Anticancer

Question 1

what is BUSULFAN (which is a non cell specific ALKYLATING agent used in CML therapy) main AE?

Answer 1

Profound MYELOSUPPRESSION

(additionally: Pulmonary fibrosis, skin pigmentation & seizures)

Question 2

first line anticancer treatment for TESTICULAR CANCER

-what phase of the cell cycle does this cell cycle specific drug effect?

Answer 2

BLEOMYCIN

G2 exclusiviely

Question 3

what is one of DOCETAXEL’s (taxane MT inhibitor) main AE’s?

Answer 3

Fluid retention:

Pre-treatment with Dexamethasone is required to prevent fluid retention.

Question 4

• Inhibits Angiogenesis.
• Inhibits VEGFR-1, VEGFR-2, and PDGFR.

name that drug

Answer 4

SUNITINIB

Question 5

What the main difference btw the AE profile of Vincristine vs Vinblastine

Answer 5

Vincristine’s main AE is associated with NEUROTOXICITY (Peripheral neuropathy) with almost NO BM suppression

vs

VinBLASTINE’s main AE is BM suppression…and its a potent vesicant:(

Question 6

which Inhibitors of the EGFR tyrosine kinase fits the following description:

• Colorectal cancer (efficacy is restricted to tumors expressing wild-type KRAS).

Answer 6

CETUXIMAB

Question 7

What is trastuzimab’s main AE?

Answer 7

CARDIOTOXICITY

Question 8

vats the difference between Cell cycle-specific drugs & Cell cycle-NON-specific drugs:

Answer 8

• Cell cycle-specific drugs:
Antineoplastic drugs that exert their action only on cells traversing the cell cycle.

Cell cycle-nonspecific drugs:

Can kill tumor cells whether they are cycling or resting in the G0 compartment. (Although cycling cells are more sensitive).

Question 9

Whats the difference between the route of Elimination of Irinotecan and Topotecan (these are Camptothecins) and both inhibir Topo 1

Answer 9

• Irinotecan and its metabolites are mainly eliminated in bile and feces, and dose reduction is required in case of liver dysfunction.
• For Topotecan: The main route of elimination is renal excretion and dosage must be adjusted in patients with renal impairment.

Question 10

do the following anticancer drugs have strong, moderate or mild MYELOSUPPRESSIVE EFFECTS

Cytarabine

Alkylating agents

Doxorubicin

Daunorubicin

Vinblastine

Answer 10

STRONG

Question 11

What are the 2 Nitrosoureas (Carmustine & Lomustine) used to treat mainly and why is this so. Lastly, which one is IV admin and which one is ORAL admin.

Answer 11

They are used to treat BRAIN TUMORS (primary or mets, including glioblastoma multiforme) bc they are EXTREMELY LIPOPHILIC AND CAN CROSS THE BBB

the -MUSTINES!

Carmustine (IV) & LOmustine (ORAL)

Question 12

• Some drugs have specific adverse effects:

• Doxorubicin causes…

• Cyclophosphamide & ifosphamide cause…

• Bleomycin causes…

cardiotoxicity.

pulmonary fibrosis.

hemorrhagic cystitis.

Answer 12

• Doxorubicin causes cardiotoxicity

D*_oxo CAUSES _*Dilated Cardiomyopathy

• Cyclophosphamide & ifosphamide cause hemorrhagic cystitis.
• Bleomycin causes pulmonary fibrosis.

Question 13

Erythema and desquamation of the skin observed at sites of prior radiation therapy “radiation recall reaction” is associated with what group of Antitumor antibiotics?

Answer 13

The Anthracyclines!

DOXOrubicin

DAUNOrubicin

(both non cell cycle specific)

Question 14

Which of the 4 Pyrimidine analogues are limited exclusively to hematologic malignancies, including acute myelogenous leukemia and non-Hodgkin’s lymphoma.

• Not active against solid tumors.

Answer 14

CYTARABINE (ARA-C) A deoxycytidine analogue

Question 15

Cisplatin and Carboplatin are both Platinum compounts. How do their AE profiles differ?

Answer 15

Cisplatin-maninly NEPHROTOXICITY

Carboplatin mainly BM SUPPRESION

[both dose limiting]

Question 16

How can Cisplatin’s main AE of NEPHROTOXICITY be helped?

