X - CHEMOTHERAPEUTIC DRUGS

Question 1

Forms DNA cross-links, resulting in inhibition of DNA synthesis and function, Cell-cycle nonspecific

Answer 1

Alkylating agents

*Alkylating agents are inserted in the DNA of the cancer cells. They will cause chain termination because the cancer cell will lack 3’OH. As a general concept, in terms of side effect they will cause bone marrow suppression (take a look at the following alkylating agents to appreciate this generality. Bone marrow suppression manifested by pancytopenia)

Question 2

Alkylating agents

Answer 2

• CYCLOPHOSPHAMIDE [D], IFOSFAMIDE [D], CHLORAMBUCIL [D], MECHLORETHAMINE [D]
• CISPLATIN [D], CARBOPLATIN [D], OXALIPLATIN [D]
• PROCARBAZINE [D]
• DACARBAZINE [C]
• BUSULFAN [D]
• CARMUSTINE [D]

Question 3

SE: bone marrow suppression, hemorrhagic cystitis, hepatotoxicity, alopecia, SIADH, pulmonary toxicity

Answer 3

Cyclophosphamide

*Rescue therapy is MESNA. Cystitis can be prevented with adequate hydration

Question 4

Rescue therapy for cyclophosphamide

Answer 4

MESNA (TOPNOTCH)

Question 5

Rescue therapy for Cisplatin

Answer 5

Amifostine (TOPNOTCH)

Question 6

MOA: Forms hydrogen peroxide, which generates free radicals that cause DNA strand scission. Cell cycle nonspecific.

• can penetrate the CSF, For Hodgkin’s lymphoma, non-hodgkin’s lymphoma, brain tumors

Answer 6

Procarbazine

* Procarbazine has the highest carcinogenic potential amongst alkylating agent. Imagine an anticancer drug that can actually cause cancer. This one is to remember.

Question 7

SE: pulmonary fibrosis, adrenal insufficiency, skin pigmentation

Answer 7

Busulfan (TOPNOTCH)

Question 8

Highly lipophilic allowing ease of passage through BBB into the CNS ; For brain tumors, melanoma, skin cancer

Answer 8

Carmustine, lomustine (TOPNOTCH)

Question 9

Inhibits dihydrofolate reductase, decreases synthesis of thymidylate, amino acids, purine nucleotides; cell cycle specific

Answer 9

Methotrexate (TOPNOTCH)

Question 10

Rescue therapy for methotrexate

Answer 10

Leucovorin (Folinic acid) (TOPNOTCH)

Question 11

MOA: Inhibits de novo purine nucleotide synthesis. Activated by HGPRT. Cell cycle specific.

USES: Acute leukemias (AML, ALL), Chronic myelogenous leukemia, Lymphomas

Answer 11

6-MERCAPTOPURINE [D], 6-THIOGUANINE [D], AZATHIOPRINE [D]

Question 12

Inhibits thymidylate synthase, causes thymineless death of cells, cell cycle specific

Answer 12

5-Fluorouracil (TOPNOTCH)

Question 13

Inhibits DNA synthesis and repair. Inhibits ribonucleotide reductase with reduced formation of dNTPs. Cell-cycle specific.

Answer 13

Antimetabolite (pyrimidine): GEMCITABINE [D], CAPECITABINE [D]

* Gemcitabine is an evolution of antimetabolite because it can be used for solid tumors. Think of Pancreatic cancer as the most common indication.

Question 14

MOA: Inhibits DNA synthesis and repair. Inhibits ribonucleotide reductase with reduced formation of dNTPs. Cell-cycle specific.

Most specific for the S-phase of the cell cycle

USES: Acute leukemias (AML, ALL), CML in blast crisis

Answer 14

Cytarabine

Question 15

Prevents microtubule assembly, causes cell arrest at metaphase, cell cycle specific

Answer 15

Vinca alkaloid: Vincristine, Vinblastine

* Vincristine will not likely cause bone marrow suppression rather it will cause neuropathy. Vincristine will cause crispy nerves.

