Chemo Drugs I

Question 1

How many cell doublings are typically needed for cancer to be clinically detectable?

Answer 1

Around 30 (could take years to develop)

Question 2

List the 4 stages of metastasis

Answer 2

1. clonal evoution
2. intravasation
3. extravasation
4. growth in the distant metastatic site

Question 3

What is the Skipper Hypothesis?

Answer 3

The ability of chemotherapy to cure is inversely proportional to the tumor burder

Question 4

What are two big factors in the development of chemoresistance?

Answer 4

Faster mutation rate and Time

Treating early is better, before development of chemoresistance

Question 5

Describe

• Complete remission
• Partial remission
• Stable disease
• Progression of Disease

Answer 5

Complete remission is NOT cured. You have killed enough cells that you no long see them

Partial remission– over 50% reduction of tumor size with no new lesions

Stable disease– nothing changed with chemo (didn’t grow, didn’t shrink)

Progression of disease (worsened)

Question 6

What is the purpose of Phase I, II, and III chinical trials?

Answer 6

Phase I – determine dose and dose limiting toxicity

Phase II – determine activity

Phase III – determine efficacy

Question 7

What is the ANC? How is it used?

Answer 7

Absolute Neutrophil Count = (% segs + % bands) x Total leukocytes

Low ANC and a fever – need to be admitted with cultures drawn
Start broad spectrum ABX until PMN count begins recovering

Question 8

Ondansetron MOA

Answer 8

5HT3 antagonist used as an anti-emetic agent

Blocks 5HT3 receptors in the CTZ of the area postrema

AEs: Constipation, risk of QT prolongation

Question 9

Alkylating Agents

MOA

Answer 9

Binds covalently to DNA
-Sulfur avid

Cell cycle non-specific

Question 10

Cyclophosphamide

MOA

Answer 10

Activated in the liver by a P450 oxidase

Phosphoramide Mustard is the DNA damaging agent that binds DNA via its chlorethyl groups

Alkylation may be intrastrand or interstrand

Question 11

Cyclophosphamide

AEs

Answer 11

N/V
Hair loss
Myelosuppression

Hematuria can occur, but it is not problematic at standard doses

Question 12

Cyclophosphamide

Indications

Answer 12

Breast Cancer

Non-Hodgkin lymphoma (diffuse large B cell lymphoma)

Question 13

How is Ifosphamide different than Cyclophosphamide?

Answer 13

Ifosphamide only has 1/5 the alkylating activity of Cyclophosphamide, so it needs to be given at higher doses

Question 14

Ifosphamide

Coadministered with…?

Answer 14

Coadministered with Mensa, which is protective against Ifosphamide’s hematuria side effects

Question 15

Ifosphamide

Indications

Answer 15

Soft tissue sarcomas

Testicular cancers

Question 16

Temozolamide

MOA

Answer 16

Monofunctioning alkylating agent

Methylates the DNA

Question 17

Temozolamide

Indications

Answer 17

Glioblastoma and other primary brain tumors

Question 18

Temozolamide

AEs

Answer 18

N/V, hair loss, myelosuppression

Must give prophylaxis against PCP pneumonia

Question 19

Platinum Coordinating Compounds

General MOA

Answer 19

Alkylating agents with Platinum in +2 oxidation state

Question 20

What are the 3 main Platinum Coordinating Compounds?

Answer 20

Cisplatin
Carboplatin
Oxaliplatin

Question 21

General Mechanism of resistance to DNA alkylating agents

Answer 21

Nucleotide excision repair molecules can break the alkylating agents

Question 22

Cisplatin

Indications

Answer 22

Testicular cancer (curative)

Lung, ovary, head and neck, bladder cancers too

Question 23

Cisplatin

Dose limiting toxicity

Answer 23

Nephrotoxicity (high doses will ruin the kidneys)

Cisplatin is also excreted by the kidneys, so it is often given with saline and maybe a mannitol diuretic. Therefore burdensome to administer in clinic

Question 24

Cisplatin

Contraindications

Answer 24

Renal impairment

Impaired cardiac or respiratory function (may not handle the high fluid load taken with cisplatin)

Question 25

Carboplatin

Indications

Answer 25

Testicular cancer (curative)

Lung, ovary, head and neck, bladder cancers too

MAY be given to someone on dialysis

Question 26

Carboplatin

Dose limiting toxicity

Answer 26

Myelosuppression

Question 27

Why would carboplatin be preferred over cisplatin?

Answer 27

Carboplatin is also excreted by the kidneys, but it is NOT nephrotoxic.

You can give carboplatin to someone on dialysis or someone who couldn’t handle the fluid overload with cisplatin

Question 28

Oxaliplatin

Indications

Answer 28

Colorectal cancer (doubles survival)

Question 29

Oxaliplatin

AEs

Answer 29

Myelosuppression
N/V
Vein irritant

Acute cold induced neuropathy

Chronic sensory neuropathy

Jaw pain with FIRST CHEW after oxaliplatin (it goes away)

Question 30

Vincristine

MOA

Answer 30

Prevents polymerization of tubulin in M phase (cell cycle specific)

Question 31

Vincristine

AEs

Answer 31

Neuropathy is dose limiting (esp if they lose fine motor activity)

Question 32

Vincristine

Indications

Answer 32

Lymphoma

Hodgkin disease

Lymphoblastic Leukemia

Question 33

Paclitaxel (Taxol)

MOA

Answer 33

Prevents tubulin disassembly (M phase specific)

Question 34

Paclitaxel (Taxol)

AEs

Answer 34

Hepatic metabolism

Myelosuppression, hair loss, N/V, stomatitis, peripheral sensory neuropathy

Question 35

Paclitaxel (Taxol)

Indications

Answer 35

Ovarian, Lung, GI, Breast cancers

Question 36

Etoposide

MOA

Answer 36

Produces DNA double stranded breaks by targeting topoisomerase II

Blocks G1 –> S

Question 37

Etoposide

AEs

Answer 37

N/V, hair loss, Myelosuppression

Reduce dose in renal or hepatic dysfunction

Question 38

Etoposide

Indications

Answer 38

Testicular Cancer
Lung cancer
Lymphomas