Chemotherapy

Question 1

Alkylating agents MOA:

Answer 1

Introduce alkyl groups in DNA, and cause DNA crosslinks and strand breaks.

Question 2

Alkylating agents CCS:

Answer 2

Cell-cycle-nonspecific, but cytotoxicity is enhanced in growing/dividing cells.

Question 3

Mechlorethamine class and CCS:

Answer 3

Alkylating agent (nitrogen mustard); cell-cycle-nonspecific.

Question 4

Mechlorethamine indications:

Answer 4

Hodgkin’s and non-Hodgkin’s lymphoma.

Question 5

Cyclophosphamide class and CCS:

Answer 5

Alkylating agent (nitrogen mustard); cell-cycle phase-nonspecific.

Question 6

Cyclophosphamide metabolism:

Answer 6

Activated by liver CYP450 system. Activation forms acrolein (bladder toxicity).

Question 7

Cyclophosphamide indications:

Answer 7

Very broad spectrum of activity

Question 8

Cyclophosphamide toxicity:

Answer 8

May cause sterile hemorrhagic cystitis. Can be partially prevented with the drug Mesna.

Question 9

Carmustine class:

Answer 9

Alkylating agent (nitrosoureas)

Question 10

Carmustine indication (important):

Answer 10

Treatment of brain tumors (rapidly crosses BBB)

Question 11

Methotrexate class and MOA:

Answer 11

Folate analog; Binds to dihydrofolate reductase (DHFR) and prevents formation of tetrahydrofolate (THF).

Question 12

Often co-administered with methotrexate:

Answer 12

Leucovorin (folinic acid; a fully reduced folate coenzyme that does not require reduction by DHFR.)

Question 13

Methotrexate contraindication:

Answer 13

Binds to serum albumin so avoid other drugs that will displace it from albumin.

Question 14

Methotrexate important toxicity:

Answer 14

Renal tubular necrosis.

Question 15

Methotrexate indication:

Answer 15

Acute lymphocytic leukemia; choriocarcinoma (MTX is #1).

Question 16

5-FU class and MOA:

Answer 16

Pyrimidine analog. Activated in cells to FUTP which inhibits RNA synthesis, to FdUMP which interferes with thymidylate synthetase and ultimately DNA synthesis.

Question 17

5-FU CCS:

Answer 17

S phase

Question 18

5-FU indications:

Answer 18

carcinoma of the stomach, COLON, pancreas, ovary, head and neck, BREAST, bladder. Also as a topical cream for basal cell carcinoma. Mostly GI cancers.

Question 19

Cytarabine class and MOA:

Answer 19

Pyrimidine analog. Competes with cytidine for all 3 phosphorylation steps to dCTP. Cytarabine tri-phosphate then competes with dCTP for incorporation into DNA and causes DNA chain termination.

Question 20

Cytarabine CCS:

Answer 20

S phase. Continuous infusion increases probability of killing tumor cells not initially in S phase.

Question 21

Cytarabine toxicity:

Answer 21

Neurotoxicity.

Question 22

Cytarabine indications:

Answer 22

Acute leukemias.

Question 23

What is a nadir:

Answer 23

the lowest or deepest point in a WBC count-graph.

Question 24

Mercaptopurine class and MOA:

Answer 24

Purine analog; is converted in cells to a ribonucleotide that inhibits RNA and DNA synthesis.

Question 25

Mercaptopurine CSS:

Answer 25

S phase.

Question 26

Mercaptopurine indications and important:

Answer 26

Acute leukemias. *Need to check for mutations in TPMT which metabolizes 6-MP to inactive form. If there is 1 copy of nonfunctional TPMT, reduce dose to prevent serious bone marrow toxicity.

Question 27

Hydroxyurea MOA:

Answer 27

Inhibits ribonucleotide reductase by blocking conversion of ribonucleotides to dNTPs, thereby preventing DNA synthesis. Causes cells to arrest at G1-S interface.

Question 28

Hydroxyurea CSS:

Answer 28

S phase.

Question 29

Hydroxyurea useful with....

Answer 29

radiation.

Question 30

Hydroxyurea indications:

Answer 30

granulocytic leukemia, head and neck cancer.

