CHEMOTHERAPEUTIC DRUGS

Question 1

Cytarabine (arabinofuranosyl cytidine)

Answer 1

Mechanism:
Incorporation of pyrimidine analog into DNA→ ↓ DNA synthesis (via termination of DNA chain)
At higher concentrations, inhibits DNA polymerase.
S-phase specific

Clinical Use:
Leukemias (especially AML), lymphomas

Adverse Effects:
Myelosuppression (pancytopenia)
Megaloblastic anemia
Hepatotoxicity
Pancreatitis
Sudden respiratory distress syndrome
Neurotoxicity (e.g., seizures, cerebellar toxicity)

Question 2

Pemetrexed

Answer 2

Mechanism:
Multitargeted antifolate (pemetrexed inhibits dihydrofolate reductase, thymidylate synthase, glycineamide ribonucleotide formyltransferase, and, potentially, other enzymes involved in folate metabolism)
Inhibition of thymidylate synthase → ↓ synthesis of deoxythymidine monophosphate (dTMP) → ↓ DNA and RNA synthesis

Clinical Use:
Pleural mesothelioma
NSCLC
Ovarian cancer

Adverse Effects:
Alopecia
Erythematous, pruritic rash (pemetrexed)
Desquamation
Anemia
Pharyngitis
GI symptoms (e.g, diarrhea)

Question 3

5-Fluorouracil (5-FU)

Answer 3

Mechanism:
Activation of 5-fluorouracil to 5-FdUMP
Complex formation with thymidylate synthase and folic acid → inhibition of thymidylate synthase → ↓ dTMP production → ↓ DNA synthesis
Incorporation of pyrimidine analog into DNA and RNA → ↓ DNA and RNA synthesis
Leucovorin enhances antineoplastic efficacy of 5-fluorouracil

Clinical Use:
Systemic treatment
-Breast cancer
-Gastric cancer
-Colorectal cancer
-Pancreatic cancer
Topical treatment
-Actinic keratosis
-Basal cell carcinoma

Adverse Effects:
Myelosuppression
Palmar-plantar erythrodysesthesia (hand-foot syndrome)
Cardiotoxicity
GI symptoms (e.g. nausea, diarrhea, mucosal ulcerations)
Higher toxicity in patients with dihydropyrimidine dehydrogenase deficiency
Hepatotoxicity
Hyperammonemic encephalopathy

Question 4

Capecitabine

Answer 4

Prodrug for 5-FU

Mechanism:
Activation of 5-fluorouracil to 5-FdUMP
Complex formation with thymidylate synthase and folic acid → inhibition of
thymidylate synthase → ↓ dTMP production → ↓ DNA synthesis
Incorporation of pyrimidine analog into DNA and RNA → ↓ DNA and RNA synthesis
Leucovorin enhances antineoplastic efficacy of 5-fluorouracil

Clinical Use:
Myelosuppression
Palmar-plantar erythrodysesthesia (hand-foot syndrome)
Cardiotoxicity
GI symptoms (e.g. nausea, diarrhea, mucosal ulcerations)
Higher toxicity in patients with dihydropyrimidine dehydrogenase deficiency
Hepatotoxicity
Hyperammonemic encephalopathy

Adverse Effects:
Systemic treatment
-Breast cancer
-Gastric cancer
-Colorectal cancer
-Pancreatic cancer
Topical treatment
-Actinic keratosis
-Basal cell carcinoma

Question 5

Gemcitabine

Answer 5

Mechanism:
Incorporation of pyrimidine analog into DNA → ↓ DNA synthesis

Clinical Use:
Breast cancer
NSCLC
Ovarian cancer
Pancreatic cancer

Adverse Effects:
Myelosuppression
Capillary leak syndrome
Hemolytic uremic syndrome
Pulmonary toxicity
Hepatotoxicity

Question 6

Azathioprine

Answer 6

Prodrug for 6-MP

Mechanism:
6-Mercaptopurine is converted into the active metabolite by hypoxanthine-guanine phosphoribosyltransferase (HGPRT) → ↓ de novo synthesis of purines
Incorporation of purine analog (thiol analog) into DNA → ↓ DNA synthesis

Clinical Use:
Acute lymphoblastic leukemia
Non-neoplastic conditions: immunosuppression
Prevention of organ transplant rejection
Treatment of autoimmune diseases
For example, inflammatory bowel disease, systemic lupus erythematosus, rheumatoid arthritis
Used in patients with steroid-resistance or to reduce steroid dose

Adverse Effects:
Myelosuppression
GI symptoms (e.g., CINV, diarrhea)
Hepatotoxicity
Secondary malignancy (cases of AML have been reported after prolonged administration of 6-MP in the therapy of Crohn disease)
Metabolized by xanthine oxidase; therefore, toxicity increases with concurrent use of allopurinol and/or febuxostat

