Onc Pharm Flashcards by Michael Robinson

Cisplatin

Alkylating Agent (all stages)
- cross links DNA

Acute: Nausea, Nephrotoxicity, Ototoxicity, EMETOGENIC

Delayed: IRREVERSIBLE NEUROTOXICITY

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Carboplatin

Alkylating Agent (all stages)
- cross links DNA

Acute: Nausea, Vomiting, Ototoxicity, Nephrotoxicity

Delayed: Myelosuppression

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Oxaliplatin

Alkylating Agent (all stages)

Acute: Family, Toxicities

Delayed: Reversible Neurotoxicity

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Busulfan

Alkylating Agent (all stages)

Acute: Nausea, Vomiting

Delayed: Pulmonary Fibrosis*, Myelosuppression

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Cyclophosphamide

Alkylating Agent (all stages)

Acute: Nausea, Vomiting

Delayed: Hemorrhagic Cystitis*, Myelosuppression

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Carmustine

Alkylating Agent (all stages)
(can cross BBB)

Acute: Nausea, Vomiting

Delayed: Myelosuppression, CNS Toxicity

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Procarbazine

Alkylating Agent (all stages)

Acute: Nausea, Vomiting

Delayed: Myelosuppression,
RISK OF SECONDARY MALIGNANCY
Adverse drug interactions with anti-depressants (b/c metabolites act as MAOinhibitors)

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Antimetabolites

Cell Cycle Specificity
Mechanism

S-Phase Specific

Interferes with DNA synthesis

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6-Mercaptopurine

Anti-Metabolite (S-Phase)

Purine Analog, Inhibits enzymes of purine synthesis

Myelosuppression*. Diarrhea
Thiopurine Methyl Transferase (TPMT) deficiency can result in severe toxicities

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Cladribine

Anti-Metabolite (S-Phase)

Purine Analog, Inhibits enzymes of purine synthesis

Myelosuppression, Immunosuppression (CD4, CD8)

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Cytarabine (Ara-C)

Anti-Metabolite (S-Phase)

Pyrimidine Analog (Hematologic Malignancies Only)
Inhibits DNA Polymerase*

Acute: GI
Chronic: Myelosuppression (panCYtopenia)
NOTE: Ara-CTP is a major cytotoxic metabolite

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5-Fluorouracil (5-FU)

Anti-Metabolite (S-Phase)

Pyrimidine Analog
FdUMP inhibits TS
FdUTP inhibits DNA synthesis
FUTP inhibits RNA processing

Catabolized by Dihydropyridine Dehydrogenase (DPD)
If DPD low in liver, TOXICITY is LIFE THREATENING

Myelosuppression, Neutotoxicity
Derm -> Hand-Foot Syndrome w/ continuous infusion

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Capecitabine

Anti-Metabolite (S-Phase)

Pro/Pro Drug
Metabolites converted to 5-FU in liver

Consider DPD levels

Myelosuppression, Neutotoxicity
Derm -> Hand-Foot Syndrome w/ continuous infusion

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Methotrexate

Anti-Metabolite (S-Phase)

Folic Acid Analog, Competitively inhibits DHFR and TS

Myelosuppression*
rescued by Leucovorin*

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Pemetrexid

Anti-Metabolite (S-Phase)

Folic Acid Analog, Inhibits TS

Myelosuppression, Skin Rashes, Mucositis, Diarrhea, Fatigue

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Gemcitabine

Anti-Metabolite (S-Phase)

Pyrimidine Analog
Inhibits DNA Poly, Blocks DNA/RNA repair, Chain Termination

Neutropenia, Hemolytic Uremic Syndrome (HUS)*

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Vinca Alkaloids

Mechanism, Phase

Inhibits microtubule polymerization by binding to beta-tubulin (preventing spindle formation)

Mitotic Phase Arrest (M Phase)

Vinblastine

Vinca Alkaloid (M-Phase)

Inhibits microtubule polymerization by binding to beta-tubulin (preventing spindle formation)

Potent Vesicant (blistering agent)*
Alopecia
Myelosuppression, Nausea, Vomiting

Solid Tumors, Leukemias
Hodgkin Lymphoma

Vincristine

Vinca Alkaloid (M-Phase)