Question 31

Hydroxyurea toxicity:

Answer 31

Hematopoietic depression.

Question 32

Vinblastine class:

Answer 32

Vinca alkaloid.

Question 33

Vinca alkaloids CSS and MOA:

Answer 33

M phase specific. Binds to tubulin, inhibiting proper formation of MTs and mitotic spindle.

Question 34

Vinblastine indications:

Answer 34

Breast cancer (also H and nonH lymphoma)

Question 35

Vinblastine toxicity:

Answer 35

Strongly myelosuppressive, EPITHELIAL ULCERATIONS.

Question 36

Vincristine class:

Answer 36

Vinca alkaloid.

Question 37

Vincristine indications:

Answer 37

Treatment of acute lymphocytic leukemia, Wilm's tumor, neuroblastoma, rhabdomyosarcoma (also H and nonH).

Question 38

Vincristine toxicity:

Answer 38

Alopecia, significantly less myelosuppression than vinblastine, Neuromuscular abnormalities (ex: peripheral neuropathy).

Question 39

Paclitaxel class and CSS:

Answer 39

Taxane; blocks late in G2 phase (a phase more sensitive to radiation).

Question 40

Paclitaxel MOA:

Answer 40

Enhances assembly and stability of MTs by binding to B-subunit of tubulin. Polymerization is stabilized so MTs cannot dissociate. Taxol can interfere with DNA repair, intensifying the effects of DNA damage by cisplatin or cyclophosphamide.

Question 41

Paclitaxel indications:

Answer 41

Refractory ovarian cancer; breast. Can interfere with DNA repair so could be used with cisplatin or cyclophosphamide.

Question 42

Paclitaxel toxicity:

Answer 42

Dose-limiting leukopenia, peripheral neuropathy, myalgia/arthralgia.

Question 43

Doxorubicin class and MOA:

Answer 43

Antitumor antibiotics, cycle-specific phase-nonspecific. 1. Intercalates between DNA base pairs, distorting DNA helix. 2. Causes lipid peroxidation and free radical generation. 3***. Binds to DNA and topoisomerase II. **Doxorubicin is one of the few drugs with some anti-angiogenic properties***.

Question 44

Doxorubicin indication:

Answer 44

H and nonH, breast, ovary, small-cell lung.

Question 45

Doxorubicin toxicity:

Answer 45

Cardiomyopathy***

Question 46

Bleomycin class and CSS:

Answer 46

Antitumor antibiotic; phase-specific for G2.

Question 47

Bleomycin MOA:

Answer 47

Iron is critical to its mechanism. Glycopeptides bind DNA, causes oxidative-like damage to DNA which leads to DNA strand breaks.

Question 48

Bleomycin indications:

Answer 48

Germ cell tumors of testes and ovaries.

Question 49

Bleomycin toxicity:

Answer 49

Dose-related PULMONARY TOXICITY. Vesiculation of the skin, skin hyperpigmentation. *Lungs and skin have lowest levels of bleomycin hydrolase (which inactivates bleomycin).

Question 50

Etoposide MOA:

Answer 50

Stabilizes DNA-topoisomerase II complexes, resulting in dsDNA breaks.

Question 51

Etoposide CSS:

Answer 51

Maximal effects in late G2 phase (also late S).

Question 52

Etoposide indications:

Answer 52

Lymphomas, acute nonlymphocytic leukemia, small cell carcinoma of the lung, testicular tumors.

Question 53

Etoposide toxicity:

Answer 53

Leukopenia

Question 54

Filgrastim MOA, use, side effect:

Answer 54

Stimulates granulocyte production by marrow. Given after myelosuppressive agents to speed neutrophil recovery. Bone pain.

Question 55

Trastuzumab MOA and use:

Answer 55

Monoclonal antibody that binds to HER2 receptor. Use with metastatic breast cancers that overexpress HER2 (which tend to be less responsive to anti-estrogen strategies) First line treatment with paclitaxel for breast cancer.

Question 56

Trastuzumab toxicity:

Answer 56

Cardiomyopathy, hypersensitivity, infusion reaction.

Question 57

Cisplatin MOA:

Answer 57

Platinum coordination complex. Activated species causes DNA crosslinks.