Question 7

Fludarabine

Answer 7

Mechanism:
Incorporation of purine analog into DNA → ↓ DNA and RNA synthesis

Clinical Use:
CLL
Low-grade lymphomas (e.g., follicular B-cell lymphoma)
Myeloablation prior to hematopoietic stem cell transplant

Adverse Effects:
Autoimmune effects (e.g., autoimmune hemolytic anemia, idiopathic thrombocytopenia)
Myelosuppression
Neurotoxicity

Question 8

Cladribine

Answer 8

Mechanism:
Incorporation of purine analog into DNA → breakage of DNA strand → ↓ DNA synthesis
Inhibits DNA polymerase
Selectively toxic to lymphocytes and monocytes that have a high deoxycytidine kinase and a low deoxynucleotidase content.
Deoxycytidine kinase phosphorylates cladribine (low deoxynucleotidase content prevents dephosphorylation)
Monophosphorylated cladribine is resistant to adenosine deaminase and accumulates within the cells.

Clinical Use:
Hairy cell leukemia
CLL
Low-grade lymphomas
Nonneoplastic conditions: multiple sclerosis

Adverse Effects:
Myelosuppression
Headache
Nephrotoxicity
Neurotoxicity
Cardiotoxicity
Hepatotoxicity

Question 9

Hydroxyurea (hydroxycarbamide)

Answer 9

Mechanism:
Inhibition of ribonucleotide reductase → ↓ DNA replication (S phase) → massive cytoreduction
Increases production of hemoglobin F (HbF)

Clinical Use:
Myoproliferative disorders
Chronic myeloid leukemia
Polycythemia vera
Essential thrombocythemia
Leukostasis syndrome
Head and neck cancer
Sickle cell crisis prophylaxis

Adverse Effects:
Myelosuppression
Macrocytosis, megaloblastic anemia
Secondary malignancy
Birth defects
Pulmonary toxicity

Question 10

Cyclophosphamide

Answer 10

Alkylating agent

Mechanism:
Alkylation of DNA/RNA → cross-links DNA at guanine N–7 → ↓ DNA replication
Cyclophosphamide and ifosfamide require activation in the liver.

Clinical Use:
Malignancies
-Solid tumors (e.g., breast cancer, ovarian cancer, small cell lung cancer)
-Leukemias
-Lymphomas
-Multiple myeloma
Nonneoplastic conditions
-Autoimmune diseases (e.g., systemic lupus erythematosus, granulomatosis with polyangiitis)
-Nephrotic syndrome

Adverse Effects:
Bladder toxicity
-Hemorrhagic cystitis (inflammation of the bladder, damaging to the epithelium and blood vessels; bladder carcinoma)
Myelosuppression
Syndrome of inappropriate antidiuretic hormone secretion (SIADH)
Pulmonary toxicity
Cardiac toxicity
Infertility

Mesna (2-MErcaptoethane Sulfonate Na) and fluids prevent bladder toxicity (sulfate group of mesna binds toxic metabolites)

Question 11

Ifosfamide

Answer 11

Alkylating agent

Mechanism:
Alkylation of DNA/RNA → cross-links DNA at guanine N–7 → ↓ DNA replication
Cyclophosphamide and ifosfamide require activation in the liver.

Clinical Use:
Solid tumors (e.g., testicular germ-cell cancer, osteosarcoma) 

Adverse Effects:
Bladder toxicity
-Hemorrhagic cystitis (inflammation of the bladder, damaging to the epithelium and blood vessels; bladder carcinoma)
Myelosuppression
Syndrome of inappropriate antidiuretic hormone secretion (SIADH)
Pulmonary toxicity
Cardiac toxicity
Infertility
Fanconi syndrome (ifosfamide)
Neurotoxicity (ifosfamide)

Mesna (2-MErcaptoethane Sulfonate Na) and fluids prevent bladder toxicity (sulfate group of mesna binds toxic metabolites)

Question 12

Chlorambucil

Answer 12

Alkylating agent
Nitrogen mustard

Mechanism:
Alkylation of DNA/RNA → cross-links DNA at guanine N–7 → ↓ DNA replication
Cyclophosphamide and ifosfamide require activation in the liver.

Clinical Use:
Chronic lymphocytic leukemia
Hodgkin lymphoma
Non-Hodgkin lymphoma

Adverse Effects:
Myelosuppression
Oral ulcerations
GI symptoms (e.g., CINV)
Pulmonary fibrosis
Infertility

Question 13

Melphalan

Answer 13

Alkylating agent
Nitrogen mustard

Mechanism:
Alkylation of DNA/RNA → cross-links DNA at guanine N–7 → ↓ DNA replication
Cyclophosphamide and ifosfamide require activation in the liver.

