Cancer Chemotherapy Flashcards
What 2 chemotherapy combinations are used to treat Hodgkin’s disease?
- MOPP
2. ABVD
What chemotherapy combination is used to treat Non-Hodgkin’s lymphoma?
CHOP
What chemotherapy combinations are used to treat breast cancer?
- CMF
2. CAF
What chemotherapy combination is used to treat small cell lung cancer?
PACE
What chemotherapy combination is used to treat germ cell?
VIP
What chemotherapy combination is used to treat cervical cancer?
BIP
What chemotherapy combination is used to treat lymphomas?
M-BACOD
What chemotherapy combination is used to treat ovarian cancer?
BEP
What chemotherapy combination is used to treat pheochromocytoma?
CVD
What chemotherapy combination is used to treat testicular cancer?
PEB
The up-regulation of p-glycoprotein pumps affects cancer drugs in what way?
Promotes the efflux of drugs out of the cell and therefore makes the cancer cell resistant to the action of the drugs.
What is cross linking DNA and what type of drugs use this mechanism?
- Blocks DNA replication and transcription by linking two bases of DNA.
- Alkylating agents
What alkylating agents are taken as prodrugs?
Cyclophosphamide and iphosphamide.
What cytotoxic agent is produced when cyclophosphamide and iphosphamide undergo oxidative phosphorylation?
Acrolein.
Mechlorethamine
- Alkylating agent
- Not excreted
- Hodgkins’ disease
Cyclophosphamide
- Alkylating agent
- Must be activated by P450 in the liver
- SIDAH (water intox)
- Tx: Burkitt’s lymphoma, acute lymphocytic leukemia
Chlorambucil
- Alkylating agent
- Hepatotoxicity
- Tx: Chronic lyphocytic leukemia
What is MESNA used for in cancer treatment therapy?
- To decrease hemorrhagic cycstitis produced by acrolein.
- Prevents acrolein from binding to bladder wall
Estramustine phosphate
- Combination of nitrogen mustard and estradiol
- PO administration
- In vivo binds to Beta-tubulin
- Antimitotic effects
- CCNS and M-phase
Busulfan
- CCNS
- S/Es: Pulmonary fibrosis and hyperpigmentation
Nitrosoureas:
- Carmustine (BCNU)
- Lomustine (CCNU)
- Semustine (Methyl-CCNU)
- Streptozotocin
- CCNS
- Lipophilic = pass blood/brain barrier
- S/Es: Pulmonary fibrosis and nephrotoxicity
- Breakdown in vivo to liberate alkylating and carbamylating species
Procarbazine
- CCNS
- Decreases DNA, RNA and protein synthesis
- Inhibits transition from G1 to S phase
Dacarbazine (DTIC)
Temozolomide
- CCNS
- Methylate DNA and RNA
- Prevents transcription and translation
Platinum Drugs:
- Cisplatin
- Carboplatin
- Oxaliplatin
- CCNS
- Binds to guanine in DNA forming crosslinks
- Interferes with DNA replication and mitosis
- Triggers apoptosis
- S/Es: Decreased BM, nephrotoxicity, peripheral neuropathy, ototoxicity
- Must check kidney function
- Tx with loop diuretics (furosemide)
Anthracyclines:
- Doxorubicin
- Daunorubicin
- CCNS
- Inhibits transcription and replication
- Blocks topoisomerase II
- S/E: Cardiotoxicity
- May be prevented by dexrazoxane
Epipodophyllotoxins:
- Etoposide
- Tenopside
- Kills in S and G2 phases
- Forms ternary complex with DNA and topoisomerase II
- Causes breakage of DNA strands
Camptothecin Analogs:
- Camptothecin
- Topotecan
- Irinotecan
- Act in S phase
- Irinotecan is a prodrug
- Binds to the topoisomerase I and DNA complex
- Prevents DNA replication
- Severe diarrhea possible
Bleomycins
- Active in G2 phase
- Bind to reduced iron in cells and lead to free radical production
- S/Es: Pulmonary fibrosis, pneumonitis, cutaneous reactions, low grade fever, minimal BM suppression
Dactinomycin
- CCNS
- Prevents DNA transcription
- Most potent known
- S/Es: Oral and GI ulceration, stomatitis
Folic Acid Analogs:
- Methotrexate (MTX)
- Trimetrexate (lipid soluble)
- Pemetrexed (multitargeted)
- Active in S phase
- Blocks the biosynthesis of purines
- Decreases DNA synthesis
- S/Es: Oral and GI ulceration, hepatotoxicity, pulmonary toxicity
Leucovorin
- Administered 24-36 hrs after MTX
- Bypass the metabolic block of MTX
Fluorouracil
- CCNS
- Decreased DNA synthesis
- S/Es: Oral and GI ulceration; stop at earliest signs of stomititis and diarrhea
Cytarabine
- Active in S phase
- Inhibits DNA polymerase alpha
- Oral ucleration
Gemcitabine
- CCNS
- Inhibits DNA synthesis
What is the active form of 5-FU? What does it inhibit?