Inhibits microtubule polymerization by binding to beta-tubulin (preventing spindle formation)

Peripheral neuropathy*
Autonomic Defects* (ortho. hypotension, urinary retention)
SIADH*
Myelosuppresion

Solid Tumors, Leukemias
Non-Hodgkin Lymphoma

Taxanes

Mechanism, Phase

Enhances microtubule polymerization (cannot break down)

M Phase

Paclitaxel

Taxane (M-Phase)

Enhances microtubule polymerization (cannot break down)

Hypersensitivity* (prevented with meds that dilute drug)
Peripheral Sensory Neuropathy*
Nausea, Vomiting

Abraxane

Taxane (M-Phase)

Enhances microtubule polymerization (cannot break down)

Paclitaxel formulated with albumin carrier - decreases toxicity
NO HYPERSENSITIVITY*

Docetaxel

Taxane (M-Phase)

Enhances microtubule polymerization (cannot break down)

Hypersensitivity* (prevented with meds that dilute drug)
Peripheral Sensory Neuropathy*
Nausea, Vomiting

Ixebepilone

Epothilone B Agent (M-Phase)

Binds tubulin and stabilizes microtubules

Myelosuppresion, Hypersensitivity, Neurotoxicity

Approved for Breast Cancer

Etoposide

Epipodophylotoxin Topoisomerase II Inhibitor (S-Phase) Alopecia, Myelosuppresion, GI

Topotecan

Camptothecan Topoisomerase I Inhibitor (S-Phase) APPROVED FOR SCLC* Alopecia, Myelosuppresion, GI

Irinotecan

Camptothecan Topoisomerase I Inhibitor (S-Phase) Pro-drug converted in the liver DIARRHEA (late can be severe)

Anthracycline (Anti-Tumor Antibiotic) Mechanism, Toxicity

``` Inhibit Topoisomerase II DNA intercalation (blocks RNA and DNA) -> Breaks DNA Binds to Cell Membranes Generates Semi-Quinone Free Radicals** (CARDIOTOXICITY) ```

Doxorubicin | Adriomycin

Anthracycline (Anti-Tumor Antibiotic) Used in combination therapy (ABVD for HL) IV Admin CARDIOTOXICITY* (generates free radicals that intercalate with DNA, break DNA) toxicity reduced with dexrazoxone (iron chelating) Myelosuppression, GI

Daunorubicin

Anthracycline | Anti-Tumor Antibiotic

Idarubicin

Anthracycline | Anti-Tumor Antibiotic

Mitocantrone

Anthracycline (Anti-Tumor Antibiotic) BLUE SCLERA and FINGERNAILS** Myelosuppression, GI, Alopecia

Mitomycin C

Antibiotic Activated by reduction All Phases Acts on tumor cells in Hypoxic Environment* Hemolytic Uremic Syndrome** GI

Bleomycin

Antibiotic Binds DNA - DS, SS Breaks G2 Specific Pulmonary Fibrosis

Retinoic Acid (ATRA)

Acute Promyelocytic Leukemia t(15;17) PML-RARa (AML, M3) Treatment leads to cell differentiation and death Leukocytosis Capillary Leak Syndrome (pulm edema ,resp failure) Renal Failure

Arsenic

Acute Promyelocytic Leukemia t(15;17) PML-RARa (AML, M3)

Imatinib

Tyrosine Kinase Inhibitor "Gleevec" BCR-ABL t(9;22) CML Binds to catalytic cleft in ABL (tyrosine kinas) Resistance from mutations that abrogate binding of drug

Dasatinib

Newer Tyrosine Kinase Inhibitor | Specifically to overcome imatinib resistance

Trastuzumab

"Herceptin" HER2 (Human Epidermal Growth Factor Receptor 2) ``` Tras2zumab = Her2 HeartCeptin = cardiotoxicity ```

Trastuzumab DM1

Toxin-Conjugated Trastuzumab Thrombocytopenia, Elevated Transaminases

Lapatinib

HER1, HER2 Competitive Inhibitor Rash, Diarrhea