Clinical Use:
Multiple myeloma
Ovarian cancer
Amyloidosis

Adverse Effects:
Myelosuppression
Pulmonary toxicity
Hypokalemia
Peripheral edema
Secondary leukemia

Question 14

Temozolomide

Answer 14

Alkylating agent

Mechanism:
Alkylation of DNA/RNA → cross-links DNA at guanine N–7 → ↓ DNA replication
Cyclophosphamide and ifosfamide require activation in the liver.

Clinical Use:
Glioblastoma
Anaplastic astrocytoma

Adverse Effects:
Myelosuppression
Neurotoxicity
Pneumocystis pneumonia

Question 15

Carmustine

Answer 15

Alkylating agent
Nitrosourea

Mechanism:
Alkylation of DNA/RNA → cross-links between DNA → ↓ DNA synthesis
Require bioactivation
Due to their high lipophilicity, carmustine and lomustine can cross the blood-brain barrier and act in the CNS.

Clinical Use:
Brain tumors (e.g., glioblastoma multiforme)
Multiple myeloma (carmustine, lomustine)
Hodgkin lymphoma

Adverse Effects:
Neurotoxicity (e.g., convulsions, dizziness, ataxia)
Myelosuppression
Pulmonary toxicity
Secondary leukemia

Question 16

Lomustine

Answer 16

Alkylating agent
Nitrosourea

Mechanism:
Alkylation of DNA/RNA → cross-links between DNA → ↓ DNA synthesis
Require bioactivation
Due to their high lipophilicity, carmustine and lomustine can cross the blood-brain barrier and act in the CNS.

Clinical Use:
Brain tumors (e.g., glioblastoma multiforme)
Multiple myeloma (carmustine, lomustine)
Hodgkin lymphoma

Adverse Effects:
Neurotoxicity (e.g., convulsions, dizziness, ataxia)
Myelosuppression
Pulmonary toxicity
Secondary leukemia

Question 17

Streptozocin

Answer 17

Alkylating agent
Nitrosourea

Mechanism:
Alkylation of DNA/RNA → cross-links between DNA → ↓ DNA synthesis
Require bioactivation
Do not cross the blood-brain barrier

Clinical Use:
Hodgkin lymphoma
Pancreatic neuroendocrine tumors (streptozocin)

Adverse Effects:
Neurotoxicity (e.g., convulsions, dizziness, ataxia)
Myelosuppression
Pulmonary toxicity
Secondary leukemia

Question 18

Busulfan

Answer 18

Alkylating agent

Mechanism:
Cross-links between DNA strands → ↓ DNA replication

Clinical Use:
Myeloablation prior to hematopoietic stem cell transplantation
CML

Adverse Effects:
Severe myelosuppression (expected effect)
Pulmonary fibrosis
Hyperpigmentation
Electrolyte imbalance
Cardiotoxicity
Hepatotoxicity
Neurotoxicity (e.g., convulsions)

Question 19

Procarbazine

Answer 19

Alkylating agent

Mechanism:
Mechanism of action is not fully understood
Inhibition of transmethylation of methionine into transfer RNA → ↓ DNA, RNA, and protein synthesis
Also acts as a weak MAO inhibitor

Clinical Use:
Hodgkin lymphoma
Brain tumors (e.g., gliomas)

Adverse Effects:
Myelosuppression
Pulmonary toxicity
Secondary leukemia
Disulfiram-like reaction
Tyramine crisis
Gonadal damage

Question 20

Cisplatin

Answer 20

Alkylating agent
Platinum-based agent

Mechanism:
Cross-links between DNA strands → ↓ DNA replication

Clinical Use:
Lymphomas
Solid tumors
-Bladder cancer (cisplatin)
-Testicular cancer (cisplatin)
-Ovarian cancer (cisplatin, carboplatin)
-Lung cancer (cisplatin, carboplatin)
-Cervical cancer (cisplatin)
-Osteosarcoma (cisplatin)

Adverse Effects:
Myelosuppression
Nephrotoxicity (may manifest as Fanconi syndrome)
Neurotoxicity (including peripheral neuropathies)
Ototoxicity
Chemotherapy induced nausea and vomiting

Prevent nephrotoxicity (may manifest as Fanconi syndrome) with:

• Amifostine (free radical scavenger)
• IV saline (induces chloride diuresis → ↑ urine chloride concentration → ↓ cisplatin reactivity)

Question 21

Carboplatin

Answer 21

Alkylating agent
Platinum-based agent

Mechanism:
Cross-links between DNA strands → ↓ DNA replication

Clinical Use:
Lymphomas
Solid tumors
-Ovarian cancer (cisplatin, carboplatin)
-Lung cancer (cisplatin, carboplatin)

Adverse Effects:
Myelosuppression
Nephrotoxicity (may manifest as Fanconi syndrome)
Neurotoxicity (including peripheral neuropathies)
Ototoxicity
Chemotherapy induced nausea and vomiting

Prevent nephrotoxicity (may manifest as Fanconi syndrome) with:

