onc 7
Terms
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- Induction therapy
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- when the tumor is known to be sensitive
- when the feasibility of surgical removal or radiation destruction of the main tumor mass is poor - G1 drugs
- - steriod hormones
- M drugs
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- vinca alkyloids
- paclitaxel - G2 drugs
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- bleomycin
- podophyllotoxins - S drugs
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- antimetabolites
- podophyllotoxins - CCNS drugs
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- alkylating agents
- most antibiotics - Myelosuppression in chemo
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- WBC decrease and thrombocytopenia the limiting factors
- G-CSF and GM-CSF being used to accelerate BM - antinemetics
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- agents that affect receptors for NT dopamine (D2) and serotinin (5-HT), which trigger N and V
– 5-HT3 receptor antagonists (Ondansetron)
- dopamine D2-receptor antagonists (prochlorperazine, metoclopramide) - most common 2nd malignancy from chemo
- AML
- Alkylating agents - mechanism
- alkylate DNA and cause DNA cross-linking, impairing DNA replication
- alkylating agents - toxicity
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- myelosuppression, except cisplatin with renal toxicity
- N and V - alkylating agents - resistance
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- inc repair, dec perm, inc production of glutathione, an inactivator
- if a tumor is resistant to one alkylating agent, it will also be relatively resistant to others - Cyclophosphamide
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- alkylating agent
- nigrogen mustard
- a prodrug, requiring activation by hepatic cytochrome P450 oxidase - Nitrosoureas
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- alkylating agent
- High lipid solubility facilitates CNS entry
- used for brain tumors - Cisplatin
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- alkylating agent
- inorganic metal complex
- low myelosuppression with cisplatin, instead, renal toxicity - Antimetabolites - chemistry
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- synthetic structural analogs of normal cellular components required for DNA synthesis
- CCS - S phase - Antimetabolites - toxicity
- myelosuppression
- Antimetabolites - resistance
- altered target, decrease in activating enzyme, decreased intracellular concentration
- Methotrexate
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- Antimetabolite
- antagonist of folic acid
- blocks DHFR
- Leucovorin “rescue†(folinic acid admin) can overcome enzyme block and overcome some toxicity
- resistance due to dec drug uptake, mutant DHFR, inc DHFR expression - Purine analougs
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- Antimetabolite
- 6-MP and 6-TG
- require intracellular conversion by HGPRT to 6-TIMP and dTGTP
- resistance usually decreased HGPRT activity - 5-Fluorouracil
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- antimetabolite
- pyrimidine analoug
- inhibits thymidylate synthase and leads to thymineless death by blocking DNA synthesis
- activated to 5-FdUMP - ara-C
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- antimetabolite
- pyrimidine analoug
- inhibits DNA polymerase and DNA synthesis
- activated to Ara-CTP - Plant Derivatives for chemo
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- CCS, inhibition of mitotic spindle function
- cause myelosuppression, except vincristine (peripheral neuropathy) - Vinca alkaloids
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- plant alkyloid
- Vinblastine and Vincristine
- CCS (M-phase) bind tubulin
- vincristine causes peripheral neuropathy - Podophyllotoxins
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- plant alkyoid
- Etoposide
- CCS (S/G2), binds and inhibits topoisomerase II religation, resulting in DNA strand breaks - Taxanes
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- plant alkyoid
- Paclitaxel
- bind to tubulin, but promotes polymerization of microtubules - Antibiotics for chemo
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- natural compounds isolated from soil fungus streptomyces
- CCNS - Anthracyclines
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- Antibiotic
- effects topoisomerase II
- causes myelosuppression - also irreversible cumulative cardiac toxicity - Bleomycins
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- Antibiotic
- unlike other antibiotics, CCS (S) , binding to DNA, causing DNA strand breaks by oxygen radical formation
- pulmonary toxicity
- not MDR - hormones and chemo
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- sex hormones stimulate the proliferation of certain tissues
- Lack of severe toxicity to normal tissue - Tamoxifen
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- hormone
- binds estrogen receptor in G1
- confined to palliative treatment of estrogen-dependent, estrogen receptor positive breast cancers - Gonadotropin-Releasing Hormone Agonists
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- hormones
- Leuprolide and Goserelin are analogs of GnRH
- treatment leads to downreg of receptor and loss of stimulation
- redueces testosterone a lot - Hydroxyurea
- - CCS (S-phase) inhibits ribonucleotide reductase
- L-Asparaginase
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- converts blood asparagine to aspartic acid for Inhibition of protein synthesis
- can casue allergic reaction - Trastuzumab (Herceptin®)
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- humanized monoclonal Ab that recognizes HER2
- HER2 overexpression is correlated with poor patient prognosis in breast and ovarian cancers
- mild toxicity
- use for breast cancer - Gefitinib (Iressa®)
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- protein tyrosine kinase inhibitor
- Inhibits EGFR/HER1 R TK
- used for lung cancer
- causes rash and diarrhea
- 10% response rate for NSCLC - Erlotnib (Tarveca)
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- Inhibits EGFR/HER1 R TK
- used for Lung And Colon Cancers
- causes rash and diarrhea - Cetuximab (Erbitux®)
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- humanized monoclonal Ab
- Inhibits EGFR/HER1 R TK
- used Colon Cancers
- causes rash and diarrhea
- a 10.8% response - growth delayed by 1.5 months
– if used w/ irinotecan, 22.9% response and growth delayed by 4.1 months - Imatinib (Gleevec®)
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- Inhibition Of The BCR-ABL Tyrosine Kinase on Ph chrom
- used CML and GIST
- Resistance due to mutation of BCR-Abl - Bevacizumab (Avastin®)
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- Inhibition of VEGF Receptor Tyrosine Kinase Activation
- used for Tumor Angiogenesis
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