B.30

Question 1

Drugs used in cancer treatment II (cytotoxic agents targeting DNA)

Answer 1

Alkylating agents:
Bis(chloroethyl)amines: Cyclophosphamide
Nitrosoureas: Carmustine
Intercalating antibiotics: Dactinomycin, Bleomycin
Platinum analogs: Cisplatin, Oxaliplatin
Imidazotetrazines: Temozolomide
Non-classic drugs: Dacarbazine

Question 2

Cyclophosphamide

Answer 2

Chemistry: derived from mustard gas, the group called Bis(chlorethyl)amine;
MOA: Alkylating agent.
(1)prodrug,
(2)alkylates DNA on N7 of Guanosine, where it forms cross-links inside of DNA chain or between the 2 chains→this leads to rupture in the dsDNA,
(3)inhibits both T and B cells;
IND: (immunosuppressive drug), SLE, Systemic sclerosis, vasculitis diseases, autoimmune glomerulonephritis, BM transplantation;
Dose: 2-10(12) mg/kg/T p.o OR as bolus treatment (750-1000mg monthly i.v.);
SEs: BM suppression, Oligospermia/ovarian dysfunction, GI disturbances, Hemorrhagic cystitis, Teratogenic (FDA category D), possibly mutagenic

Question 3

Dacarbazine

Answer 3

MOA: Alkylating agent. Mechanism not fully understood, besides alkylating (leading to dsDNA rupture) it might inhibit the transfer of methionine to the tRNA, not specific for cell cycle;
IND: Hodgkin’s lymphoma, soft tissue sarcomas (except mesothelioma and Kaposi sarcoma), neuroblastoma, melanoma;
SEs: myelosuppression, infections, hepatotoxicity, visual disturbances, can cause blisters

Question 4

Temozolomide

Answer 4

MOA: Alkylating agent. Alkylates a nucleotide on the DNA where it forms cross links → rupture in dsDNA; IND: Brain tumors (glioblastoma, anaplastic astrocytoma);
SEs: myelosuppression, neurotoxicity, infections (Pneumocystic pneumonia)

Question 5

Cisplatin, Oxaliplatin

Answer 5

MOA: Alkylating agent.
Alkylates a nucleotide on the DNA where it forms cross links → rupture in dsDNA;
IND: (N)SCLC, lung, breast, ovarian, esophageal, cholangiocarcinoma, colorectal (only Oxaliplatin) cc., head and neck tumors;
SEs: Nephro- and ototoxicity (Cisplatin→requires high level of hydration), neurotoxicity (→paresthesia, pain), myelosuppression, vomiting

Question 6

Dactinomycin, Bleomycin

Answer 6

Chemistry: DNA and iron binding domain containing protein;
MOA: Intercalating antibiotics. after binding to the DNA, causing breakages in the DNA with the formation of free radicals → abberation of the chromosomes. Specific for the G2 phase;
IND: Hodgkin’s- and non-Hodgkin’s lymphomas, germ cell tumors, head and neck tumors, squamous cell tumors of the skin/vulva/cervix;
SEs: Lung toxicity (pneumonitis, dyspnea, fibrosis, crepitation during inhalation), dermatological, mucositis, alopecia, anorexia