Oncology II pt 2 Flashcards by Jimmy Hayden

What phase of the DNA replication cycle to topoisomerase I inhibitors work?

S phase

Prevents coiling and uncoiling of double-stranded DNA helix

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Irinotecan class, brand, unique concerns, boxed warnings

Topoisomerase I inhibitor
Acute cholinergic symptoms (treat with atropine)
Delayed diarrhea (treat with loperamide, up to 24 mg/day)
Pharmacogenomic conerns: patients homozygous for the UGT1A1*28 allele are at increased risk for neutropenia and delayed diarrhea

Boxed warnings for diarrhea lmao ok

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What phase of the DNA replication cycle to topoisomerase II inhibitors work?

G2 phase

Blocks coiling and uncoiling of double stranded DNA phase

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Etoposide class, unique concerns

Topoisomerase II inhibitor
Comes IV or capsules

IV: Toposar requires concentration of less than 0.4 mg/mL
Etopophos doesn’t have concentration limits, use in pts on fluid restriction

Etoposide capsules (Vepesid) are refrigerated. IV:PO ratio is 1:2

Boxed warning for myelosuppression, can have hypersensitivity reactions

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During what phase do pyrimidine analog antimetabolites work?

S phase
Active metabolute (F-UMP) incorporated into RNA to replace uracil and inhibits cell growth

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Fluorouracil class, brand, unique concerns

Pyrimidine analog antimetabolite
Adrucil, Efudex

Give leucovorin to increase efficacy
Dihydropyrimidine dehydrogenade (DPD) deficiency increases risk of severe toxicity

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Capecitabine class, brand, unique concerns

Pyrimidine analog antimetabolite
Xeloda
Oral prodrug of fluorouracil
DPD deficiency increases risk of severe toxicity

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Folate antimetabolites act during what phase of the cell cycle?

S phase

DNA synthesis

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Leucovorin place in therapy

Methotrexate, “rescue” must be given with high doses of MTX (> 500 mg/m2)
Also given with 5-FU to increase efficacy

Note: LEVOleucovorin is also available, dosed at 1/2 the dose of leucovorin

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Methotrexate brand, unique concerns

Trexall, Oltrexup, Rasuvo, Xatmep
May require leucovorin rescue if dose exceeds >500 mg/m2

Doses for cancer much higher than RA or psoriasis

Hydration and IV sodium bicarbonate must be given to alkalinize the urine and decrease risk of nephrotoxicity

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Drug interactions w MTX

NSAIDs, salicylates

Decreases clearance of methotrexate

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Tretinoin unique concerns

Absolutely contraindicated in pregnancy
Boxed warning for RA-APL differentiation syndrome “potentially fatal complication of induction chemotherapy in patients with acute promyelocytic leukemia (APL)”

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Arsenic trioxide unique concerns

QT prolongation

Boxed warning: RA-APL differentiation syndrome, QT prolongation

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Asparaginase, pegasparagase unique concerns, side effects

Hypersensitivity reactions, pancreatitis, prolonged prothrombin time (PT/INR)

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Bleomycin unique concerns

Not myelosuppressive
Maximum lifetime dose of 400 units due to pulmonary toxicity risk
Boxed warning for pulmonary fibrosis
Side effects: hypersensitivity reaction

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Everolimus concerns, side effects

CYP3A4 major substrate
Side effects dyslipidemia, rash, stomatitis, interstitial lung disease

Note: Brand for cancers Afinitor, Afinitor Disperz. Zortress is indicated for transplantation

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Temsirolimus unique concerns, side effects

Use non-PVC bag and tubing due to leaching of DEHP

Side effects: dyslipidemia, hyperglycemia, myelosuppression, interstitial lung disease

Revlimid generic, class, warnings, side effects

Lenalidomide
Immunomodulator
Like thalidomide - SEVERE birth defects, only available with restricted distribution, must be registered with REMS program
Consider prophylactic anticoagulation due to risk of DVT/PE and seek medical care if symptoms develop

Boxed warning: fetal risk/pregnancy

Side effects: neutropenia, thrombocytopenia

Pomalyst generic, class, warnings, side effects

Pomalidomide
Immunomodulator
Like thalidomide - SEVERE birth defects, only available with restricted distribution, must be registered with REMS program
Consider prophylactic anticoagulation due to risk of DVT/PE and seek medical care if symptoms develop

Boxed warning: fetal risk/pregnancy

Side effects: neutropenia, thrombocytopenia

Thalomid generic, class, warnings, side effects

Immunomodulator
Thalidomide

SEVERE birth defects, only available with restricted distribution, must be registered with REMS program
Consider prophylactic anticoagulation due to risk of DVT/PE and seek medical care if symptoms develop

Boxed warning: fetal risk/pregnancy

Side effects: neutropenia, thrombocytopenia

Velcade class, generic, unique concerns, contraindications, side effects

Bortezomib
Proteasome inhibitor
Give antiviral (acyclovir, valacyclovir) to prevent herpes (zoster and simplex) reactivation

Contraindications: hypersensitivity to boron or mannitol, intrathecal administration (fatal)

SIde effects: peripheral neuropathy, thrombocytopenia, neutropenia

Kyprolis class, generic, unique concerns, contraindications, side effects

Proteasome inhibitor
Premedicate with dexamethasone and fluids
Increased alkaline phosphatase = increased efficacy

Side effects: peripheral neuropathy (but less than bortezomib)