* vinBLASTine BLASTS the Bone marrow. vinblastine causes myelosuppression

Question 16

Inhibits DNA topoisomerase II (DNA Gyrase). Inhibits mitochondrial electron transport. Cell cycle specific.

Answer 16

Class: Podophyllotoxin

ETOPOSIDE [D], TENIPOSIDE [D]

SE: Bone marrow suppression, GI irritation, Alopecia

Question 17

MOA: Inhibits topoisomerase I. Cell cycle specific.

Answer 17

Class: Camptothecin

TOPOTECAN [D], IRINOTECAN [D]

Topotecan: Advanced ovarian cancer (2nd line), Small cell lung cancer

Irinotecan: Metastatic colorectal cancer (MNEMONIC: Irinotecan! Inire! Inire! Colorectal cancer)

Question 18

Interferes with mitotic spindle, prevents microtubule DISASSEMBLY into tubulin monomers, cell cycle specific

Answer 18

PACLITAXEL [D], DOCETAXEL [D], CABAZITAXEL [D]

NOTE: They will prevent microtubule DISASSEMBLY. What drugs will inhibit microtubule ASSEMBLY? VINCRISTINE AND VINBLASTINE!!!

Question 19

Used in Advanced breast and ovarian cancers, lung cancer, gastroesophageal cancer, gastric cancer, prostate cancer, bladder cancer, head and neck cancer

Answer 19

Paclitaxel, docetaxel (TOPNOTCH)

Question 20

Acts primarily in M phase of cancer cell cycle

Answer 20

Vinca alkaloid: Vincristine, Vinblastine (TOPNOTCH)

Question 21

Intercalates between base pairs. Inhibits topoisomerase II. Generates free radicals → single and double-stranded DNA breaks. Cell cycle non-specific.

Answer 21

• Anthracycline: Doxorubicin, daunorubicin, idarubicin, epirubicin, mitoxantrone (TOPNOTCH)
• Side effects: Alopecia, Nausea, Vomiting, Dilated Cardiomyopathy, Congestive heart failure, red urine (Doxorubicin), myelosuppression
• Rescue therapy is DEXRAZOXANE

Question 22

Rescue therapy for Doxorubicin

Answer 22

dexrazoxane (TOPNOTCH)

Question 23

Most specific for the G2 phase of cell cycle

Answer 23

Bleomycin (TOPNOTCH)

Question 24

Generates free radicals, which cause DNA strand breaks. Intercalates with DNA. Cell cycle specific.

SE: Pneumonitis, Pulmonary fibrosis, Mucocutaneous reactions (blisters, hyperkeratosis), Alopecia, Hypersensitivity, Fever and chills , hypotension

Answer 24

BLEOMYCIN [D], MITOMYCIN [D]

Question 25

Binds to double stranded DNA, **inhibits DNA-dependent RNA synthesis**, cell cycle non-specific

Answer 25

**Actinomycin D** (TOPNOTCH) \*Other name of actinomycin is **dactinomycin**. It is the oldest antitumor antibiotic.

Question 26

MOA: Inhibits **tyrosine kinase activity** of the protein product of **bcr-abl** oncogene in **CML**. Inhibits c-kit tyrosine kinase in **GIST**.

Answer 26

Tyrosine Kinase Inhibitors: **IMATINIB [D], DASATINIB [D], NILOTINIB [D], CRIZOTINIB [D], AFATINIB [D], NINTEDANIB [D], REGORAFENIB [D]**

Question 27

MOA: Acts against breast cancer cells that overexpress the **HER-2/neu receptor** for epidermal growth factor

Answer 27

Monoclonal antibody: **TRASTUZUMAB [B], PERTUZUMAB [D], LAPATINIB [D]** \*Just like doxorubicin, it can cause **cardiomyopathy**. This drug has a trade name **Herceptin**. MNEMONIC: Heartceptin or if you want Trastuzumab “tinuzuk ang puzu”

Question 28

MOA: Inhibits binding of **VEGF to VEGFR** leading to inhibition of VEGF signaling. **Inhibits tumor vascular permeability** but enhances tumor blood flow and drug delivery.

