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Agents that act in G1 phase
Steroids Asparaginase
Agents that act in S phase
What cell cycle phase does etoposide affect?
G2 phase.
What phase of cell cycle do taxanes affect?
M phase
Agents that are not cell cycle specific.
Alkylating Agents, Anthracyclines.
Alkylating Agent. Nitrogen Mustard
Alkylating agent. Nitrogen Mustard
irritant. Alkylating Agent. Nitrogen Mustard.
carmustine (BCNU)
Nitrosourea. Nitrosureas are very lipophillic unlike nitrogen mustard so they can cross the BBB and are useful for CNS tumors.
lomustine (CCNU)
Nitrosourea. Nitrosureas are very lipophillic unlike nitrogen mustard so they can cross the BBB and are useful for CNS tumors.
Alkylating Agent. Platinum analogue. Cuases myleosuppression. Nephrotoxicity, ototoxicity, and neurotoxicity.
Alkylating Agent. Platinum analogue. Less NV, less neruotoxicity, but a lot more myleosuppression.
Alkylating agent. Platinum analogue. Special sensory neuropathy that you don't see with others - intolerance to cold after infusion.
How do antimetabolites work?
Interfere with DNA synthesis by incorporating themselves into DNA.
antimetabolite. Folate antagonist.
antimetabolite. folate antagonist.
antimetabolite. purine analgoue.
antimetabolite - purine analogue.
antimetabolite, purine analog.
Fluorouracil (5-FU)
antimetabolite - pyrimidine analog. Commonly used in a lot of GI cancers. Toxicities are mucositis and diarr, myleosuppression.
Cytrabine (ara-C)
antimetabolite - pyrimidine analog. Used for hematological malignancies, lymphoma, leukemia.
antimetabolite, pyrimidine analog. prodrug to 5-FU. Can take this as an outpatient. Major tox are GI, diarr, and hand foot syndrome. Red swelling painful hands and soles of feet.
antimicrotubules - vinca alkaloids. Neuropathies with vinca alkaloids. sensory and autonomic neruopathies (paraletic illeus)
antimicrotubule - vinca alkaloid. Neuropathies with vinca alkaloids. sensory and autonomic neruopathies (paraletic illeus)
antimicrotubule - vinca alkaloid. Neuropathies with vinca alkaloids. sensory and autonomic neruopathies (paraletic illeus)
antimetabolite - taxane. Causes hypersensitivity so have to premed.
antimicrotubule - taxane.
What are two side effects of docetaxel?
edema and ascities
Irinotecan (CPT-11)
Topo I inhibitor. Causes diar. attenuated delayed diar. Mange it with anti-dia
Topo I inhibitor. CNS tumors, pediatric malign.
Etoposide (VP-16)
topo II inhibitor. Variety of solid tumors.
topo II inhibitor.
antitumor antibiotics
end with -rubicin except for mitoxantrone. These agents are cell cycle nonspecific and are known for their cardiotoxicity.
antitumor antibiotic. causes pulmonary tox
antitumor antibiotic
antitumor antibiotic
cancers that can be CURED with chemo
Acute Lymphocytic Leukemia in children Acute myeloid leukemia Testicular Cancer Hodgkin's Disease Non-Hodgkin's Lymphoma Small cell lung cancer (limited stage)
Malignancies for which chemo is used with curative intent.
Breast cancer (Early stage) Colorectal cancer (Advanced stages) Osteosarcoma Ovarian cancer
Why would you use combination chemothearpy? What are some principles for use?
Drugs with different mechs of action Avoid overlapping tox Drugs with demonstrated activity optimal use of drug ande schedule.
CHOP thearpy
Cyclophosphamide, Hydroxy- daunarubicin, Oncovin, Prednisone – NHL
This factor is over expressed in 50-80% of NSCLC
What type of agent is Leuprolide and what is it used for?
