Chemo- Drugs that cause DNA strand breaks

Question 1

What antibiotics are used to treat cancer? MOA?

Answer 1

Bleomycin and Dactinomycin

Free radical generation–> DNA strand breaks

Question 2

What is the clinical use of Bleomycin?

Answer 2

Testicular cancer (wi/vinblastine, cisplatin, or etoposide)

Question 3

What are Doxorubicin and Epirubicin used to treat?

Answer 3

Very wide spectrum drugs- Mostly breast and ovarian cancer, but also lung, thyroid, lymphoma, sarcoma, etc.

Question 4

What is Daunorubicin used to treat?

Answer 4

Leukemia (ALL, AML)

Question 5

What is Idarubicin used for?

Answer 5

Leukemia (AML, ALL, and CML in blast crisis)

Question 6

What is Mitoxantrone used to treat?

Answer 6

Predominately breast cancer. Also prostate and NHL

Question 7

What is the Dose Limiting Toxicity of Bleomycin?

Answer 7

Pulmonary Fibrosis (cumulative dose-related toxicity)

Question 8

What is the Dose Limiting Toxicity of the Anthracyclines?

Answer 8

Cardiotoxicity, dilated cardiomyopathy, and CHF

Question 9

What part of the cell cycle do Bleomycin and the Anthracyclines act on?

Answer 9

G2 phase, and S phase (anthracyclines)

Question 10

What are Cyclophosphamide and Ifosfamide converted to in the body and by what?

Answer 10

Converted into phosphoramide mustard + acrolein by CYP450 in the liver

Question 11

What side effect is unique to Ifosfamide and what causes it?

Answer 11

Severe neurotoxicity from Chloroacetaldehyde (seizures, coma, neuropathy) other drugs may have minimal neurotoxicity

Question 12

Which triazine penetrates the CNS well and is useful for brain cancer?

Answer 12

Temozolomide

Question 13

What is Cisplatin used for?

Answer 13

Testicular cancer (wi/bleomycin, vinblastine, or etoposide), ovarian cancer, NSCL cancer

Question 14

What are the Dose Limiting Factors of Cisplatin?

Answer 14

Renal damage, severe nausea/vomiting, ototoxicity, acoustic nerve damage

Question 15

What is Oxaloplatin used for?

Answer 15

Colorectal cancer (FOLFOX regimen)

Question 16

What is Carboplatin used for?

Answer 16

Ovarian cancer

Question 17

What is the Dose Limiting Toxicity of Oxaloplatin?

Answer 17

Cold-Induced Neuropathy and Neutropenia

Question 18

What is Mechlorethamine used for?

Answer 18

Hodgkin’s Disease (MOPP regimen)

Question 19

What type of chemo drugs are dose-dependent?

Answer 19

Cell Cycle non-specific drugs

Question 20

What is Temozolomide used to treat?

Answer 20

Treatment resistant glioma and astrocytoma- Good CNS distribution

Question 21

What are the Nitrosoureas used for chemo and what do they treat?

Answer 21

Carmustine and Lomustine

Used for brain tumors, lymphoma, and melanoma

Question 22

What are the Aziridines and what is their MOA?

Answer 22

Thiotepa, Mitomycin C, and Altretamine

Cause G-G crosslinking (bifunctional agents)

Question 23

What enzyme confers resistance or susceptibility to Temozolomide treatment?

Answer 23

O6-MGMT enzyme

If gene is silenced–> better outcome with drug (normally repairs DNA damage)

Question 24

How does activation of Dacarbazine and Temozolomide differ?

Answer 24

Dacarbazine- CYP450 activation to MTIC
Temozolomide- Spontaneous activation in gut to MTIC
(MTIC adds methyl group to DNA)

Question 25

What class of alkylating agents is lipophilic and used primarily for brian cancers?

Answer 25

Nitrosoureas (Carmustine, Lomustine)

Good CNS distribution