• Amifostine (free radical scavenger)
• IV saline (induces chloride diuresis → ↑ urine chloride concentration → ↓ cisplatin reactivity)

Question 22

Oxaliplatin

Answer 22

Alkylating agent
Platinum-based agent

Mechanism:
Cross-links between DNA strands → ↓ DNA replication

Clinical Use:
Lymphomas
Solid tumors
-Colorectal cancer (oxaliplatin)

Adverse Effects:
Myelosuppression
Nephrotoxicity (may manifest as Fanconi syndrome)
Neurotoxicity (including peripheral neuropathies)
Ototoxicity
Chemotherapy induced nausea and vomiting

Prevent nephrotoxicity (may manifest as Fanconi syndrome) with:

• Amifostine (free radical scavenger)
• IV saline (induces chloride diuresis → ↑ urine chloride concentration → ↓ cisplatin reactivity)

Question 23

Irinotecan

Answer 23

Topoisomerase inhibitor

Mechanism:
Inhibition of topoisomerase I → ↓ DNA unwinding → ↓ DNA replication and DNA degradation (because of ssDNA breaks)

Clinical Use:
Colorectal cancer
Small-cell lung cancer
Pancreatic cancer

Adverse Effects:
Myelosuppression
GI symptoms (e.g., diarrhea)
Cholinergic syndrome
Alopecia
Pulmonary toxicity (irinotecan)

Question 24

Topotecan

Answer 24

Topoisomerase inhibitor

Mechanism:
Inhibition of topoisomerase I → ↓ DNA unwinding → ↓ DNA replication and DNA degradation (because of ssDNA breaks)

Clinical Use:
Cervical cancer
Ovarian cancer
Small-cell lung cancer

Adverse Effects:
Myelosuppression
GI symptoms (e.g., diarrhea)
Cholinergic syndrome
Alopecia

Question 25

Etoposide

Answer 25

Topoisomerase inhibitor Mechanism: Inhibition of topoisomerase II → ↑ DNA degradation (dsDNA breaks) and ↓ DNA replication (cell cycle arrest in S and G2 phase) ``` Clinical Use: Solid tumors Testicular cancer Small-cell lung cancer Leukemias Lymphomas ``` ``` Adverse Effects: Myelosuppression Alopecia Hypotension Mucositis (teniposide) ```

Question 26

Vincristine

Answer 26

Mitotic Inhibitor Vinca alkaloid Mechanism: Binding of β-tubulin → inhibition of β-tubulin polymerization into microtubules → prevention of mitotic spindle formation → mitotic arrest of the cell in metaphase (M-phase) ``` Clinical Use: Solid tumors -Neuroblastoma -Rhabdomyosarcoma -Wilms tumor Other -Acute lymphocytic leukemia -Hodgkin lymphoma -NHL ``` Adverse Effects: Neurotoxicity (e.g., areflexia, peripheral neuropathy) Paralytic ileus, constipation Extravasation can cause significant irritation and/or ulceration of local tissue Acute bronchospasm Uric acid nephropathy

Question 27

Vinblastine

Answer 27

Mitotic Inhibitor Vinca alkaloid Mechanism: Binding of β-tubulin → inhibition of β-tubulin polymerization into microtubules→ prevention of mitotic spindle formation → mitotic arrest of the cell in metaphase (M-phase) ``` Clinical Use: Solid tumors Kaposi sarcoma Langerhans cell histiocytosis Testicular cancer Other Hodgkin lymphoma NHL ``` Adverse Effects: Myelosuppression Extravasation can cause significant irritation of local tissue Pulmonary toxicity

Question 28

Vinorelbine

Answer 28

Mitotic Inhibitor Vinca alkaloid Mechanism: Binding of β-tubulin → inhibition of β-tubulin polymerization into microtubules→ prevention of mitotic spindle formation → mitotic arrest of the cell in metaphase (M-phase) Clinical Use: Non-small cell lung cancer Breast cancer Adverse Effects: Myelosuppression Hypersensitivity reactions

Question 29

Docetaxel

Answer 29

Mitotic Inhibitor Taxanes Mechanism: Hyperstabilization of polymerized microtubules → ↓ mitotic spindles breakdown → mitotic arrest in metaphase (not proceeding to anaphase) ``` Clinical Use: Breast cancer Ovarian cancer Prostate cancer Gastric cancer Kaposi sarcoma Non-small cell lung cancer ``` ``` Adverse Effects: Myelosuppression Neuropathy Hepatotoxicity Hypersensitivity reactions Fluid retention Nail changes (e.g., nail bed purpura, onycholysis, nail pigmentation, splinter hemorrhage, subungual abscess) ```

