Chemotherapy II: Alkylating Agents

Question 1

What do the alkylating agents alkylate?

Answer 1

N-7 of guanine

Question 2

Resistance in alkylating agents is due to:

Answer 2

Enhanced DNA repair

Binding to sulfar containing molecules

Question 3

Bis(chloroethyl)aminea (2)

Answer 3

Cyclophosphamide

Ifosfamide

Question 4

Cyclophosphamide MOA

Answer 4

Bifunctional alkylater: intrastrand cross link or interstrand cross link; DNA replication impaired

Question 5

Cyclosphosphamide activation

Answer 5

In the liver (P-450 oxidase)

Question 6

Cyclosphosphamide SE

Answer 6

Nausea, vomiting, hair loss, myelosupression

HEMATURIA (phosphoramide mustard is irritating)

Question 7

How can you decrease hematuria associated with Cyclosphosphamide?

Answer 7

Give drug in morning, frequent urination, maintain hydration

Question 8

Cyclosphosphamide Indication

Answer 8

breast cancer

NON-HODGKIN’s LYMPHOMA (diffuse large B cell)

Question 9

Ifosfamide

Answer 9

Bischloroethylamine

1/5 alkylating ability of Cyclosphosphamide

MUCH HIGHER DOSE required

Question 10

Ifosfamide SE

Answer 10

Blood in Urine
Must give Mesna (uroprotectant)

Lethargy, confusion

MYELOSUPPRESSION= d-l

Question 11

Mesna

Answer 11

Monomer binds metabolites in urine, eliminates hematuria of Ifosfamide

Question 12

Ifosfamide Indication

Answer 12

Sarcoma

Testicular cancers

Question 13

Temozolomide

Answer 13

Monofunctional alkylating agent

Question 14

Temozolomide MOA

Answer 14

Methylates DNA

Question 15

Temozolomide SE

Answer 15

Myelosuppression, nausea, vomiting, hair loss

Question 16

What must you give to a patient that is on Temozolomide for a prolonged period?

Answer 16

Prophylaxis for PCP (PJP) pneumonia

Question 17

Temozolomide Indication

Answer 17

Primary brain tumors

glioblastoma

Question 18

Platinum (Pt) Coordination Compounds MOA

Answer 18

Undergo sequential aquation reactions

aquated species = DNA reactive species

Covalently bind DNA at N7 of adenine and guanine

Question 19

Platinum (Pt) Coordination Compounds

Answer 19

Cisplatin
Carboplatin
Oxaliplatin

Question 20

Cisplatin SE

Answer 20

NEPHROTOXIC = d-l
*give with saline hydration and mannitol diuresis

emetogenic, neuropathy, hypomagnesemia, high frequency hearing loss

Question 21

What should you check in a patient taking Cisplatin?

Answer 21

Mg levels

Question 22

What should you co-administer with Cisplatin?

Answer 22

Saline hydration and mannitol diuresis

Question 23

Cisplatin Indication

Answer 23

Curative in TESTICULAR CANCER

lung, ovary, head, neck, bladder cancer

Question 24

What type of patient should not receive cisplatin?

Answer 24

CHF, renal insufficiency

Must be able to tolerate fluid load

Question 25

Why is Cisplatin difficult to administer

Answer 25

Patient has to be in clinic for a very long time

Question 26

Is Carboplatin nephrotoxic?

Answer 26

NO!

Question 27

Carboplatin dose-limiting SE

Answer 27

MYELOSYPPRESSION

Question 28

If a patient is resistant to cisplatin, can you give carboplatin instead?

Answer 28

NO! Cross resistant

Question 29

Can you give carboplatin to a patient on dialysis?

Answer 29

YES! Easier to give!

Question 30

Carboplatin indications

Answer 30

Same activity as cisplatin

Question 31

Oxiplatin indication

Answer 31

COLORECTAL CANCER

Question 32

Oxiplatin dose-limiting SE

Answer 32

MYELOSUPPRESSION

Question 33

Oxiplatin SE (others)

Answer 33

Vein irritant (portacath) Acute cold induced neuropathy Chronic sensory neuropathy

Question 34

Plant Alkaloids

Answer 34

Vincristine, Vinblastine, Taxol, Etoposide

Question 35

Which of the plant alkaloids are cell cycle specific?

Answer 35

Vincristine, Vinblastine, Taxol

Question 36

Which of the plant alkaloids inhibit mitotic spindle formation

Answer 36

Vincristine, Vinblastine

Question 37

Which of the plant alkaloids inhibits the breakdown of the mitotic spindle?

Answer 37

Taxol

Question 38

Which of the plant alkaloids inhibits topoisomerase II?

Answer 38

Etoposide

Question 39

Vincristine MOA

Answer 39

Prevents polymerization of tubulin | Cell cyle specific (M-phase)

Question 40

In which patients should you lower the dose of Vincristine?

Answer 40

Pts with elevated bilirubin (excreted in the bile)

Question 41

Vincristine dose-limiting SE

Answer 41

NEUROPATHY | loss of ankle jerk reflexes, N/T in fingers

Question 42

Does vincristine cause myelosuppresion?

Answer 42

NO!

Question 43

Vincristine indications

Answer 43

Lymphoma, Hodgkin's disease, Lymphoblastic leukemia

Question 44

What are the differences between vincristine and vinblastine?

Answer 44

Vinblastin is less neurotoxic but causes more myelosuppression

Question 45

Paclitaxel = Taxol MOA

Answer 45

Cell cycle specific (M-phase) | Prevents tubulin disassembly

Question 46

In which patients should you dose reduce Taxol

Answer 46

Hepatic dysfunction

Question 47

Taxol SE

Answer 47

Myelosuppression, hair loss, nausea, vomiting, stomatitis, peripheral sensory neuropathy, myalgias, arthralgias *Premedicate to prevent allergic reactions

Question 48

Carbotaxol = Carboplatin + taxol

Answer 48

Use to treat lung cancer, ovarian cancer, GE junction cancer

Question 49

Taxol Indication

Answer 49

OVARIAN, LUNG, GASTROESOPHAGEAL, BREAST cancers

Question 50

Docetaxel indication

Answer 50

prostate cancer

Question 51

Albumin bound paclitaxel benifits

Answer 51

No allergic reactions Less myelosuppression Less neuropathy

Question 52

Carbaxitaxel indication

Answer 52

Prostate cancer

Question 53

Etoposide MOA

Answer 53

Cell cycle specific (G1-S phase) Inhibits topoisomerase II Double strand DNA breaks

Question 54

Etoposide SE

Answer 54

Nausea, vomiting, hair loss | MYELOSUPPRESSION = d-l

Question 55

What is the total dose you can give of Etoposide

Answer 55

2 gm/M^2 | LEUKEMOGENIC

Question 56

Who should you dose reduce etoposide in?

Answer 56

Renal/hepatic dysfunction

Question 57

Etoposide Indication

Answer 57

TESTICULAR, lung cancer (small cell), lymphomas