Question 58

Cisplatin CSS:

Answer 58

Cycle-specific, phase nonspecific.

Question 59

Cisplatin toxicity:

Answer 59

*Nephrotoxicity*, ototoxicity, electrolyte disturbances.

Question 60

Procarbazine MOA, CSS:

Answer 60

Activated in vivo to a methylating agent which causes chromosomal damage. Most effective in G1 and S phase. Atypical alkylating agent; no cross resistance with other alkylating agents.

Question 61

Procarbazine indication:

Answer 61

H lymphoma.

Question 62

Prednisone MOA:

Answer 62

Binds to steroid receptors, depresses RNA synthesis of many growth-related genes. May arrest cells in G1. Induces nucleases which may modulate cell lysis.

Question 63

Prednisone uses:

Answer 63

Anti-emetic effect. Palliative therapy. Used for acute and chronic lymphocytic leukemia, H and nonH, breast cancer.

Question 64

Tamoxifen MOA:

Answer 64

Antiestrogen that blocks estrogen receptors. Activated by CYP2D6. Generally cytostatic; tumor will grow back once therapy is stopped.

Question 65

Tamoxifen uses:

Answer 65

Breast cancer, breast cancer prophylaxis in women at high risk. May prevent post-menopausal osteoporosis.

Question 66

Tamoxifen toxicity:

Answer 66

Hot flashes, fatigue, nausea, bone and other musculoskeletal pain. *May increase rate of uterine/endometrial cancer.

Question 67

Letrozole MOA:

Answer 67

Aromatase inhibitor; inhibits conversion of androgens to estrogens in all tissues by binding to aromatase CYP19.

Question 68

Letrozole use:

Answer 68

1st line treatment of hormone receptor-positive or receptor-unknown breast carcinoma in post-menopausal women. *Adjuvant therapy for postmenopausal women with advanced breast cancer who have received 5 years of adjuvant tamoxifen therapy.

Question 69

Letrozole toxicity:

Answer 69

Hot flashes, fatigue, nausea, bone and other musculoskeletal pain (no difference to tamoxifen).

Question 70

Leuprolide MOA:

Answer 70

Analog of gonadotropin-releasing hormone (GnRH). After 2-4 weeks it desensitizes GnRH signaling, inhibiting LH/FSH secretion thereby decreasing testosterone synthesis to castration levels.

Question 71

Leuprolide use and toxicity:

Answer 71

Advanced hormonally responsive prostate cancer. Hot flashes, impotence.

Question 72

Flutamide MOA and use:

Answer 72

Non steroidal antiandrogen that blocks androgen receptors. Metastatic prostate cancer.

Question 73

Flutamide toxicity:

Answer 73

Gynecomastia

Question 74

Imatinib (Gleevec) MOA and use:

Answer 74

CKIT tyrosine kinase inhibitor, blocks cell proliferation and increases apoptosis. Approved for CML and GI stromal tumors.

Question 75

Sequential blockade:

Answer 75

Simultaneous action of two inhibitors acting on different enzymes of a linear metabolic pathway.

Question 76

Concurrent inhibition:

Answer 76

Inhibitors block two separate pathways that lead to the same end product.

Question 77

Complementary inhibition:

Answer 77

One of the inhibitors affects the function of an end product, the other inhibitor affects the synthesis of the end product.

Question 78

Rescue:

Answer 78

"Rescue" the patient's normal cells from the treatment.

Question 79

Synchronization:

Answer 79

Tumor cells synchronized so they are in one phase and then use agent that is specific for that phase.

Question 80

Recruitment:

Answer 80

The mobilization of slowly proliferating or non-proliferating cells to more rapid proliferation.

Question 81

Antimetabolites CSS:

Answer 81

S phase specific.

Question 82

What are biological response markers?

Answer 82

Naturally occurring proteins or therapeutic molecules designed to mimic or impact natural proteins. Intent is to alter patient's own biological response to tumor, less probability of serious toxicity.

Question 83

Procarbazine SEs:

Answer 83

Secondary malignancy if used too long.

Question 84

Prednisone SEs:

Answer 84

Immunosuppression.