Question 30

Paclitaxel

Answer 30

Mitotic Inhibitor Taxanes Mechanism: Hyperstabilization of polymerized microtubules → ↓ mitotic spindles breakdown → mitotic arrest in metaphase (not proceeding to anaphase) ``` Clinical Use: Breast cancer Ovarian cancer Prostate cancer Gastric cancer Kaposi sarcoma Non-small cell lung cancer ``` ``` Adverse Effects: Myelosuppression Neuropathy Hepatotoxicity Hypersensitivity reactions Fluid retention Nail changes (e.g., nail bed purpura, onycholysis, nail pigmentation, splinter hemorrhage, subungual abscess) ```

Question 31

Eribulin

Answer 31

Mitotic Inhibitor Nontaxane microtubule inhibitor Mechanism: Inhibition of mitotic spindle formation → mitotic blockage → cell cycle arrest at the G2/M phase Clinical Use: Breast cancer Liposarcoma Adverse Effects: Myelosuppression Peripheral neuropathy QT prolongation

Question 32

Ixabepilone

Answer 32

Mitotic Inhibitor Nontaxane microtubule inhibitor Mechanism: Binding to β-tubulin → hyperstabilization of the microtubules → ↓ breakdown of mitotic spindles breakdown → mitotic arrest in metaphase Clinical Use: Breast cancer Adverse Effects: Hypersensitivity Myelosuppression Peripheral neuropathy

Question 33

Epothilone

Answer 33

Mitotic Inhibitor Nontaxane microtubule inhibitor Mechanism: Binding to β-tubulin → hyperstabilization of the microtubules → ↓ breakdown of mitotic spindles breakdown → mitotic arrest in metaphase Clinical Use: Breast cancer Adverse Effects: Hypersensitivity Myelosuppression Peripheral neuropathy

Question 34

Bleomycin

Answer 34

Mechanism: Induces formation of free radicals → breakage of DNA strand → cell cycle arrest at G2 phase ``` Clinical Use: Squamous cell carcinomas of the head and neck Testicular cancer Hodgkin lymphoma Malignant pleural effusion ``` ``` Adverse Effects: Pulmonary fibrosis Hyperpigmentation of the skin Mucositis Alopecia Minimal myelosuppression Idiosyncratic reaction ```

Question 35

Actinomycin D (dactinomycin)

Answer 35

Mechanism: DNA intercalation → interference with DNA transcription → ↓ RNA synthesis ``` Clinical Use: Childhood tumors -Wilms tumor -Ewing sarcoma -Rhabdomyosarcoma Gestational trophoblastic neoplasia ``` ``` Adverse Effects: Myelosuppression Mucocutaneous toxicity Nephrotoxicity Hepatotoxicity ```

Question 36

Doxorubicin

Answer 36

Anthracyclines are classically classified as cytotoxic antibiotics, but in terms of their chemotherapeutic action, they could also be classed as topoisomerase inhibitors. Mechanism: Inhibition of topoisomerase II → ↑ DNA degradation (dsDNA breaks) and ↓ DNA replication Formation of free radicals → breakage of DNA strands DNA intercalation → breakage of DNA strands and ↓ DNA replication ``` Clinical Use: Breast cancer (doxorubicin) Metastatic solid tumors (doxorubicin) Lymphomas (doxorubicin) Kaposi sarcoma (doxorubicin) Osteosarcoma ``` ``` Adverse Effects: Cardiotoxicity (dilated cardiomyopathy with systolic CHF) Myelosuppression Alopecia Extravasation Infertility Urine discoloration ``` Prevent cardiotoxicity with dexrazoxane (iron chelating agent)

Question 37

Mitomycin

Answer 37

Mechanism: Cross-linking between DNA strands → ↓ DNA and RNA synthesis Clinical Use: Palliative chemotherapy of gastric and pancreatic cancer Bladder cancer ``` Adverse Effects: Myelosuppression Hemolytic uremic syndrome Heart failure Thrombotic thrombocytopenic purpura Bladder fibrosis (with intravesical administration) ARDS ```

Question 38

Imatinib

Answer 38

BCR-ABL and c-KIT tyrosine kinase inhibitors Mechanism: Inhibition of autophosphorylation and activation of multiple proteins by tyrosine kinases (e.g.,BCR-ABL, c-KIT) Clinical Use: Chronic myeloid leukemia BCR-ABL positive ALL Kit (CD117)-positive gastrointestinal stromal tumors Aggressive systemic mastocytosis (imatinib) Dermatofibrosarcoma protuberans (imatinib) Hypereosinophilic syndrome (imatinib) Chronic eosinophilic leukemia (imatinib) Myelodysplastic/Myeloproliferative diseases (imatinib) ``` Adverse Effects: Fluid retention and edema Myelosuppression Hepatotoxicity (e.g., ↑ LFTs) Myalgia Neurotoxicity Bullous dermatologic reactions Hemorrhage Nephrotoxicity ```

