Term
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Definition
| mutant, rapidly dividing cells with no proliferation restriction |
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Term
| the goal in treating cancer is to... |
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Definition
| eradicate 100% of the tumors |
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Term
| DNA synthesis happens in which phase? |
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Definition
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Term
| Mitosis happens in what phase? |
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Definition
|
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Term
| cancer protocol includes: |
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Definition
| intermittent infusions of multiple agents in order to affect diff. growth stages or mech. of actions WITHOUT overly suppressing the bone marrow |
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Term
| Tumors are not visible on X-Ray until... |
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Definition
| it reaches 100 million cells |
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Term
| Tumors are not palpable until... |
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Definition
| it reaches about 1 billion cells |
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Term
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Definition
| there are 1-100 trillion cancer cells |
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Term
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Definition
| If cancer tx doesn't fully eradicate the cancerous cell, it is possible to leave only one cell and have a relapse of cancer.
You can plot data (# of cancer cells on a log scale vs. time) to find of the tx is killing enough C cells each round |
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Term
| Rapidly growing tumor cells spend a large amt. of time in which phase(s)? |
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Definition
| S & M phases. "Growth fraction" |
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Term
| Cell cycle specific (CCS) means what? |
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Definition
| They are schedule-dependent and only work in their respective phases (i.e M or S phase) |
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Term
| In slower growing tumors, most cells are in which phase? |
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Definition
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Term
| Cell cycle non-specific (CCNS) means what? |
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Definition
| They will be effective regardless of cell cycle or phase.
Their efficacy is limited only by dose, and therefore are dose-dependent |
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Term
| Alkylating Agents - properties/SE |
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Definition
*CCNS (works on DNA)
*highly emetogenic
*Vesicant
*Mutagenic (rare)
*Myelosuppressive
*Given on intermittent schedule to all WBC count to rebound. Dose/therapy limiting. |
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Term
| What to do if drug is emetogenic? |
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Definition
| Premedicate with Zofran, Kytril, Ativan, or Reglan |
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Term
| What can happen with drugs that are vesicants? |
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Definition
| It is a blistering agent. If extravasation occurs, they cause blistering and killing of the tissue. |
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Term
| Why would an alkylating agent be mutagenic? |
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Definition
| They chemically modify the DNA to destroy the cancer. This can happen in normal cells as well, and cause a different kind of cancer after tx. |
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Term
| What are two types of Alkylating agents? |
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Definition
| Nitrosureas & Nitrogen mustards |
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Term
| Name three Nitrosurea drugs |
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Definition
1. Carmustine (BCNU)
2. Lomustine (CCNU)
3. Semustine (methyl-CCNU) |
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Term
| Name two types of Nitrogen Mustard drugs |
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Definition
1. Cyclophosphamide (Cytoxin)
2. Ifosfamide |
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Term
| What does it mean when a drug is myelosuppressive? |
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Definition
| All anti-neoplastic drugs kill some amount of bone marrow b/c it is composed of fast growing cells - each drug varies in its degree, however.
Because of this, a pt will have leukopenia, neutropenia, and/or thrombocytopenia |
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Term
| What is one of the main advantages of Carmustine? |
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Definition
| It's CNS concentration is 50% of plasma levels.
So, it can be made into wafer form (Gliadel) and implanted into the the cavity made when a brain tumor is removed.
The wafers degrade slowly, distributing Carmustine over 2-3 weeks.
Gliadel is approved for tx of malignant brain cancers (ex: glioblastoma). |
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Term
| What is the main side effect of Nitrogen Mustard drugs, and how can it be prevented? |
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Definition
| Both Cytoxin and Ifosfamide have to be activated by CYP450, but in doing so acrolein, which is v. toxic to kidney/bladder, is formed and can cause hemorrhagic cystitis.
Prevention:
*Vigorous hydration: Infuse 1L NS before and during chemo tx.
*Mesna is a cpd. that neutralizes acrolein. Give scheduled does before and several times after infusion. |
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Term
Toxicities specific to Nit. Mustards:
(besides the ones shared with all alkylating agents) |
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Definition
| alopecia, mucosal ulcerations (i.e. mouth, GI |
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Term
| What are three types of Platinum Coordination Complexes? |
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Definition
1. Cisplatin
2. Carboplastin
3. Oxilliplatin |
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Term
| Name three of the Platinum Coordination Complexes |
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Definition
1. Cisplatin
2. Carboplastin
3. Oxiliplatin |
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Term
| Platinum Coordination Complexes major toxicities |
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Definition
1. Renal toxicity
2. Ototoxicity
3. PROFOUND nausea & vomiting
4. Electrolyte disturbances |
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Term
| What makes Oxiliplating preferred over the other PCC drugs? |
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Definition
| It's a third gen. of Cisplatin and has fewer adverse effects |
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Term
|
Definition
1. Highly protein bound (esp. Cisplatin)
2. It's renally excreted, accumulation causes toxicity so be sure to adequately hydrate
3. Oxiliplatin has a v. lrg. Vd so it can cross membranes easily and reach more tumors |
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Term
| In Cisplatin gel, what is the role of epi & collagen? |
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Definition
| This gel is being developed for direct injection into solid tumors. The epi provides local vasoconstriction (to dec. sys. response) and the collagen keeps all the material together. |
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Term
| Antimetabolites work on what phase of the cell cycle? |
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Definition
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Term
| What is the relationship btwn Methotrexate (MTX) and Leucovorin? |
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Definition
| MTX is cytotoxic to all rapidly dividing cells.
