B.33. Cancer Chemotherapy ll (Alkylating agents)

Question 1

list the alkylating agents

Answer 1

cyclophosphamide
cisplatin
oxaliplatin
dacarbazine
temozolomide 
bleomycin
dactinomycin

Question 2

which alkylating agent is cell cycle specific (ccs)?

Answer 2

bleomycin

*all the others are CCNS

Question 3

how do alkylating agents exert their cytotoxic effects?

Answer 3

they covalently bind to nucleophilic groups on cell constituents (e.g: DNA alkylation)
most toxic to rapidly dividing cells, but do not discriminate between cycling and resting cells.

Question 4

what alkylating agents cause lung fibrosis?

Answer 4

cyclophosphamide

bleomycin

Question 5

what prevents nephrotoxicity in Cisplatin?

Answer 5

Amifostine and saline infusions

Question 6

what kind of regimen is Oxaliplatin part of?

Answer 6

FOLFOX regimen (colon cancer)

Question 7

a side effect of oxaliplatin

Answer 7

neurotoxicity

Question 8

which alkylating agent causes SIADH and Hemorrhagic cystitis?

Answer 8

cyclophosphamide

Question 9

what is given as an antidote to reduce the incidence of hemorrhagic cystitis when giving cyclophosphamide?

Answer 9

Mesna

Question 10

what is the name of the metabolic product from cyclophosphamide that causes hemorrhagic cystitis?

Answer 10

acrolein

Question 11

contraindications of alkylating gents

Answer 11

gravidity, nursing, and general disability

Question 12

which alkylating agents require hepatic P450 activation

Answer 12

cyclophosphamide

dacarbazine

Question 13

which alkylating agents are platinum-based?

Answer 13

Cisplatin

Oxaliplatin

Question 14

what does cyclophosphamide do?

Answer 14

it attacks guanine N7–> dysfunctional DNA

Question 15

how is cyclophosphamide given?

Answer 15

partnteral/ oral

Question 16

how is cyclophosphamide classified chemically?

Answer 16

as nitrogen mustard

Question 17

how does cisplatin/oxaliplatin work?

Answer 17

cross-links DNA strands

Question 18

indications for dacarbazine

Answer 18

H&M
Hodgkin lymphoma
Melanoma

Question 19

which drugs are usually used in combination with Dacarbazine?

Answer 19

Vinblastine
Bleomycin
doxorubicin

Question 20

side effects of dacarbazine

Answer 20

nausea, vomiting
alopecia
skin rash
photosensitivity
myelosuppression

Question 21

which alkylating agents cause myelosuppression

Answer 21

cyclophosphamide
dacarbazine
dactinomycin

Question 22

which alkylating agent is activated in physiologic pH?

Answer 22

temozolomide

Question 23

what is temozolomide used for?

Answer 23

CNS tumors (e.g: glioblastoma)

Question 24

side effects of temozolomide

Answer 24

nausea, vomiting

myelosuppression

Question 25

indications for cyclophosphamide

Answer 25

``` breast cancer ovarian cancer testicular cancer non- Hodgkin lymphoma CLL, ALL (children) neuroblastoma immunosuppressive therapy ```

Question 26

SE of cyclophosphamide

Answer 26

``` nausea, vomiting, myelosuppression alopecia hemorrhagic cystitis, bladder cancer SIADH lung fibrosis ```

Question 27

indications for cisplatin

Answer 27

lung cancer! testicular cancer bladder cancer ovarian cancer

Question 28

SE of cisplatin

Answer 28

nausea, vomiting (severe) nephrotoxicity neurotoxicity (ototoxicity, peripheral)

Question 29

mechanism of bleomycin

Answer 29

complexes with Fe and O₂--> free radicals formation--> DNA strand termination

Question 30

indications of bleomycin

Answer 30

Hodgkin lymphoma lymphoma testicular cancer squamous cell carcinoma

Question 31

indications of Dactinomycin (actinomycin-D)

Answer 31

Wilms tumor Ewings sarcoma Rhabdomyosarcoma gestational choriocarcinoma

Question 32

what is the mechanism of action of Dactinomycin?

Answer 32

inhibits DNA-dependent RNA polymerase--> at high doses inhibit DNA synthesis

Question 33

side effects of dactinomycin

Answer 33

nausea, vomiting Myelosuppression alopecia

Question 34

side effects of bleomycin

Answer 34

pulmonary fibrosis pneumonitis HS reaction Mucocutaneous reactions (alopecia, hyperpigmentation, blisters, hyperkeratosis)