Question 39

Dasatinib

Answer 39

BCR-ABL and c-KIT tyrosine kinase inhibitors Mechanism: Inhibition of autophosphorylation and activation of multiple proteins by tyrosine kinases (e.g.,BCR-ABL, c-KIT) Clinical Use: Chronic myeloid leukemia BCR-ABL positive ALL Kit (CD117)-positive gastrointestinal stromal tumors ``` Adverse Effects: Fluid retention and edema Myelosuppression Hepatotoxicity (e.g., ↑ LFTs) Myalgia Cardiotoxicity Skin rash Hemorrhage Pulmonary arterial hypertension QT prolongation ```

Question 40

Nilotinib

Answer 40

BCR-ABL and c-KIT tyrosine kinase inhibitors Mechanism: Inhibition of autophosphorylation and activation of multiple proteins by tyrosine kinases (e.g.,BCR-ABL, c-KIT) Clinical Use: Chronic myeloid leukemia BCR-ABL positive ALL Kit (CD117)-positive gastrointestinal stromal tumors ``` Adverse Effects: Fluid retention and edema Myelosuppression Hepatotoxicity (e.g., ↑ LFTs) Myalgia ```

Question 41

Erlotinib

Answer 41

EGFR tyrosine kinase inhibitors Mechanism: Inhibition of HER1/EGFR tyrosine kinase → blockage of intracellular phosphorylation → cell death Clinical Use: Non-small cell lung cancer Pancreatic cancer ``` Adverse Effects: Dermatologic toxicity (e.g., rash, bullous, blistering, and exfoliating skin conditions) Fatigue GI toxicity (e.g., diarrhea) Hepatotoxicity Ocular toxicity Nephrotoxicity ```

Question 42

Gefitinib

Answer 42

EGFR tyrosine kinase inhibitors Mechanism: Inhibition of HER1/EGFR tyrosine kinase → blockage of intracellular phosphorylation → cell death Clinical Use: Non-small cell lung cancer Pancreatic cancer ``` Adverse Effects: Dermatologic toxicity (e.g., rash, bullous, blistering, and exfoliating skin conditions) Fatigue GI toxicity (e.g., diarrhea) Hepatotoxicity Ocular toxicity Nephrotoxicity ```

Question 43

Afatinib

Answer 43

EGFR tyrosine kinase inhibitors Mechanism: Inhibition of HER1/EGFR tyrosine kinase → blockage of intracellular phosphorylation → cell death Clinical Use: Non-small cell lung cancer Pancreatic cancer ``` Adverse Effects: Dermatologic toxicity (e.g., rash, bullous, blistering, and exfoliating skin conditions) Fatigue GI toxicity (e.g., diarrhea) Hepatotoxicity Ocular toxicity Nephrotoxicity ```

Question 44

Osimertinib

Answer 44

EGFR tyrosine kinase inhibitors Mechanism: Inhibition of HER1/EGFR tyrosine kinase → blockage of intracellular phosphorylation → cell death Clinical Use: Non-small cell lung cancer Pancreatic cancer ``` Adverse Effects: Dermatologic toxicity (e.g., rash, bullous, blistering, and exfoliating skin conditions) Fatigue GI toxicity (e.g., diarrhea) Hepatotoxicity Ocular toxicity Nephrotoxicity ```

Question 45

Alectinib

Answer 45

ALK tyrosine kinase inhibitors Mechanism: Inhibition of the anaplastic lymphoma kinase Clinical Use: Non-small cell lung cancer ``` Adverse Effects: GI toxicity (e.g., diarrhea) Fluid retention and edema Dermatologic toxicity (e.g., rash) Ocular toxicity Neurotoxicity Hepatotoxicity ```

Question 46

Crizotinib

Answer 46

ALK tyrosine kinase inhibitors Mechanism: Inhibition of the anaplastic lymphoma kinase Clinical Use: Non-small cell lung cancer ``` Adverse Effects: GI toxicity (e.g., diarrhea) Fluid retention and edema Dermatologic toxicity (e.g., rash) Ocular toxicity Neurotoxicity Hepatotoxicity ```

Question 47

Vemurafenib

Answer 47

V600E mutated-BRAF oncogene inhibitors Mechanism: Selective inhibition of BRAF oncogene with V600E mutation → inhibition of cancer cell growth Often administered with MEK inhibitors (e.g., trametinib) Clinical Use: Metastatic melanoma Erdheim-Chester disease ``` Adverse Effects: Dermatologic toxicity (e.g., rash) GI toxicity (e.g., nausea, diarrhea) Fatigue QT prolongation Dupuytren contracture and plantar fascial fibromatosis Pancreatitis ```

Question 48

Trametinib

Answer 48

MEK inhibitor Mechanism: Inhibition of MAP kinase signaling pathway → inhibition of cancer cell growth and induction of apoptosis Clinical Use: Non-small cell lung cancer Melanoma Adverse Effects: Hepatotoxicity Dermatologic toxicity GI toxicity