Leucovorin is given at timed intervals during MTX therapy so that normal cell will take it up (instead of the MTX?) and 'side-step' toxicity. |
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Term
|
Definition
1. Myelosuppresion/thrombocytopenia
2. GI tract ulcerations |
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Term
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Definition
1. 90% renal excretion (this is why pts are susceptible to renal fail.)
2. 'Saturable absorption from GI tract' - there is a ceiling to how much drug is absorbed b/c there is a finite amt of transporters in the body |
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Term
| Name the drugs in 4 subcategories of the Antimetabolites |
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Definition
1. Methotrexate (MTX)
2. Fluorouracil & Capecitabine
3. Cytarabine, Fludarabine, & Gemcitabine
4. 6-Mercaptopurine (6-MP) & 6-Thioguanine (6-TG) |
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Term
| Fluorouracil & Capecitabine mj toxicities: |
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Definition
1. myelosuppression/thrombocytopenia
2. alopecia |
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Term
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Definition
*It is a prodrug of fluorouracil
*80% bioavailability and can be administered as a tablet
*Required enzyme for bioactivation to fluorouracil is expressed very high in the cells of solid tumors (compared to NL cells)
*Fun fact: Fluorouracil is used as a topical cream for psoriasis |
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Term
| Cytarabine, Fludarabine, & Gemcitabine mj. toxicities: |
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Definition
1. leucopenia
2. thrombocytopenia
3. anemia
4. GI problems
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Term
|
Definition
| Activated to AraCTP by nucleotide kinases (adds phosphates).
AraCTP then competes with dCTP for incorporation into DNA, where it will inhibit DNA polymerase.
AraC is *highly* S-phase specific and should be run in by continuous IV infusion for max exposure |
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Term
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Definition
| 6-MP is metabolized by xanthine oxidase, therefore *major* drug interaction with xanthine oxidase inhibitor (ex: allopurinol - a chemo pt would be on this to decrease the uric acid burden post tumor kill) |
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Term
| Name four sub-categories of the Plant Alkaloids & Antitumor Abxs. |
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Definition
| 1. Vinca Alkaloids (Vincristine, vinblastine, vindesine, vinorelbine)
2. Epipodophyllotoxins (Etoposide/VP16, Teniposide)
3. Camptothecin Analogs (Topotecan, Irinotecan)
4. Taxanes (Paclitaxel, Docetaxel) |
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Term
| Vinca alkaloids mj toxicities: |
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Definition
1. Myelosuppresion
2. Neurotoxicity = perpheral/central neuropathy and cognitive decline
(neurotx stems from axonal transport, wh. interferes w/microtubule formation) |
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Term
| Vinca alkaloids are CCS for... |
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Definition
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Term
| Epipodophyllotoxins are primarily CCS for... |
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Definition
|
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Term
| Etoposide & Teniposide mj toxicity: |
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Definition
|
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Term
| Etoposide & Teniposide mech. of resistance |
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Definition
*P-glycoprotein
*mutations in Topo-II that don't allow the drug to bind |
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Term
| Etoposide & Teniposide PK: |
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Definition
these agents are highly protein bound... what is the influence of plasma albumin levels?
(?) less albumin, more free drug |
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Term
| Topotecan & Irinotecan are CCS for... |
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Definition
|
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Term
| Topotecan & Irinotecan mj. toxicities |
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Definition
1. myelosuppression
2. SEVERE GI complications (dose-limiting) - profound loss GI epithelial cells cause diarrhea, etc. |
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Term
| Taxanes (Paclitaxel, Docetaxel) are CCS to... |
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Definition
|
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Term
| Paclitaxel & Docetaxel PK |
|
Definition
| Have limited solubility and must be delivered in an ethanol/castor oil vehicle = high sensitivity rxns.
Pretx w/ dexamethasone and antihistamines |
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Term
| Paclitaxel & Docetaxel mj. toxicities: |
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Definition
1. myelosuppression
2. peripheral neuropathy (r/t altered microtubules, like with the vinca alkaloids)
3. hypersensitivity rxns (from the ethanol/castor oil) |
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Term
| Anthracycline Abx (5 types) |
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Definition
1. doxorubicin (adriamycin)
2. daunorubicin
3. valrubicin
4. epirubicin
5. Idarubicin
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Term
| Anthracycline Abx mj. toxicities |
|
Definition
1. myelosuppression
2. GI ulcerations
3. Cardiotoxicity*
4. Radiation recall rxn
*Cardiotoxicity is assoc. w/ cumulative doses (550mg/m2). Causes CHF unresponsive to Dig therapy. |
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Term
| Anthracycline Abx produce ROS, why is this important? |
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Definition
| Reactive Oxygen Species (ROS) is a free radical.
Any cell w/ inc. mitochondria (i.e. inc. heme & iron- like the HEART) will throw off free radicals. This is the cause of cardiotoxicity. |
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Term
| With the Anthracycline Abx agents, what can be done to prevent ROS induced cardiotoxicity? |
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Definition
| *Tx with the iron-chelating agent, dexrazoxane. It 'cages' iron, making it inactive so it can't participate in redox (free radical) rxns.
*Dexrazoxane is primarily used in breast CA pts who have met cumulative dose. (Will need baseline EKG & Echo)
*Dexrazoxane does NOT decrease efficacy of doxorubicin |
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Term
|
Definition
| Bleomycin is inactivated by bleomycin hydrolase, which is found in liver, spleen, and bone marrow = reduced toxicity in these areas.
HOWEVER, the hydrolase is NOT present in skin & lung, which is where the Bleomycin toxicity manifests. |
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Term
|
Definition
| 1. VERY LITTLE myelosuppression
2. Cutaneous toxicity
3. Pulm toxicity*
*O2 will form ROS, so do not exceed 30% FiO2 b/c it will potentiate toxicity |
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