Alkylating Agents And Cell Cycle Non-specific Drugs (Fitz)

Question 1

Name the triazene drugs and their therapeutic uses:

Answer 1

Dacarbazine-metastatic melanoma
Procarbazine-malignant glioma
Temozolomide-tx resistant glioma and astrocytoma

Question 2

Name the nitrosureas and therapeutic uses

Answer 2

Carmustine-brain tumors, lymphoma, melanoma
Lomustine-brain tumors, lymphoma, melanoma
STREPTOZOCIN-INSULINOMAS (BUT CAUSES DIABETES), selective at islet B cells

Question 3

MOA of cylophosphamide & Ifosfamide, administration, and where is it activated?

Answer 3

Crosslinks DNA

PO

Liver CYP450 activation

These are Nitrogen mustards

Question 4

Transporters targeted by Melphalan? Therapeutic use?

Answer 4

Phenylalanine receptors

Multiple myeloma

Nitrogen mustard drug

Question 5

Administration route of Chlorambucil and therapeutic use?

Answer 5

Oral

CLL

Question 6

Therapeutic use for Busulfan and class of drug?

Answer 6

CML

Alkyl sulfonate-Nitrogen mustard

Question 7

Therapeutic use of Estramustine?

Answer 7

Advanced prostate cancer

Anti-androgen and alkylation

Question 8

How do bifunctional agents cause damage? What about monofunctional agents?

Answer 8

Bifunctional agents-Crosslinking

Monofunctional agents-Alkylation

Question 9

Mechlorethamine, Cyclophosphamide, Ifosfamide, Estramustine are what type of cancer drugs?

Answer 9

Nitrogen mustards

Question 10

This drug has instantaneous activation by water upon infusion –> potent vesicant can cause blisters, necrosis if extravasation occurs

Answer 10

Mechlorethamine

Part of MOPP: Hodgkins disease

Question 11

What CYP450 enzymes activate cyclophosphamide and Ifosfamide?

Answer 11

CYP2B6 and CYP3A4

Question 12

This breakdown product of cyclophosphamide is a urotoxic metabolite in the bladder:

This breakdown product of cyclophosphamide is the active metabolite in tumor:

Answer 12

Acrolein

Phosphoramide mustard

Question 13

Ifosfamide is similar to cyclophosphamide in its breakdown products and toxicities with the addition of this toxicity:

Answer 13

Chloracetaldehyde Neurotoxicity

Question 14

___ is for hemorrhagic cystitis caused by Acrolein, a toxic cyclophosphamide metabolite. If given prophylactically, it will react with acrolein and diminish its toxic effect in the bladder

Answer 14

MESNA

Creates non-toxic thiol conjugate

Side effects: Hypersensitivity rxn, pre-tx with anti-histamines, corticosteroids, or both

Question 15

Benefit of estramustine? Risk?

Answer 15

Benefit: anti-androgenic effects for prostate tumors

Risk: venous thromboembolism

Question 16

Carmustine, Lomustine, and Streptozocin are what type of cancer drugs? Dual actions?

Answer 16

Nitrosureas

DNA alkylation and protein carbamoylation

Question 17

Administration of carmustine? Lomustine?

Dose limiting toxicity of nitrosureas that penetrate CNS?

Answer 17

Carmustine-IV

Lomustine-PO

Dose limiting toxicity: myelosuppression

Question 18

Dacarbazine, temozolomide, and procarbazine are what type of cancer drugs?

Answer 18

Triazenes

Question 19

Route of admin of Dacarbazine? CYP450 activation? Activated metabolite? Does it penetrate CNS effectively?

Answer 19

IV

CYP450 1A activation

MTIC activated metabolite

Nope

Question 20

Route of admin of Temozolomide? Activated metabolite? Therapeutic uses?

Answer 20

PO

MTIC

Used for refractory anaplastic astrocytoma and glioblastoma

Question 21

___ of MGMT is a biomarker for Temozolomide efficacy

Answer 21

Epigenetic silencing

Question 22

__ is a platinum-Cl complex, stable in plasma and high Cl milieu, hydrolyses in cell to active agent, has complex elimination d/t cell uptake

Answer 22

Cisplatin

Question 23

__ is a more stable analog of cisplatin and renally eliminated. T1/2 of 2 hrs

Answer 23

Carboplatin

Question 24

This cisplatin-related compound has complex elimination d/t cell uptake

Answer 24

Oxaloplatin

Question 25

Therapeutic use of cisplatin? Dose-limiting toxicity?

Answer 25

Testicular cancer (with Bleomycin, Vinblastine, or Etoposide); ovarian cancer, NSCL

Renal; severe n/v; OTOTOXICITY-Acoustic n. damage, damages hair cells and get irreversible hearing loss

Question 26

Notable severe side effect of cisplatin?

Answer 26

Nephrotoxicity

About 1/3 of pts, often seen after 10 days of admin and manifested as low GFR, higher serum creatinine, and reduced serum Mg and K levels