Question 49

Ibrutinib

Answer 49

Bruton kinase inhibitor Mechanism: Inhibition of Bruton tyrosine kinase (BTK) → growth inhibition of malignant B cells ``` Clinical Use: Chronic lymphocytic leukemia (CLL) Mantle cell lymphoma Waldenstrom macroglobulinemia Graft-versus-host disease ``` Adverse Effects: GI toxicity Cardiotoxicity (e.g., atrial fibrillation) Hepatotoxicity

Question 50

Ruxolitinib

Answer 50

Janus kinase inhibitor Mechanism: Inhibition of JAK1 and JAK2 kinase → reduced activation of hematopoietic progenitor cells Clinical Use: Polycythemia vera Myelofibrosis Adverse Effects: Hepatotoxicity (e.g., ↑ LFTs) Hematologic toxicity (e.g., thrombocytopenia, anemia)

Question 51

Palbociclib

Answer 51

CDK inhibitor Mechanism: Inhibition of cyclin-dependent kinase 4 and 6 → inhibition of cancer cell growth and induction of apoptosis Clinical Use: Metastatic breast cancer Adverse Effects: Myelosuppression Pulmonary toxicity (e.g., pneumonitis)

Question 52

L-asparaginase

Answer 52

Mechanism: Cleavage of the amino acid L-asparagine by L-asparaginase → ↓ asparagine source for leukemic cells → cytotoxicity specific to leukemic cells Cells in acute lymphoblastic leukemia and certain other cancer cells (e.g., lymphoblastic lymphoma, AML) are unable to synthesize asparagine on their own. This agent breaks down circulating asparagine, thus depriving cells of it. Clinical Use: Acute lymphoblastic leukemia ``` Adverse Effects: Hepatotoxicity Pancreatitis Hypofibrinogenemia and bleeding Thrombosis Hyperglycemia Allergic reactions ```

Question 53

Bortezomib

Answer 53

Proteasome inhibitor Mechanism: Inhibition of ubiquitinated apoptotic protein degradation (e.g., of p53) → arrest in G2/M → programmed cell death (apoptosis) Clinical Use: Mantle cell lymphoma (bortezomib) Multiple myeloma ``` Adverse Effects: Peripheral neuropathy Herpes zoster reactivation Hepatotoxicity Thrombocytopenia Neutropenia Pulmonary toxicity Heart failure ```

Question 54

Carfilzomib

Answer 54

Proteasome inhibitor Mechanism: Inhibition of ubiquitinated apoptotic protein degradation (e.g., of p53) → arrest in G2/M → programmed cell death (apoptosis) Clinical Use: Multiple myeloma ``` Adverse Effects: Peripheral neuropathy Herpes zoster reactivation Hepatotoxicity Thrombocytopenia Neutropenia Pulmonary toxicity Heart failure ```

Question 55

Ixazomib

Answer 55

Proteasome inhibitor Mechanism: Inhibition of ubiquitinated apoptotic protein degradation (e.g., of p53) → arrest in G2/M → programmed cell death (apoptosis) Clinical Use: Multiple myeloma ``` Adverse Effects: Peripheral neuropathy Herpes zoster reactivation Hepatotoxicity Thrombocytopenia Neutropenia Pulmonary toxicity Heart failure ```

Question 56

Olaparib

Answer 56

PARP Inhibitor Mechanism: Inhibition of poly (ADP-ribose) polymerase → ↓ repair of single-strand DNA breaks ``` Clinical Use: Breast cancer Ovarian cancer Prostate cancer Pancreatic cancer ``` Adverse Effects: Myelosuppression Fluid retention and edema GI toxicity (e.g., diarrhea)

Question 57

Daunorubicin

Answer 57

Anthracyclines are classically classified as cytotoxic antibiotics, but in terms of their chemotherapeutic action, they could also be classed as topoisomerase inhibitors. Mechanism: Inhibition of topoisomerase II → ↑ DNA degradation (dsDNA breaks) and ↓ DNA replication Formation of free radicals → breakage of DNA strands DNA intercalation → breakage of DNA strands and ↓ DNA replication Clinical Use: Leukemias (daunorubicin, idarubicin) Osteosarcoma ``` Adverse Effects: Cardiotoxicity (dilated cardiomyopathy with systolic CHF) Myelosuppression Alopecia Extravasation Infertility Urine discoloration ```

Question 58

Idarubicin

Answer 58

Anthracyclines are classically classified as cytotoxic antibiotics, but in terms of their chemotherapeutic action, they could also be classed as topoisomerase inhibitors. Mechanism: Inhibition of topoisomerase II → ↑ DNA degradation (dsDNA breaks) and ↓ DNA replication Formation of free radicals → breakage of DNA strands DNA intercalation → breakage of DNA strands and ↓ DNA replication Clinical Use: Leukemias (daunorubicin, idarubicin) Osteosarcoma ``` Adverse Effects: Cardiotoxicity (dilated cardiomyopathy with systolic CHF) Myelosuppression Alopecia Extravasation Infertility Urine discoloration ```

