Antineoplastic: Alkylating Agents

Question 1

Mechlorethamine

Answer 1

• mechanism: Alkylates the N7 nitrogen of a guanine residue on DNA molecule, leads to formation of cross-linkages between guanine residues in DNA chains, facilitating DNA strand breakage
• kinetics: IV
• clinical: Hodgkin’s and non-Hodgkin’s lymphoma
• toxicity/interactions: severe nausea and vomiting, bone marrow suppression
• misc: nausea and vomiting can be diminished with pre-treatment with ondanestron, granisetron, or palonosetron (drugs that end in -tron are anti-nausea)

Question 2

Cyclophosphamide

Answer 2

• mechanism: Forms DNA cross-links, resulting in inhibition of DNA synthesis and function
• kinetics: oral
• clinical: Breast cancer, ovarian cancer, non-Hodgkin’s lymphoma, CLL, soft tissue sarcoma, neuroblastoma, Wilms’ tumor, rhabdomyosarcoma
• toxicity/interactions: nausea, vomiting, bone marrow suppression, HEMORRHAGIC CYSTITIS, cardiac dysfunction, pulmonary toxicity

Question 3

Melphalan

Answer 3

• mechanism: Forms DNA cross-links, resulting in inhibition of DNA synthesis and function
• kinetics: oral (fasting) or IV
• clinical: MULTIPLE MYELOMA, breast cancer, ovarian cancer
• toxicity/interactions: nausea, vomiting, bone marrow suppression, Secondary malignancy (cumulative dose and duration dependent, includes acute myeloid leukemia, myeloproliferative syndrome, carcinoma)

Question 4

Bis-Chloroethyl Nitrosourea

Answer 4

• mechanism: Forms DNA cross-links, resulting in inhibition of DNA synthesis and function
• kinetics: IV, lipophilic and therefore distributes widely in the body, cross BBB
• clinical: BRAIN CANCER, Hodgkin’s and non-Hodgkin’s lymphoma
• toxicity/interactions: Nausea and vomiting, delayed bone marrow suppression, rarely interstitial lung disease and interstitial nephritis

Question 5

Busulfan

Answer 5

• mechanism: Forms DNA cross-links, resulting in inhibition of DNA synthesis and function
• kinetics: oral
• clinical: CML
• toxicity/interactions: nausea, vomiting, bone marrow suppression, pulmonary fibrosis, seizures, hyperpigmentation, adrenal insulficiency
• misc: Phenytoin may be used concurrently to prevent seizures

Question 6

Thiotepa

Answer 6

• mechanism: Forms DNA cross-links, resulting in inhibition of DNA synthesis and function
• kinetics: IV, intravescial instillation for treatment of bladder cancer
• clinical: Breast cancer, ovarian cancer, superficial bladder cancer
• toxicity/interactions: nausea, vomiting, bone marrow suppression

Question 7

Mitomycin

Answer 7

• mechanism: Forms DNA cross-links, resulting in inhibition of DNA synthesis and function
• kinetics: IV, topically
• clinical: esophageal carcinoma, anal cancers, breast cancers, superficial bladder cancer
• toxicity/interactions: delayed bone marrow toxicity, pulmonary fibrosis, nephrotoxicity

Question 8

Cis-Platin

Answer 8

• mechanism: Coordinates platinum, binds to N7 of guanine in DNA, forming cross-links resulting in inhibition of DNA synthesis and function
• kinetics: IV
• clinical: Non-small cell and small cell lung cancer, breast cancer, bladder cancer, cholangiocarcinoma, gastroesophageal cancer, head and neck cancer, ovarian cancer, germ cell cancer
• toxicity/interactions: NEPHROTOXICITY, severe nausea, vomiting, peripheral sensory neuropathy, ototoxicity, nerve dysfunction
• misc: does not cause BMS, use amifosten to reduce nephrotoxicity