhibits DNA synthesis by interfering with DNA polymerase and Ribonucleotide reductase; lymphopenia and AIHA
What drugs are safe to give to pregnant woman with breast CA? When can you do it?
Cyclophosphamide and Doxorubicin in 2nd and 3rd trimester; Trastuzumab and Paclitaxel are not safe to give; trastuzumab can cause oligohydramnios
What drug should be given to HBV+ patients who are slated to begin Rituximab i.e. R-CHOP for DLBCL
Entacavir > Lamivudine
What drugs have been shown to be beneficial for prevention of chemotherapy-related neuropathy? Which for the treatment?
None shown to be beneficial in preventing but Duloxetine can treat chemo related peripheral neuropathy
If a person is to develop MDS or AML after exposure to Etoposide, when will it likely happen? What will be the abnormality?
2-3 years; 11q23 mutation affecting the MLL gene (Mixed Lineage Leukemia)
Where is CD52 found?
Mature lymphocytes; Alemtuzumab is anti-CD52 used in CLL but note that CD52 is on BOTH B and T lymphocytes so causes impaired cell-mediated immunity
What prophylaxis do patients receiving purine analogs (Fludarabine) or Alemtuzumab for CLL need?
Bactrim ppx because these drugs will cause lymphopenia not only of the B cells but also of T cells
What is the difference between paclitaxel and Nab-Paclitaxel?
Nab = nanoparticle albumin bound; it is a solvent free paclitaxel formulation that decreases solvent related reactions
Name 4 Microtubule destabilizing agents that prevent polymerization
Vinca Alkaloids (Vinblastine, Vincristine, Vinorelbine) and Eribulin (not vinca alkaloid)
What are the main adverse effects of TDM-1 (Kadcycla)?
Thrombocytopenia, increased LFT, cardiotoxicity (contains trastuzumab)
Why is subcortical edema commonly seen in PRES? Name 3 drugs that can cause it
The HTN and vasospasm lead to breakdown of BBB and hence edema leading to cortical blindness; Tacrolimus, Cyclosporine, and Bevacizumab
What is the MOA of taxanes? Name the 2 MC
They promote tubulin assembly into microtubles and inhibit their DEPOLYMERIZATION; paclitaxel and docetaxel
How long can hypomethylating agents such as azacitadine and decitabine take to show response?
Sometimes as long as 4-6 cycles; therefore would not consider the dz refractory after only a couple of cycles
What chemo drugs are vesicants? Which are irritants?
Vesicants = anthracyclines, vinca alkaloids; Irritants = taxanes and platinum analogs
Name 3 Vinca Alkaloids and their MOA
Vincristine, Vinblastine, Vinorelbine; Microtubule destabilizing agents that prevent polymerization
What are some adverse effects of Bevacizumab?
HTN is MC and basically is expected/on-target; organ perforation, PRES, nephrotic syndrome, DVTs, and poor wound healing
A patient with Her2+ breast CA that has received Cyclophosphamide + doxorubicin with weekly paclitaxel and is now on Trastuzumab and progressing could receive what?
Kadcycla (TDM-1) which is Trastuzumab + linker protein + maytansine and used in pt who have failed trastuzumab
True or False: An elderly pt with AML who is on decitabine has completed 2 cycles, her CBC is unchanged from baseline– she has refractory dz
False; hypomethylating agents such as 5-Azacitidine and Decitabine can take up to 4-6 cycles to show response
How long after allogeneic stem cell transplant should a person stay on posaconazole? How long should they have CMV monitored?
75 days; monitor for 6 months
What are three HDAC inhbitors that can be used in Cutaneous T cell Lymphomas that have failed other therapy?
Romidepsin, Vorinostat, Rocilinostat
MOA of Sunitinib
Affects multiple TKIs including VEGF and is used in metastatic RCC, often causes HTN which predicts for good outcome
What is the difference between Bevacizumab and ziv-aflibercept?
Bevacizumab targets VEGF-A; ziv-aflibercept targets VEGF-Trap
What is the best antifungal for neutropenic ppx? How is it metabolized?
Posaconazole; hepatically
What is the most concerning AE of Enzalutamide (i.e. for prostate CA)?
It can cause seizures, if this happens need to permanently stop the drug
In AlloHSCT what are the MC infxns before engraftment occurs? From day engraftment to day 100?
Initially it is bacterial, viral, and fungal; from engraftment to day 100 CMV and fungal, so will be on posaconazole and monitor CMV until 6 months out from xplant
What is the most serious AE of G-CSF?
Splenic rupture; more commonly bone pain
What is an on-target side effect of drugs affecting the vascular endothelial growth factor pathway?
HTN i.e. Bevacizumab and Sunitinib
What drug is a recombinant carboxypeptidase that converts MTX to glutamate?
Glucarpidase; used when high MTX levels and renal insufficiency
A patient is slated to receive HD MTX for CNS ppx and is noted to have a moderate pulmonary effusion, next step?
