Alkylating Agents

Question 1

Alkylating Agents (general properties)

Answer 1

Transfer alkyl groups- cross linking, strand breaks
- Replicating cells are most vulnerable- cancer, GI, BM, Hair, Skin
- Most effective in G1/S
Tox: GI- N/V, mucositis, GU
BM- neutropenia, thrombocytopenia
Extravasation
Secondary malignancy risk- AML

Question 2

Cyclophosphamide

Answer 2

• Forms DNA cross links
  Tox: Acute: GI- N/V
  Delayed- moderate depression of periph blood count, thrombocytopenia, hemorrhagic cystitis
• Severe BM depression with leukopenia w/ excess doses
• Breast cancer, widely applied

Question 3

Busulfan

Answer 3

• Forms DNA cross links
  Tox: Acute- N/V
  Delayed- Severe myelosuppression, skin pigmentation, pulm fibrosis, adrenal insufficiency

Question 4

Carmustine

Answer 4

Nitrosurea, DNA cross-linker
Orally available, highly lipid soluble
- CNS penetrance, Brain tumor tx
(carMUST have for brain tumors!)
- Acute- N/V
-Delayed- Myelosuppression
- Rare interstitial lung disease and intersitial nephritis

Question 5

Procarbazine

Answer 5

Non-classical alkylating agent

• Inhibits DNA, RNA and protein synth
• N/V
• Myelosuppression
• CNS Tox. associated with MAOIs (cytotoxic drug metabolites act as MAOIs)
• High risk of secondary malignancies
• Adverse Interaction: Hypertensive crisis- sympathomimetics, tricyclic ADs, Anti- Histamines, CNS Depressants, EtOH

Question 6

Platinum Based Alkylating Agents

Answer 6

Cisplatin, Caboplatin, Oxaliplatin

• “stick” to the DNA strands, cytotoxic at all cell stages
• Also bind to cytoplasmic and nuclear proteins
• Synergistic with other alkylating agents, Fluoropyrmidines, Taxanes

Question 7

Cisplatin

Answer 7

• Forms inter/intra DNA cross links, binds nuclear and cellular proteins
• Highly emetogenic, must give anti-emetic prophylaxis
• Nephrotoxicity
• Ototoxicity
• Irreversible nerve damage- periph. sensory defects, neuropathy

Question 8

Carboplatin

Answer 8

• Acute N/v
• Myelosuppression
• Periph sensory neuropathy
• Nephrotoxicity, Liver dysfunction

Question 9

Oxaliplatin

Answer 9

• Effective in cells with DNA MMR defects
• Acute N/V
• Acute Neurotoxicity- Laryngo-pharyngeal dysesthesia can be triggered by cold
• Delayed Diarrhea
• Delayed Neurotox- peiph sensory neuropathy, dose dependent and reversible
  Tx: CRC, part of FOLFOX Regimen