Cancer Chemo Drugs

Question 1

Alkylating agents: cell cycle, MoA

Answer 1

cyclophosphamide, ifosphamide.
cell cycle non-specific
covalently bind alkyl group to DNA (N7 position of guanine) to inhibit DNA replication
and cause single and double stranded breaks and cross-linking.
Main side effect of cyclophosphamide and ifosfamide is hemorrhagic cystitis

Question 2

What class is cyclophosphamide? What are the major side effects? Treatment of sides?

Answer 2

alkylating agent
side effect is hemorrhagic cystitis; cardiac toxicities at high doses
prevent hemorrhagic cystitis with MESNA rescue that binds the harmful metabolite

Question 3

What class is ifosfamide? What are the main side effects and treatments? Treatment of sides?

Answer 3

alkylating agent
causes hemorrhagic cystitis
also has neurologic and nephrotoxicities
prevent hemorrhagic crisis with MESNA

Question 4

What is cisplatin? (class) What are the major toxicities? Treatment of toxicities?

Answer 4

Platinum compound (acts similar to an alkylating agent)
Side effects include nausea (very significant)
Also significant nephrotoxicity and ototoxicity.
Try to prevent nephrotoxicity and ototoxicity with IV hydration, mannitol (promote excretion) and magnesium supplements

Question 5

What is carboplatin?

Answer 5

Platinum compound (acts like an alkylating agent)
causes more myelosuppression and allergic reactions than cisplatin
causes less nephrotoxicity and ototoxicity

Question 6

What are all the alkylating agents and alkylating-like agents I need to know (6)?

Answer 6

Pure alkylating:
1. cyclophosphamide
2. Ifofsimide
Platinum containing (alkylating-like agents):
3. cisplatin
4. carboplatin
Other:
Busulfan
Temozolomide

Question 7

What are antitumor antibiotics? (cell cycle, MOA)

Answer 7

derived from microbes
cell-cycle nonspecific
Kill via:
1. interacalation between base pairs
2. topoisomerase II inhibition (topoisomerase II is a DNA repair enzyme)
3. free radical generation leading to double and single stranded breaks.
4. Membrane disruption

Question 8

What are the anthracyclines (class, examples)

Answer 8

class: antitumor antibiotics
example: doxorubicin, other -rubicin drugs

Question 9

Doxorubicin: class, toxicity, treatment of toxicity

Answer 9

class: anthracyclines of the antitumor antibiotics

major toxicity is cardiac toxicity. try to prevent with dexrazoxane to bind free radicals

Question 10

Bleomycin: class, toxicities

Answer 10

Bleomycin is a miscellaneous antitumor antibiotic used for Hodgkin’s disease and germ cell tumors.
Bleomycin can cause pulmonary fibrosis.

Question 11

What are antimetabolites? (cell cycle, MOA)

Answer 11

S phase specific
similar to metabolites in DNA/RNA synthesis pathways.
compete for key enzymes and/or become incorporated into DNA

Question 12

What is methotrexate? class, toxicities

Answer 12

antimetabolite: folate antagonist
binds to dihydrofolate reductase and ultimately decreases DNA synthesis (prevents U –> T)
must give with rescue leucovorin that provides an alternate source of reduced folate to prevent deat of normal cells.
Side effects: mucositis, hepatotoxicity, at high doses: nephrotoxicity .

Question 13

What factors must be specially considered with methotrexate?

Answer 13

genetic polymorphisms in the methylenetetrahydofolate reducase (MTHFR enzyme) that lead to increased senstivitiy to methotrexate toxicity.

Question 14

What is cytarabine? (class) What toxicities are seen with cytarabine?

Answer 14

this is an antimetabolite and pyrimindine analogue. side effects include flu-like syndrome, cerebelar ataxia, and ocular probems (prevented with eyey drops).

Question 15

What are vinca alkaloids?

Answer 15

drugs that inhibit microtubule assembly: mitotic inhibitor

Question 16

What kind of drug is vincristine? What are side effects?

Answer 16

Vincristine is a vinca alkaloid that disrupts microtubule assembly
is is NON-myelosuppressive but does cause significant constipation and peripheral neuropathy. also causes skin irritation (less important)

Question 17

What are taxanes?

Answer 17

mitotic inhibitor that stabilizes microtubules

suffix: end in “taxel”

Question 18

What are the classes of mitotic inhibitors?

Answer 18

vinca alkaloids and taxanes

Question 19

What topoisomerase I inhibitor should I know? Cell cycle? What are its side effects?

Answer 19

Irinotecan (they all end in “ecan”)
Side effects: GI tumors, diarrhea
S phase

Question 20

What topoisomerase II inhibitors should I know? Cell cylce? Side effects?

Answer 20

Know etoposide
specific to S-G2 phase
cause allergic reactions
(it is also true that the antitumor antibiotics and the anthracyclines are are topoisomerase II inhbitors, but not given this way in lecture, grrrrrr).

Question 21

Corticosteroids are used to treat some cancers. Which ones? Side effects?

Answer 21

treat lympoblastic leukemias, lymphomas
we don’t know why they work/MoA
“good” side effects: anti-emetic, appetite stimulant
“bad” side effects surely exist, but I don’t need to memorize them.

Question 22

What kinds of hormone therapy are used in prostate cancer?

Answer 22

androgen deprivation, surgical or medical orchiectomy, anti-androgen drugs, estrogen

Question 23

How is hormone therapy useful in breast cancer?

Answer 23

some breast cancers are estrogen positive and can be treated with tamoxifen, which is anti-estrogenic in breast tissue

Question 24

asparaginase

Answer 24

MOA: depletes serum asparagine needed for protein synthesis by tumor cells. nornal cells can synthesize own asparagine.
Sides: hypersensitivity rxns (must have epipen ready).
also pancreatitis and hepatotoxicity
works better in peds pts

Question 25

bortezomib

Answer 25

used in tx of multiple myeloma and some lymphomas.
sides: peripheral neuropathy, thrombocytopenia. given subcutaneously
26S proteosome inhibitor (protein regulation and homeostasis)