Name 3 things that can be given

Answer 16

1. Pre-treatment hydration

2. Diuretics
3. Amifostine is a thiophosphate cytoprotective agent indicated to reduce the cumulative renal toxicity associated with repeated administration of cisplatin.

Question 17

is the following an example of primary or acquired resistance?

• No response to the drug on the first exposure.

Answer 17

PRIMARY RESISTANCE

Question 18

name that drug

• Stimulates natural killer cells to kill the transformed cells.
• Increases the expression of HLA molecules on tumor cells.

Clinical applications:

Kaposi sarcoma

Hairy cell leukemia

Renal cell carcinoma

Antiviral activity against HPV(condyloma acuminata),HBV and HCV.

Adverse effects:

• Flu like symptoms.

Answer 18

INTERFERON-a

Question 19

DOC for Non-small cell lung cancer.

Answer 19

GETFITINIB

Inhibitors of the EGFR tyrosine kinase

Question 20

Name that alkylation agent!

CNS depression (acute toxicity).

Leukopenia and thrombocytopenia.

Potent immunosuppressive agent.

Disulfiram-like reaction.

One metabolite is a weak monoamine oxidase (MAO) inhibitor

Carcinogenic potential is higher than that of most other alkylating agents (increased risk of secondary cancers in the form of acute leukemia).

Answer 20

PROCARBAZINE

Question 21

• Treatment-induced neoplasms are especially a problem after therapy with what group of anticancer drugs

Answer 21

alkylating agents.

Question 22

Amongst the Microtubule inhibitors (list them), VINCA ALKALOIDS (2) VS TAXANES (2)

what the main differentce in their MOA as it relates to their effect on the Mitotic spindle

Answer 22

VINCA ALKALOIDS: Vincristine, Vinblastine

TAXANES: Paclitaxel, Docetaxel

• Vinca alkaloids bindto β-tubulin. This disrupts assembly of microtubules. (VINCA ALKALOIDS BIND B TUBULIN AND INHIBIT ITS POLYMERIZATION INTO MICROTUBULES–> PREVENTS FORMATION OF MITOTIC SPINDLE–> M PHASE ARREST)

Taxanes promote microtubule polymerization and inhibit depolymerization (HYPERSTABILIZE POLYMERIZED MICROTUBULES IN THE M PHASE SO THE MITOTIC SPINDLE CANNOT BREAK DOWN–> ANANPHASE CANNOT OCCUR.

• Stabilization of the microtubules in a polymerized state arrests cells in mitosis and eventually leads to the activation of apoptosis.

Question 23

What is CISPLATINs MAIN AE?

Answer 23

NEPHROTOXICITY (dose-limiting)–> leading to electrolyte disturbances (hypoMG2+, hypo Ca2+, etc)

Question 24

The following drugs block DNA synthsis

Mix and match the drug with the action it has on DNA

Alkalating agents (cisplatin, busulfan, cyclophosphamide, Nitrosoureas (Carmustine, Lomustine)

Antitumor Antibiotics (Doxorubicin, Daunorubicin)

Etoposide & Teniposide

Antitumor Antibiotics (Bleomycin)

Irinotecan & Topotecan

Cross LInks DNA

are DNA intercalators

Inhibit topo II

Induces Breaks in DNA

Inhibits topi I

Answer 24

*Cross LInks DNA = Alkalating agents (eg: cisplatin)

*are DNA intercalators = Antitumor Antibiotics (Doxorubicin, Daunorubicin)

*Inhibit topo II = Etoposide & Teniposide

*Induces Breaks in DNA = Antitumor Antibiotics (Bleomycin)

*Inhibits topi I = Irinotecan & Topotecan

Question 25

does Raloxifene use lead to endometrial Hyperplasia? What is its effect on Osteoporosis and is it used in the treatment OR prevention of breast cancer?

Answer 25

1. NO it does NOT cause endometiral Hyperplasia 2. It is used to prevent and manage Osteoporosis due to its anabolic effects on bone 3. it PREVENTS doen NOT treat Breast cancer

Question 26

the **Hypersensitivity AE** of WHICH drug is reduced by premedication with **dexamethasone, diphenhydramine and an H2 blocker**

Answer 26

PACLITAXEL (taxane)-MT inhibitor

Question 27

What are L Asparaginases main 2 AE

Answer 27

1. Hemorrhage 2. Pancreatitis

Question 28

Mesna Leucovorin Dexrazoxane rescues bone marrow from methotrexate. reduces anthracycline-induced cardiotoxicity. reduces anthracycline-induced cardiotoxicity. mix&match.