Question 59

Dabrafenib

Answer 59

V600E mutated-BRAF oncogene inhibitors Mechanism: Selective inhibition of BRAF oncogene with V600E mutation → inhibition of cancer cell growth Often administered with MEK inhibitors (e.g., trametinib) Clinical Use: Metastatic melanoma Non-small cell lung cancer Thyroid cancer ``` Adverse Effects: Dermatologic toxicity (e.g., rash) GI toxicity (e.g., nausea, diarrhea) Fatigue QT prolongation For dabrafenib and encorafenib Cardiomyopathy Febrile reactions Hyperglycemia Venous thromboembolism ```

Question 60

Encorafenib

Answer 60

V600E mutated-BRAF oncogene inhibitors Mechanism: Selective inhibition of BRAF oncogene with V600E mutation → inhibition of cancer cell growth Often administered with MEK inhibitors (e.g., trametinib) Clinical Use: Metastatic melanoma Non-small cell lung cancer Thyroid cancer ``` Adverse Effects: Dermatologic toxicity (e.g., rash) GI toxicity (e.g., nausea, diarrhea) Fatigue QT prolongation Cardiomyopathy Febrile reactions Hyperglycemia Venous thromboembolism ```

Question 61

Treatment of Acute Chemotherapy-Induced Nausea and Vomiting (< 24 hours after chemotherapy; usually occurring 1–2 hours after chemotherapy)

Answer 61

- 5-HT3 antagonists (ondansetron, granisetron) (are most effective when used prophylactically to prevent vomiting) - Dopamine receptor antagonists (prochlorperazine, metoclopramide)

Question 62

Treatment of Delayed Chemotherapy-Induced Nausea and Vomiting (> 24 hours after chemotherapy)

Answer 62

NK1 antagonists (aprepitant, fosaprepitant)

Question 63

Lenalidomide

Answer 63

Derivative of thalidomide Mechanism: - Antiemetic get used in pregnancy until significant teratogenic effects were identified - Increases the binding of the E3 ubiquitin ligase complex to specific transcription factors that are over expressed in myeloma cells. Binding attaches ubiquitin to the transcription factors, which leads to their subsequent destruction by proteasome. Because these transcription factors are required for myeloma cell survival, diminished intracellular concentrations cause cell death. Clinical Use: Mantle cell lymphoma Myelodysplastic syndrome (some cases are caused by B cell proliferation)

Question 64

Amifostine

Answer 64

Mechanism: Free radical scavenger Clinical Use: Nephrotoxicity from platinum compounds

Question 65

Dexrazoxane

Answer 65

Mechanism: Iron chelator Clinical Use: Cardiotoxicity from anthracyclines

Question 66

Leucovorin (Folinic Acid)

Answer 66

Mechanism: Tetrahydrofolate precursor Clinical Use: Myelosuppression from methotrexate (leucovorin “rescue”); also enhances the effects of 5-FU

Question 67

Mesna

Answer 67

Mechanism: Sulfhydryl compound that binds acrolein (toxic metabolite of cyclophosphamide/ifosfamide) Clinical Use: Hemorrhagic cystitis from cyclophosphamide/ ifosfamide

Question 68

Rasburicase

Answer 68

Mechanism: Recombinant uricase that catalyzes metabolism of uric acid to allantoin Clinical Use: Tumor lysis syndrome

Question 69

Ondansetron

Answer 69

Mechanism: 5-HT3 receptor antagonists Clinical Use: Acute nausea and vomiting (usually within 1-2 hr after chemotherapy)

Question 70

Prochlorperazine

Answer 70

Mechanism: D2 receptor antagonists Clinical Use: Acute nausea and vomiting (usually within 1-2 hr after chemotherapy)

Question 71

Aprepitant

Answer 71

Mechanism: NK1 receptor antagonists Clinical Use: Delayed nausea and vomiting (>24 hr after chemotherapy)

Question 72

Filgrastim

Answer 72

``` Mechanism: Recombinant G(M)-CSF ``` Clinical Use: Neutropenia

Question 73

Epoetin alfa

Answer 73

Mechanism: Recombinant erythropoietin Clinical Use: Anemia

Question 74

Granisetron

Answer 74

Mechanism: 5-HT3 receptor antagonists Clinical Use: Acute nausea and vomiting (usually within 1-2 hr after chemotherapy)

Question 75

Metoclopramide

Answer 75

Mechanism: D2 receptor antagonists Clinical Use: Acute nausea and vomiting (usually within 1-2 hr after chemotherapy)

Question 76

Fosaprepitant

Answer 76

Mechanism: NK1 receptor antagonists Clinical Use: Delayed nausea and vomiting (>24 hr after chemotherapy)

Question 77

Sargramostim

Answer 77

``` Mechanism: Recombinant G(M)-CSF ``` Clinical Use: Neutropenia