Effusion needs to be drained as the MTX will sequester in the effusion and caused prolonged toxicity
What is the MOA of Obinutuzumab?
It is a type II glycoengineered antibody that targets CD20
What if you have given HD MTX to a person for CNS ppx and they happen to develop AKI for other reason and MTX level is elevated despite alkalinizing urine?
You can give Glucarpidase which is a recombinant carboxypeptide that converts MTX into glutamate
What is another name for BCNU? Adverse effect?
Carmustine; delayed myelosuppresion i.e. up to 6w out from administration; 2nd line for GBM as first is surgery and temozolomide
What is the other name for Kadcycla? What are the 3 components of it?
TDM-1; Trastuzumab + Linker Protein + Maytansine; Maytansine is inhibitor of tubulin polymerization; used for Her2+ metastatic Breast CA that progressed on trastuzumab and taxane
What is the most common AE of aromatase inhibitors?
Arthralgias; also promotes osteoporosis, causes hot flashes
For whom is Alemtuzumab approved? Explain why it can predispose to infxn?
CLL patients who have failed aklylating agents or fludarabine; CD52 expressed on both mature B and T lymphocytes so destroys both, loss of T cell = more infxn, monitor CMV q2 month
What does Nab-Paclitaxel stand for? What is the brand name?
Nanoparticle Albumin Bound-Paclitaxel; Abraxane
True or False: a history of alcohol use predicts for a patient to have a lot of adverse effects from chemo
False; in fact their CYP enzymes are on overdrive from the chronic EtOH consumption so they deal with chemo better
Kehr sign may be seen when giving what supportive agent during chemo?
G-CSF (Neulasta, Neupogen); Kehr sign is L sided shoulder pain from splenic rupture; splenic rupture is a rare AE of G-CSF
The CLL11 trial showed that which of the following is best: Chlorambucil alone, Chlorambucil + Obinutuzumab, Chlorambucil + Rituximab
Chlorambucil + Obinutuzumab is best; Both obinutuzumab and rituximab are anti-CD20
What second line agent for GBMs is notorious for causing delayed myelosuppression i.e. 6 weeks or more
Carmustine (BCNU); first line is surgery + temozolomide
True or False: Patients on Sunitinib for RCC who develop moderate HTN should stop the drug
False, it is expected that the drug will cause HTN and this predicts for a good outcome
Studies have shown that trastuzumab given in pregnancy can cause this issue
Oligohydramnios
What clinical setting is Glucarpidase used? MOA?
it is a recombinant carboxypeptide that converts methotrexate to glutamate; used in patients who have elevated MTX levels and renal dysfxn; goal MTX level <0.05
AML with MLL gene rearrangements can occur after exposure to what chemotherapeutics? Mutation?
Etoposide (topoisomerase II inhibitors, also doxorubicin which is a topoisomerase II inhibitor); 11q23 cytogenetic abnormality
What second generation 5 HT3 receptor antagonist is approved for both immediate and delayed nausea and vomiting?
Palonosetron; has half life of 40 hours
What medication can counteract potential tissue necrosis of anthracycline extravasation?
Dexrazoxane
What are the effects of DNA methylation and acetylation on DNA transcription?
Methylation silences genes so hypomethylating agents help undo that; acetylation promotes transcription so HDAC inhibitors help prevent de-acetylation
What is the concern with giving methotrexate in the setting of an effusion (any)?
MTX will sequester the into the fluid and stay there, so patients will have prolonged exposure (increased AUC) and therefore toxicities
Name 4 Microtubule Stabilizing agents (that prevent depolymerization)
Paclitaxel, Docetaxel, Nab-Paclitaxel, and Ixabepilone
What is the toxic metabolite of cyclophosphamide? What is the MOA of Mesna?
Acrolein; Mesna donates a thiol group to acrolein to neutralize it
What are some adverse effects of taxanes at toxic levels? How are they cleared?
Fluid retention, effusions and myelosuppression; hepatically cleared so careful if elevated bilirubin i.e. hepatic met
What two enzymes are affected by methotrexate? What other one is affected by pemetrexed?
Dihydrofolate reductase and thymidylate synthase; glycinamide ribonucleotide formyltransferase
Arthralgias are most commonly caused by what breast cancer drugs?
Aromatase Inhibitors such as anastrazole and lestrozole
What is Abraxane?
Nab-Paclitaxel (Nanoparticle Albumin Bound Paclitaxel)
What infection do you need to test for anytime you are considering starting rituximab?
HBV if either HbSAg or HBcAg is positive check viral load with PCR and start entacavir and refer to gastroenterology
What is the MOA of HDAC inhibitors?
By inhibiting HDACs they promote acetylation of histones; histone acetylation releases histones from DNA making transcription easier so you can transcribe more tumor suppressor genes that have been silenced