- 5-FdUMP
- Inhibits action of thymidyate synthase
Mercaptopurine (6-MP)
- Inhibits synthesis of adenine and guanine
- Acts at S phase
- Metabolism inhibited by allopurinol
- S/Es: Cholestasis; oral and intestinal ulcers
Thioguanine (6-TG)
- Acts in S phase
- Inhibits synthesis of purines
Adenosine Deaminase Inhibitors:
- Pentostatin
- Cladribine
- Fludarabine
- Inhibit adenosine deaminase
- Decreases DNA synthesis
Vinca alkaloids:
- Vincristine
- Vinblastine
- Vinorelbine
- Acts in M-phase
- Bind to soluble tubulin, blocks polymerization and arrests cellular mitosis in metaphase
- S/Es: Peripheral neuropathy, alopecia, nephrogenic SIADH
Yew alkaloids:
- Paclitaxel
- Docetaxel
- Acts in M phase
- Prevents microtubule depolymerization, cells are arrested in late G2 or M phase
- S/Es: Peripheral neuropathy = dose limiting
L-Asparaginase
- Catalyzes conversion of L-asparagine
- Inhibits RNA and DNA synthesis
- S/Es: Increased risk for thrombosis, impaired liver function, kidney or CNS.
Mitotane
- CCNS
- Blocks hormone production by the adrenal gland
- Destroys adrenal and cancer cells
- S/Es: Fatigue and nausea
Interferons
- CCNS
- Inhibits tumors by regulating the host immune system of the pt
- Slows G1–>S; S–>G2
Prednisone
- Anti-inflammatory
- Apoptosis in certain leukemic cells
Progestins
-Used in hormone responsive cancers expressing progesterone receptor
Tamoxifen, Toremefine
- Antiestrogens
- Used in estrogen receptor positive breast cancer.
Anti-androgens
- Blocks androgen-induced growth
- Normally combined with leuprolide or other luteinizing hormone releasing hormone agonist
- Anti-androgens + leuprolide = total androgen ablation
Bevaczimab
-Blocks VGEF and prevents angiogenesis
Denusomab
-Blocks RANK-RANKL in bone
Trastuzumab
-Blocks Her2/C-Neu
Ipilimumab
- Blocks CTLA4
- S/Es: Colitis
Tremelimumab
- Blocks CTLA4
- S/Es: Diarrhea, colitis, skin rash
Nivolumab
- Blocks PD-1
- S/Es: Fatigue, colitis, skin rash
Pembrolisumab
- Blocks PD-1
- Fatigue, skin rash
Imatinib
Blocks Bcr-Abl Kinase
Erlotinib, Gefitinib
-Blocks EGFR signaling
Crizotinib
-Blocks ALK-1 kinase
Amirubicin
- Anthracyline
- Reduced cardiotoxicity
Fulvestrant
- ER blocker
- Lacks partial estrogen activity
- Useful for estrogen responsive cancers
Abraxane
- IV nanoparticle
- Albumin bound formulation of paclitaxel
- Cremophor-free
Picoplatin
- Organic platinum containing
- Does not cause platinum resistance
