Platinum compound toxicities for: - cisplatin - oxaliplatin

- cisplatin: neuro and renal - oxaliplatin: neuro (low renal tox)

Cancer Pharmacology Flashcards by Erica Silva

Antimetabolites: ___, ___ and ___

Antifolates, Purine, and Pyrimidine Analogs

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Microtubule inhibitors: ___ and ___

Vinca alkaloids and taxanes

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Topoisomerase inhibitors: ___ and ___/___

“Tecans”, and Anthracyclins/Etoposide

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Topoisomerase I Inhibitor: ___

Tecans

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Topoisomerase II Inhibitor: ___, ___

Anthracyclins, Etoposide

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Cyclophosphamide is a ___.

DNA alkylating agent.

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Cyclophosphamide is used for

Breast cancer and lymphoma

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Resistance to cyclophosphamide arises through

detoxification by thiols, increased DNA damage repair, and increased drug metabolism.

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Cyclophosphamide toxicities of note

Intertility/mutagenesis

Hemorrhagic cystitis

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How do you prevent hemorrhagic cystitis with alkylator treatment?

Thiols

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Cisplatin and Oxaliplatin are

DNA Damaging Agents (Platinum compounds)

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Cisplatin is used for

Lung and testicular cancer, among others.

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Oxaliplatin is used for

Colorectal cancers.

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___ can be used as radiosensitizers.

Platinum compounds.

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Platinum compound toxicities for:

cisplatin
oxaliplatin

cisplatin: neuro and renal

- oxaliplatin: neuro (low renal tox)

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Methotrexate is an

Anti-metabolite (folic acid analog).

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Ara-C, 5’FU, and Gemcitabine are

Pyrimidne analogs.

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Methotrexate is used for for

Leukemia, lymphoma, and immunosuppression.

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Methotrexate toxicities of note

liver toxicity (hepatitis may develop)
pulmonary toxicity
toxic in utero

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Effects of methotrexate can be reversed with

Leukovorin/tetrahydrofolate

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Resistance arises to methotrexate through

1) Mutation/amplification of DHFR
2) Altered drug transport
3) Decreased polyglutamates

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Cytosine arabinoside (Ara-C) is an

Antimetabolite (pyrimidine analog).

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Resistance to Ara-C arises by

1) Delete activating enzyme

2) over-express metabolic enzymes

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Ara-C is used for

Leukemia and lymphoma

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Gemcitabine is a

antimetabolite (pyrimidine analog).

Resistance togemcitabine arises through

Deletion of the activating enzyme.

Notable toxicities of gemcitiabine

Flu-like syndrome | Edema

Gemcitabine is used for

Pancreatic cancer

5'FU is an

Anti-metabolite(blocks thymidylate synthase)

Resistance to 5'FU arises through

mutations of thymidylate synthase | loss of reduced folates (laukovorin improves)

Notable toxicities of 5'FU

Hand-foot syndrome | Diarrhea

5'FU is used for

GI malignancies (also esophageal cancer with radiosensitizer)

Vincristine is

microtubule inhibitors (block polymerization, vinca alkaloid).

Docetaxel is

microtubule inhibitors (stabilizers, taxanes).

Resistance to MT inhibitors arises though

MDR overexpression | tubulin mutations

Notable toxicities of vincristine:

Neurotoxicity

Vincristine is used for

leukemia, lymphoma

Notable toxicities of docetaxel

``` Neurotoxicity Hypersensitivity reactions (to the drug vehicle) ```

Docetaxel is used for

Lung, OvCa, Br, Pr

Irinotecan is a

Topo I inhibitor ("Tecans", causes SSB)

Doxorubicin is a

Topo II inhibitor (Anthracyclin, causes DSBs, also causes other dna damage and free radicals)

Resistance to doxorubicin arises through

MDR expression

Notable toxicities of doxorubicin

Cardiac toxicity | Skin toxicity if not given by IV

Cardiac toxicity of doxorubicin can be prevented by treating with

dexrazoxane

Doxorubicin is used for

Lymphomas, leukemias, breast cancer.

Etoposide is a

TopoII inhibitor.

Resistance to etoposide arises through

MDR expression and Topo II mutation

Notable toxicities of etoposide

secondary leukemias

Etoposide is used for

testicular cancer.

Small molecule kinase inhibitors that block growth signaling pathways.

"ibs"

Antibodies that block/bind growth factor receptors/ligands or other cell surface molecules.

"abs"

EGFR blocker

Erlotinib | Lapatinib (blocks Her2 also)

Erlotinib is used for

Lung cancer with EGFR mutation and metastatic NSCL with EGFR mutation. Usually adenocarcinomas in nonsmoking east asian women.

Resistance to erlotinib arises from

mutation preventing drug from binding target

Notable side effects of erlotinib

Rash (acne-like), lung toxicity

ALK inhibitor

Crisotinib

Crisotinib toxicities

mild visual changes

Crisotinib is used to treat

Lung carcinoma with chromosomal rearrangement of ALK.

Blocks C-Abl, BCR-Abl, c-Kit, PDGFR

Imatinib (Desatinib/Nilotinib are 2nd gen)

Imatinib is used to treat

CML, CMML, and GIST. In GIST, Imatinib (adjuvant) postpones recurrence, increases survival, or (metastatic), high RR but resistance develops. Use desatinib.

Notable toxicities of imatinib

Fluid retention (2nd gen have cardiac tox.)

Cancer associated with c-Kit mutation:

GIST

Cancer associated with ALK mutation:

Lung carcinoma

Cancer associated with EGFR mutation:

Lung cancer, some breast cancers

VEGFR, PDGFR, c-Kit blocker

Sunitinib (Sorafenib also blocks Raf kinase) Both are "oral broad kinase inhibitors"

Sunitinib is used to treat

Metastatic renal cell carcinoma Sorafenib for HCC

Notable toxicities of sunitinib

Hypertension, TED, skin rash.

B-Raf inhibitor

Vemurafenib.

Cancer associated with B-Raf mutation:

melanoma with B-Raf mutation, combine with MEK inhibitor

Notable toxicities associated with Vemurafenib

Skin squamous cell carcinoma

Anti-CD20

Retiximab

Anti-Her2

Trastuzumab

Anti-EGFR

Cetuximab

Anti-VEGF

Bevacizumab

Resistance to Cetiximab and Trastuzumab

B-raf or Ras mutation

Low anti-tumor activity when used alone

Bevacizumab | Cetuximab

Retuximab is used to treat

B-NHL and B-CLL

Trastuzumab is used to treat

Breast cancer and some GI cancers

Cetuxumab is used to treat

Colon cancer (also head and neck)

Bevacizumab is used to treat

Colon, lung, and renal.

Notable toxicities of retuximab

Hep B reactivation, JV infecton

Notable toxicities of trastuzumab

Cardiac toxicity

Notable toxicities of cetuximab

Rash, lung toxicity, (also mg wasting)

Notable toxicities of bevacizumab

``` HTN CHF TED Hemorhage GI Perforation ```

Cancer associated with EGFR:

Colon, head and neck, also lung, pancreas

Notable toxicities of tamoxifen (3):

1) Increased risk of uterinecancer 2) Thromboembolic events 3) Hot flashes/uterine bleeding

Tamoxifen is used to treat

ER + breast cancer, including metastatic. | * also chemophophylaxis in high-risk women

Tamoxifen is a selective ___ of ER receptors in breast tissue, and selective ___ of ER receptors in uterine tissue and bone.

antagonist (breast) | agonist (uterus and bone)

Aromatase inhibitors ___ estrogen synthesis.

block

Notable toxicities of aromatase inhibitors (3):

1) osteoporosis and MSK pain 2) thromboembolic events 3) hot flashes and uterine bleeding

Aromatase inhibitors are used to treat

ER + breast cancer (first-line)

Anastrozole, letrozole, and exemestane are

Aromatase inhibitors.

Leuprolide and Goserelin are

GnRH agonists. They cause an initial surge in LH/FSH, but then inhibit gonadotropin release leading to suppression of estrogen (and testosterone) produced by ovaries.

Notable toxicities of GnRH agonist

1) disease flare (prevent with AR/ERblocker) 2) osteoporosis 3) loss of libido in male Others: hot flash, fatigue, anemia

GnRH agonists are used to treat

ER+ breast cancer (pre-menopausal with aromatase inhibitor) and prostate cancer (adjuvant, met).

Flutamide, bicalutamide, and enzalutamide are

AR blockers (competitive)

Notable toxicities of AR blockers

1) loss of libido 2) hot flashes 3) gynecomastia

AR blockers are used to treat

Met prostate cancer, wit GnRH agonist.

Lung cancer typical tx:

EGFR-TKI and Alk-inhibitor

Her2+ Breast cancer typical tx:

Trastusumab

NHL typical tx:

Retuximab

Breast/prostate cancer typical tx:

Estrogen/androgen blockade

Cancer Pharmacology Flashcards

(102 cards)