Answer 28

Leucovorin **rescues bone marrow from methotrexate.** Mesna **reduces hemorrhagic cystitis caused by cyclophosphamide and ifosfamide.** Dexrazoxane **reduces anthracycline-induced cardiotoxicity.**

Question 29

* \_\_\_\_\_\_\_\_ is N5-formyl-THF. * its an Antidote to drugs that decrease levels of folic acid, such as methotrexate, to rescue the bone marrow. * It provides the normal tissues with the reduced folate, thus circumventing the inhibition of DHFR.

Answer 29

Leucovorin

Question 30

**Filgrastim** reverses\_\_\_\_\_\_\_\_caused by many anticancer agents. **Amifostine** is a cytoprotective agent that reduces renal toxicity caused by....

Answer 30

**neutropenia** **cisplatin**

Question 31

Name that drug: Its an antimetablite **DOC for Colorectal Cancer** One of its classic AE is "**Hand/foot" Syndrome** what happens when you give Leucovorin with it? what enzyme is it catabolized by?

Answer 31

**5FU (pyrimidine analogue) & Capecitabine** (both Uracil analogues-Pyrimidine Analogues) ## Footnote If you give **Leucovorin** with it, its **enhances the cytotoxic effects** (which is favorable for an anticancer drug) • Is mainly catabolized by the enzyme **Dihydropyrimidine dehydrogenase (DPD).**

Question 32

**Amifostine** is combined with what alkylating agent in order to reduce its AE which include OTOTOXICITY, NEPHROTOXICITY, NEUROTOXICITY **Oxaliplatin** could be combined with what drug (in same class as the one alluded to above)

Answer 32

**CISPLATIN + AMIFOSTINE** (free radical scavenger) **CARBOPLATIN + OXALIPLATIN**

Question 33

If a patient has **Tamoxifen resistant breast cancer** whats and alternative?

Answer 33

**FULVESTRAN**T a SERD (downregulator) • **Pure estrogen receptor antagonist** with no agonist activity. * Increases ER degradation. * Reduces the number of ER molecules in cells.

Question 34

do the following anticancer drugs have strong, moderate or mild MYELOSUPPRESSIVE EFFECTS Carboplatin Methotrexate 5-FU

Answer 34

MODERATE

Question 35

list the drugs that are **potent Vesicants** (3 specific ones)

Answer 35

**Vinblastine (vinca alkaloid** in the broad class of **MIcrotubule inhibitors)** Alkalating agens **MECHLORETHAMINE** (a **Nitrogen mustard** in the broad clas of **Alkalating agents**) **DACARBAZINE** (DTIC) (the only **Triazine** in the broad clas of **Alkalating agents**)

Question 36

List cytotoxic drugs that, unlike most cytotoxic durgs, simply cause Mild-mod BM suppression

Answer 36

**Dacarbazine-(Triazine)-Alkylating agent-**its too busy being a *potent Vesicant!* **CIsplatin (Platinum Analogue)-Alkylating agent -**its too busy causing *Nephrotoxicity*--\> leading to electrolyte disturbances and *OTOtoxicity* **Vincristine** (**MT inhibitor**)-its too busy causing AE like *Peripheral Neuropathy* bc of its Neurotoxic effects **Bleomycin (Antitumor Ab**)-its too busy causing AE in tissues with decreased hydrolase activity like *Lung and Skin.*

Question 37

TRASTUZUMAB AE = ?

Answer 37

**Cardiotoxicity.** TRASTUZUMAB is Humanized Monoclonal antibody against ErbB2 (HER2).

Question 38

do the following anticancer drugs have strong, moderate or mild MYELOSUPPRESSIVE EFFECTS Bleomycin Vincristine Asparaginase

Answer 38

MILD

Question 39

PROTEASOME inhibitors

Answer 39

BORTEZOMIB * Proteasome Inhibitor. * Induces growth inhibition and apoptosis of tumor cells. **Clinical applications:** * Multiple myeloma. * Mantle cell lymphoma.

Question 40

• _First-line treatment_ of **metastatic colorectal cancer.** this med is activated by a three-steps enzymatic conversion to 5-FU. The **first two steps** occur in the **liver .** The **last step** ***_occurs in the tumor_*** and it is catalyzed by the enzyme **Thymidine phosphorylase.**

Answer 40

**CAPECITABINE**