Cancer Chemotherapy Flashcards by Serinna Singh

List 3 characteristics of a cancer cell

Define one characteristic that distinguishes a benign tumor from a malignant one

Uncontrolled growth + survival

Angiogenesis

Invasion + metastasis **

** What Malignant tumor has that benign one doesnt

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Name 3 major classes of non-targeted chemotherapies

Match them with the phase(s) in cell cycle

Inhibitors of mitotic spindle function = M phase

Inhibitors of DNA synthesis = S phase

Agents that cause severe DNA damage = S or any phase

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For cancer-cell specific targeted chemotherapy, which targets

Inc. proliferation / survival
Inc. angiogenesis

Inc. proliferation/survival
EGFR
BCR-ABL

Inc. angiogenesis
VEGFR

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What does EGFR do?

Activates cell proliferation through proteins that activate RAS

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What does BCR-ABL do?

Unique constitutively active tyrosine kinase that promotes proliferation and prevents apoptosis

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What does VEGFR do?

Initiates signal cascades that stimulate angiogenesis

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Where is the mostly likely location in the cell cycle for the action of targeted chemotherapies?

Between G0 and G1

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What is the affected cell type responsible for fatigue?

RBC

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What is the affected cell type responsible for bleeding from the GI and genitourinary tract?

Platelets

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What is the affected cell responsible for the increased risk of infections?

Neutrophils

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What is the affected cell type responsible for hair loss?

Hair follicles

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What is the affected cell type responsible for diarrhea?

GI epithelial cells

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What are general AEs of non-targeted chemotherapies?

GI cells =
+diarrhea
+mucositis
+N/V

Bone marrow cells =
+dec. WBC = leukopenia
+dec. platelets = thrombocytopenia
+dec. RBCs = anemia

Hair follicles = alopecia

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What does pacytopenia refer to?

Leukopenia + thrombocytopenia + anemia

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What drug classes are inhibitors of mitotic spindle function?

Vinca-alkaloids

Taxans

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What are examples of Vinca-alkaloids?

What is their MOA?

Vincristin

Vinblastin

Inhibit MT polymerization

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What are examples of Taxans?

What is their MOA?

Paclitaxel

Docetaxel

Inhibit MT DEpolymerization

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What are AEs of MT inhibitors ?

Neurotoxic = peripheral neuropathy

Hypersensitivity reactions
**mainly PACLITAXEL

Constipation
****mainly VINCRISTINE

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What drug classes inhibit DNA synthesis?

Are they non-targeted or targeted?

Non-targeted

Inhibitors of purine/pyrimidine synthesis

Inhibitors of deoxyribonucleotide synthesis

DNA intercalated

Topoisomerase inhibitors/DNA cleaving agents

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What are drugs that inhibit purine/pyrimidine synthesis?

6-Mercaptopurine (6-MP)

Methotrexate (MTX)

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What is the MOA of 6-MP?

Inhibits de-novo purine synthesis

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What is an AE of 6-MP?

Hepatotoxicity

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What is a DDI associated with 6-MP?

Why?

Allopurinol

This will inhibit the XO enzyme which usually metabolizes 6-MP into inactive moieties.. allopurinol onboard means more 6-MP gets diverted to the enzyme that will break it down into the active moiety

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What is the MOA of MTX?

Inhibits de novo purine synthesis

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What drugs inhibit deoxyribonucleotide synthesis?

5-fluorouracil MTX Hydroxyurea

What is the MOA of 5-FU?

Inhibits thymidylate synthase

What AE is associated with 5-FU?

Hand-foot syndrome

What is the MOA of MTX? | Inhibition of deoxyribonucleotide synthesis

Inhibits thymidylate synthase Inhibits de-novo purine synthesis

What AE is associated with MTX?

Hepatotoxicity (BB warning) Bone marrow suppression (BB warning)

When is MTX contraindicated?

Pregnancy (BB warning)

What is leucovorin rescue therapy? When it is given?

Activated folic acid Given to limit toxicity since MTX inhibits the activation of DHF to the active folic acid (THF) form

What is the MOA of hydroxyurea?

Inhibits ribonucleotide reductase

What drugs are DNA intercalators?

Doxorubicin Daunorubicin Dactinomycin

What is the MOA of DNA intercalators?

Intercalate with DNA, disrupt progress of replication fork in order to distort helix

What AE is associated with DNA intercalators ?

Cardiotoxicity: cardiomyopathy

What is a prevention for the cardiotoxicity AE associated with DNA intercalators?

Dexrazoxane (iron chelation)

What drugs are topoisomerase inhibitors/ DNA clearing agents?

Topotecan Etoposide Bleomycin

What is the MOA of topoisomerase inhibitors?

