Chemo- Drugs that cause DNA strand breaks Flashcards
(25 cards)
What antibiotics are used to treat cancer? MOA?
Bleomycin and Dactinomycin
Free radical generation–> DNA strand breaks
What is the clinical use of Bleomycin?
Testicular cancer (wi/vinblastine, cisplatin, or etoposide)
What are Doxorubicin and Epirubicin used to treat?
Very wide spectrum drugs- Mostly breast and ovarian cancer, but also lung, thyroid, lymphoma, sarcoma, etc.
What is Daunorubicin used to treat?
Leukemia (ALL, AML)
What is Idarubicin used for?
Leukemia (AML, ALL, and CML in blast crisis)
What is Mitoxantrone used to treat?
Predominately breast cancer. Also prostate and NHL
What is the Dose Limiting Toxicity of Bleomycin?
Pulmonary Fibrosis (cumulative dose-related toxicity)
What is the Dose Limiting Toxicity of the Anthracyclines?
Cardiotoxicity, dilated cardiomyopathy, and CHF
What part of the cell cycle do Bleomycin and the Anthracyclines act on?
G2 phase, and S phase (anthracyclines)
What are Cyclophosphamide and Ifosfamide converted to in the body and by what?
Converted into phosphoramide mustard + acrolein by CYP450 in the liver
What side effect is unique to Ifosfamide and what causes it?
Severe neurotoxicity from Chloroacetaldehyde (seizures, coma, neuropathy) other drugs may have minimal neurotoxicity
Which triazine penetrates the CNS well and is useful for brain cancer?
Temozolomide
What is Cisplatin used for?
Testicular cancer (wi/bleomycin, vinblastine, or etoposide), ovarian cancer, NSCL cancer
What are the Dose Limiting Factors of Cisplatin?
Renal damage, severe nausea/vomiting, ototoxicity, acoustic nerve damage
What is Oxaloplatin used for?
Colorectal cancer (FOLFOX regimen)
What is Carboplatin used for?
Ovarian cancer
What is the Dose Limiting Toxicity of Oxaloplatin?
Cold-Induced Neuropathy and Neutropenia
What is Mechlorethamine used for?
Hodgkin’s Disease (MOPP regimen)
What type of chemo drugs are dose-dependent?
Cell Cycle non-specific drugs
What is Temozolomide used to treat?
Treatment resistant glioma and astrocytoma- Good CNS distribution
What are the Nitrosoureas used for chemo and what do they treat?
Carmustine and Lomustine
Used for brain tumors, lymphoma, and melanoma
What are the Aziridines and what is their MOA?
Thiotepa, Mitomycin C, and Altretamine
Cause G-G crosslinking (bifunctional agents)
What enzyme confers resistance or susceptibility to Temozolomide treatment?
O6-MGMT enzyme
If gene is silenced–> better outcome with drug (normally repairs DNA damage)
How does activation of Dacarbazine and Temozolomide differ?
Dacarbazine- CYP450 activation to MTIC
Temozolomide- Spontaneous activation in gut to MTIC
(MTIC adds methyl group to DNA)
