Antineoplastics 1

Question 0

Fraction of tumor cells in replicative phase

Answer 0

Growth fraction

Question 1

Doubling time of proliferating cancer cells is constant, straight line on a semilog plot, cell kill 1st order kinetics

Answer 1

Skipper’s law

Question 2

Cells accumulate slowly at first then there is rapid growth, growth rate about 1/3 of max tumor volume, sigmoid curve

Answer 2

Gompertzian growth

Question 3

Active in al phases except g0

Answer 3

Phase nonspecific

Question 4

Active in one phase of the cycle

Answer 4

Phase specific

Question 5

Active even in g0

Answer 5

Cell cycle nonspecific

Question 6

Cell cycle specific agents

Answer 6

Antimetabolites
Bleomycin
Podophyllin alkaloids (etoposide, vp-16, teniposide, vm 26)
Plant alkaloids (vincristine, vinblastine, paclitaxel)

Question 7

Cell cycle nonspecific

Answer 7

Alkylating agents (busulfan, cyclophosphamide, mechlorethamine, melphalan, thiorepa)
Antibiotics (dactinomycin, daunorubicin, doxorubicin, plicamycin, mitomycin)
Cisplatin
Nitrosureas

Question 8

Goals of cancer treatment

Answer 8

Cure
Palliative
Adjuvant

Question 9

If 1g of tumor, 10^9 cells is the min size of early detection and 10^-5 is the tumor mutation rate per gene then such a tumor might contain 10^4 clones which might be resistant to a given drug

Answer 9

Goldie Coldman Hypothesis

Question 10

Drug resistance mechanisms

Answer 10

Decreased drug transport into cell
Reduced drug activation
Increased drug or active metabolite inactivation 
Increased DNA repair
Use of alternate pathway as source of metabolite
Increased drug transport outside of cell
Gene amplification of drug target
Alteration of target to reduce binding

Question 11

Advantages of combination chemotherapy

Answer 11

Higher response rate due to additive effects
Non overlapping host toxicities
Effective against broader range cell lines
May slow down development of or prevent resistance

Question 12

Inhibits dihydrofolate reductase, inhibits purine and dtmp biosysnthesis

Answer 12

Methotrexate

Question 13

Terminates dna chain elongation, incorporated into dna and rna

Answer 13

Cytarabine

Question 14

Intercalates with dna disrupting its function

Answer 14

Dactinomycin
Daunorubicin
Doxorubicin

Question 15

Inhibits de novo synthesis of purine ring

Answer 15

6 mercaptopurine thioguanine

Question 16

Inhibits dTMP synthesis

Answer 16

5 fluorouracil

Question 17

Scission of DNA by an oxidative process

Answer 17

Bleomycin peptide antibiotics

Question 18

Crosslinks and fragments nucleic acids

Answer 18

Alkylating agents
Nitrosureas
Cisplatin

Question 19

Alkylating agents moa

Answer 19

Alkylation of DNA at N7 of guanine

Question 20

Cell cycle specific, alkylating agents?

Answer 20

NO! Nonspecific, but replicating cells are most susceptible

Question 21

First of nitrogen mustard used clinically

Answer 21

Mechlorethamine

Question 22

Fastest acting nitrogen mustard

Answer 22

Mechlorethamine

Question 23

Hodgkin’s disease MOPP

Answer 23

Mustargen/mechlorethamine
Oncovin/vincristine
Procarbazine
Prednisone

Question 24

ABVD, newer for hodgkins

Answer 24

Adriamycin (doxorubicin/hydroxydoxorubicin) Bleomycin Vinblastine Dacarbazine (like procarbazine)

Question 25

Mechlorethamine toxicities

Answer 25

Nausea and vomiting Severe myelosuppression Inc incidence of leukemias

Question 26

Alkylating agent that is not a vesicant, needs to be converted to active form

Answer 26

Cyclophosphamide

Question 27

Very broad spectrum, component of combination therapy

Answer 27

Cyclophosphamide

Question 28

Less thrombocytopenia, more alopecia, less CNS effect compared to mechlorethamine

Answer 28

Cyclophosphamide

Question 29

Phenylalanine derivative of nitrogen mustard, not a vesicant, oral

Answer 29

Melphalan

Question 30

Bone marrow depression but Infrequent nausea and vomiting No alopecia No renal, hepatic deficits

Answer 30

Melphalan

Question 31

Slowest acting nitrogen mustard, bone marrow depression with high doses, long perio

Answer 31

Chlorambucil

Question 32

Nitrosurea, similar to bifunctional alkylating agents but with carbamoylating activity, high lipophilicity, crosses BBB

Answer 32

BCNU (carmustine)

Question 33

Alkylsulfonate

Answer 33

Busulfan

Question 34

Pulmonary infiltrates and fibrosis

Answer 34

Busulfan

Question 35

Inorganic water soluble platinum containing complex

Answer 35

Cisplatin

Question 36

Nausea and vomiting Nephrotoxicity delayed, dose limiting OTOTOXICITY Mild to mod myelosuppression

Answer 36

Cisplatin

Question 37

Alkylating agents

Answer 37

``` Mechlorethamine Cyclophosphamide Busulfan Melphalan Chlorambucil BCNU (carmustine) Cisplatin ```

Question 38

Nitrogen mustard

Answer 38

Mechlorethamine Melphalan Chlorambucil