Answer 28

**Bevacizumab** SIMD: SORAFENIB [D], SUNITINIB [D], PAZOPANIB [D], LENVATINIB [D] \* MNEMONIC: BV BeVacizumab for blood vessel. It inhibits angiogenesis!

Question 29

Binds to a surface protein in NHL cells, induces complement-mediated lysis, direct cytotoxicity and induction of apoptosis

Answer 29

Rituximab (TOPNOTCH)

Question 30

Endogenous glycoproteins with antineoplastric, immunosuppressive and antiviral actions

Answer 30

Interferon alpha (TOPNOTCH)

Question 31

Depletes serum asparagines ; For ALL, T-cell auxotrophic CA (leukemia and lymphomas) that require asparagine for growth

Answer 31

Asparaginase (TOPNOTCH)

Question 32

**Only vitamin that can cure cancer** MOA: Allows DNA transcription and differentiation of immature leukemic promyelocytes into mature granulocytes (differentiation therapy).

Answer 32

**All-Trans retinoic acid** REVIEW: * What leukemia is this drug used? **ACUTE PROMYELOCYTIC LEUKEMIA!!** * What do you call the needle-like azurophilic granules seen in APL? **AUER RODS!!** * What do you call cells with numerous auer rods? **FAGGOT CELLS!!** * **t(15;17)!!!!!**

Question 33

For acute promyelocytic leukemia

Answer 33

All-Trans retinoic acid (TOPNOTCH)

Question 34

Suppresses inflammation and immune response, may trigger apoptosis and work on nondividing cancer cells

Answer 34

Prednisone (TOPNOTCH)

Question 35

Estrogen **antagonist** actions in **breasts tissue and CNS** Estrogen **agonist** effects in **uterus, liver and bone**

Answer 35

Selective Estrogen Receptor Modulator: **TAMOXIFEN** [D], TOREMIFENE [D] \*Prevents osteoporosis in post-menopausal women and decreases risk of atherosclerosis at the risk of causing endometrial cancer. FLUVESTRANT is a FULL ESTROGEN RECEPTOR ANTAGONIST (No agonist effect) used in hormone receptor positive metastatic breast cancer. Torimefene is structurally related to Tamoxifen

Question 36

Androgen antagonist ; For prostate cancer

Answer 36

Flutamide (TOPNOTCH)

Question 37

Increased LH, FSH secretion with intermittent administration, reduced LH and FSH secretion with prolonged continuous administration ; For prostate cancer

Answer 37

**GnRH Analog: LEUPROLIDE [D], GONADORELIN [B], NAFARELIN [X]** \* Must be co-administered with **flutamide (androgen antagonist)** to prevent tumor flare-up on initiation of treatment

Question 38

Reduces estrogen synthesis by inhibiting aromatase; For breast cancer

Answer 38

Anastrazole (TOPNOTCH)

Question 39

Effective againsts breast cancer that have become resistant to tamoxifen

Answer 39

Anastrazole (TOPNOTCH)

Question 40

Causes **Nephrotoxicity and acoustic nerve damage**

Answer 40

**Cisplatin, Carboplatin**

Question 41

Causes **peripheral neuropathy**

Answer 41

**VIncristine**

Question 42

Causes **cardiotoxicity**

Answer 42

**Doxorubicin (Dilated cardiomyopathy) and Transtuzumab**

Question 43

Causes **pulmonary fibrosis**

Answer 43

**Bleomycin**

Question 44

Causes **hemorrhagic cystitis**

Answer 44

**Cyclophosphamide**

Question 45

Causes **myelosuppression**

Answer 45

**Methotrexate, 5 FU, 6 Mercaptopurine**