Inhibit topoisomerase = DNA strand breaks = apoptosis

What AE is associated with topoisomerase inhibitors ?

Severe diarrhea

What is the MOA of bleomycin?

Produces single strand/double strand breaks by complex mechanisms involving bleomycin, oxygen, and ferrous iron

What AE is associated with bleomycin?

Pulmonary fibrosis | Major limitation

What drug class agents induce structural DNA damage? Are they cell-cycle specific?

Non-cell cycle specific Alkylation agents Platinum agents

What drug is an example of an alkylation agent?

Cyclophosphamide

What is the MOA of cyclophosphamide?

Alkylate DNA = cross-linking = strand break = apoptosis

What AE is associated with cyclophosphamide?

Hemorrhagic cystitis (bleeding, inflammation in bladder) - due to formation of acrolein toxic metabolite Secondary malignancies Gonadotoxic

What is a prevention treatment against hemorrhagic cystitis?

Extensive hydration MESNA (binds to acrolein)

What is a platinum agent?

Cisplatin

What is the MOA of cisplatin?

Forms platinum adduct to cross-link guanines = apoptosis

What AE is associated with cisplatin?

Nephrotoxicity Ototoxicity = tinnitus, hearing loss

What is prevention for nephrotoxicity from cisplatin?

Hydration Amifastin (generates thiol metabolite that scavengers free radical)

What drug classes are examples of TARGETED chemotherapies?

Tyrosine kinase inhibitors (TKIs) Monoclonal antibodies (mabs)

What are examples TKIs and their targets?

Erlotinib, Gefitinib = EGFR tyrosine kinase Imatinib, dasatinib, nilotinib = BCR-Abl tyrosine kinase Sunitinib = VEGFR tyrosine kinase

What AEs are associated with EGFR TKIs?

Rash Steven Johnsons syndrome Diarrhea

What AEs are associated with BCR-Abl TKIs?

GI Hepatotoxicity ``` QT prolongation (BB warning) ****NILOTINIB ```

What AEs are associated with VEGFR TKIs?

Hepatotoxicity (BB warning) HTN* Thromboembolism* *"class effect" of VEGFR targeting drugs

What does VEGF do?

Stimulates NO production by endothelial cells

What are types of MABs and their targets?

Cetuximab = EGFR Trastuzumab = HER-2 (also growth factor) Bevacizumab = VEGFR

What AE is associated with Cetuximab?

Rash GI effects

What AE is associated with Trastuzumab?

Cardiotoxic | Dec. LV ejection fraction

What AEs are associated with Bevacizumab?

HTN Thromboembolism

If a patient presented with the following, what would you diagnose as: ``` Tachycardia SOB Neck vein distension Pulmonary rales Enlarged heart on echo ```

Cardiomyopathy

If a patient presented with the following, what would you diagnose as: Painful urination, frequency and he matures

Hemorrhagic cystitis

If a patient presented with the following, what would you diagnose as: Cough Dyspnea Rales

Pulmonary fibrosis

If a patient presented with the following, what would you diagnose as: Numbness of hands and feet

Peripheral neuropathy

If a patient presented with the following, what would you diagnose as: Creatinine clearance 75 ml/min serum (declines from 110 ml/min @ baseline) magnesium (1.2 mEq/l)

Nephrotoxicity

What drug could cause cardiomyopathy?

Doxorubicin

What prevention is possible for cardiomyopathy?

Limit cumulative dose Dexrozaxane Liposomal preparations

What is treatment available for toxicity from doxorubin leading to cardiomyopathy?

BBs ACEIs ARBs Diuretics

What drug can cause hemorrhagic cystitis?

Cyclophosphamide

Is prevention for hemorrhagic cystitis AE possible? What tx is available?

Prevention: Forced hydration OR MESNA Tx: D/c and start hydration

What drug can cause pulmonary fibrosis?

Bleomycin

Is prevention of pulmonary fibrosis from bleomycin preventable? What tx is available?

No. Tx: D/c med Oxygen + steroids

What drugs can cause peripheral neuropathy?

Vinca-alkaloids | Taxans

Is prevention possible for the peripheral neuropathy AE from vinca-alkaloids and taxans? What tx is available ?

No Tx: Pain meds for neuropathy = gabapentin, amitryptiline, fluoxetine

What drug could cause nephrotoxicity?

Cisplatin

Is Cisplatin - caused nephrotoxicity possible to prevent? What tx is available?

Possible prevention: Aggressive hydration Amifastin ``` Tx: IV saline Lower dose Switch to other platinum drugs Oral Mg supplement ```

What is an advantage of a TKI vs. MAB?

TKIs are available oral, while MABs are only IV or IM!