Different substems in monoclonal antibodies and their meanings

ci = circulatory system (bevacizumab, ramucirumab) = inhibits blood vessel growth

tu = tumor (cetuximab, pertuzumab) = targets cells on tumors

li = immune system (ipilimumab, nivolumab) = amps up patients immune system

Avastin generic, drug class, concerns, boxed warnings, side effects

Bevacizumab

VEGF inhibitor, ci=circulatory, impairs blood vessel growth (therefore can cause HTN, proteinuria, impaired wound healing due to dec blood flow)

Impairs wound healing - do not give 28 days before or after surgery

Boxed warnings = severe/fatal bleeding, GI perforation
Side effects = HTN

Cyramza generic, drug class, concerns, boxed warnings, side effects

Ramucirumab VEGF inhibitor, ci=circulatory, impairs blood vessel growth (therefore can cause HTN, proteinuria, impaired wound healing due to dec blood flow) Impairs wound healing - do not give 28 days before or after surgery Boxed warnings = severe/fatal bleeding, GI perforation Side effects = HTN

Herceptin generic, drug class, concerns, boxed warnings, side effects

Trastuzumab HER2 inhibitor tu=tumor Monitor LVEF at baseline and during treatment (echo or MUGA scan) Boxed warnings: HF, embryo-fetal death/birth defects - avoid pregnancy x 7 months after receiving Side effects = none underlined, usual (infusion related rxns, n/v/d, alopecia)

Pertuzumab drug class, concerns, boxed warnings, side effects

HER2 inhibitor tu=tumor Monitor LVEF at baseline and during treatment (echo or MUGA scan) Boxed warnings: HF, embryo-fetal death/birth defects - avoid pregnancy x 7 months after receiving Side effects = none underlined, usual (infusion related rxns, n/v/d, alopecia)

Kadcyla generic, drug class, concerns, boxed warnings, side effects

Ado-trastuzumab emtansine (trastuzumab conjugated to a microtubule inhibitor) HER2 inhibitor tu=tumor Monitor LVEF at baseline and during treatment (echo or MUGA scan) Boxed warnings: HF, embryo-fetal death/birth defects - avoid pregnancy x 7 months after receiving Side effects = none underlined, usual (infusion related rxns, n/v/d, alopecia) Also has additional side effects vs others in its class: myelosuppression, hepatotoxicity, neuropathy, pulmonary toxicity (none underlined) NOT interchangeable with conventional trastuzumab

Erbitux generic, drug class, concerns, boxed warnings, side effects

Cetuximab EGFR inhibitor, tu=tumor Premedicate 1st dose w diphenhydramine Test for EGFR expression and KRAS mutation MUST be KRAS wild type to use (predicts poor response if mutated in colorectal cancer); EGFR expression = better response rates NSCLC Boxed warnings: severe/fatal infusion-related reactions including cardiac arrest with cetuximab specifically

Vectibix generic, drug class, concerns, boxed warnings, side effects

Panitumumab EGFR inhibitor, tu=tumor Premedicate 1st dose w diphenhydramine Test for EGFR expression and KRAS mutation MUST be KRAS wild type to use (predicts poor response if mutated in colorectal cancer); EGFR expression = better response rates NSCLC Boxed warnings: severe/fatal infusion-related reactions; dermatological toxicities with panitumumab specifically

Rituxan generic, drug class, concerns, boxed warnings, side effects

Rituximab CD antigen inhibitor, tu=tumor Must be CD20 positive to use No underlined box warnings, side effects Can reactivate hepatitis B Rituximab can cause severe/fatal infusion-related reactions (SJS/TEN)

Blincyto generic, drug class, concerns, boxed warnings, side effects

Blinatumomab (tu=tumor) CD antigen inhibitor Must be CD19 nd CD3 positive for use Nothing underlined but name/generic was bolded?

Ketruda generic, drug class, concerns, boxed warnings, side effects

Pembrolizumab li = immune system, activates PD-2 inhibitor Nothing underlined, needs med guide....immune-mediated toxicities (bc it activates immune system) so colitis, hepatotoxicity, pulmonary toxicity, etc...

Opdivo generic, drug class, concerns, boxed warnings, side effects

li = immune system, activates PD-2 inhibitor Nothing underlined, needs med guide....immune-mediated toxicities (bc it activates immune system) so colitis, hepatotoxicity, pulmonary toxicity, etc...

Yervoy generic, drug class, concerns, boxed warnings, side effects

Ipilimumab CTLA-4 inhibitor, "removes brake" from T-cell activation Nothing underlined REMS program

Tyrosine kinase - general info, unique concerns

Orally administered Oral bioavailability may be altered with food, very important for patients to follow dosing instructions Pharmacogenomic testing must be done to determine whic patients will likely respond to these agents

Gleevec generic, drug class, concerns, boxed warnings, side effects

Imatinib Must be BCR-ABL (philadelphia chromosome) positive to use Side effects: fluid retention HBV reactivation

Take with food or within 1 hour after a meal

Imatinib Thalidomide Capecitabine Exemestane

Take on empty stomach (1 hour before or 2 hours after food)

``` Nilotinib Erlotinib Sorafenib Temzolomide Abireterone Pomalidomide ``` Pomalidomide take 2 hours before or 2 hours after oof

Take without regard to food

``` Dasatinib Sunitinib Tamoxifen Anastroazole Bicalutamide Lenalidomide Letrozole ```

Oral teratogenic anticancer agents

Thalidomide Pomalidomide Lenalidomide