LHRH agonists. prostate cancer
MAID thearpy
Mesna, Adriamycin, Ifosfamide, Dacarbazine – Sarcoma
Hormonal Thearpy for breast cancer treatment
anti-estrogens, aromatase inhibotrs
anti-estrogen. causes: Hot flashes Nausea Fatigue Flare reactions Endometrial cancer Thromboembolic events
anti-estrogen. used for breast cancer
Fulvestrant injection
anti estrogen. used for breast cancer
aromatase inhibitor. used for breast cancer.
aromatase inhibitor. used for breast cancer
Hormonal treatment for prostate cancer treatment
anti-androgens, LHRH agonists
anti-androgens are used for what type of cancer?
what type of drug is flutamide?
what type of durg is bicalutamide?
What type of agent is Goserelin?
LHRH agonists
What is Goserelin used for?
prostate cancer
Immunothearpy Bilogical response modifiers
Malignant melanoma and CML Interferon-alfa-2a (Roferon) Interferon-alfa-2b (Intron) Interferon-alfa-N3 (Alferon) PEG-interferon-alfa-2b (PEG-Intron)
agents used for renal cell carcinoma
Renal Cell Carcinoma Interleukin-2 (IL-2) Aldesleukin (Proleukin)
monoclonal antibodies
end in -mab Gemtuzumab ozogamycin Rituximab Trastuzumab Alemtuzumab Bevacizumab Cetuximab
Limitations to monoclonal antibody thearpy
Large molecules have poor access to bulky tumors Slow distribution Rapid clearance of antibody by circulating tumor cells Immunogenicity (Infusion related/allergic reactions)
Tyrosine Kinase Inhibitors (TKIs)
Small molecule oral agents, intracellular targets
Gefitinib (Iressa)
EGFR Tyrosine Kinase Inhibitor. Thirdline monothearpy metastaic NSCLC
What are 2 common adverse effects to EGFR tyrosine kinase inhibitors?
Diarrhea, acneform rash.
Erlotinib (Tarceva)
EGFR tyrosine kinase inhibitor. second or third line thearpy for monothearpy NSCLC 150 mg PO QD First line treatment with gemcitabine for metastatic pancreatic cancer 100 mg PO QD
Multikinase TKIs adverse effects
diarrhea, nausea, acneform rash, HTN, handfoot syndrome, liver abnormalities.
Suntinib (Sutent)
multikinase TKI. VEGFR, PDGFR, cKIT. GIST after disease prgoression on imatinib. advanced renal cell carcinoma.
Sorafenib (Nexavar)
VEGFR, PDGFR, Raf Advanced renal cell carcinoma 400 mg PO BID
Imatinib (Gleevec)
Inhibits Bcr-Abl protein tyrosine kinase Translocation 9:22 chromosomes Inhibits Kit and PDGFR Indicated for Ph-positive ALL or CML 400-600 mg PO QD Myelosuppression, nausea, diarrhea, fluid retention, myalgias, skin rash, hepatotoxicity
Super Gleevecs
overcome imatinib resistance. Dasatinib (Sprycel) FDA approved June 2006 300 fold more potent than imatinib 700 mg PO BID Myelosuppression, nausea, diarrhea, edema, effusions Nilotinib (Tasigna) FDA approved 10/2007 20 to 50-fold more potent than imatinib Myelosuppression, rash, hyperbilirubinemia
How do oral immunomodulating agents work?
modulation of T helper cells, inhibiton of TNF-alpha, antiangiogenesis
What type of agent is Thalidomide?
oral immunomodulating agent
What is Thalidomide used for?
newly diagnosed multiple myeloma. It is used in combination with dexamethasone
What are the side effects of thalidomide?
teratogenciity, VTE, neutropenia, neruopathy, constipation
What type of agent is lenlidomide
oral immunomodulating agent
What is lenlidomide used for?
MDS with sympotmatic anemia, multiple myleoma
What are the side effects of lenalidomide?
myleosuppression, thrombosis, less neuropathy.
What are the three factors that influence the modality of cancer treatment?
cancer type, prior thearpy, cancer stage
What are five ways cancer can become drug resistant (acquired mechanisms)
Improved proficiency in DNA repair Increase in drug inactivation Decrease in cellular uptake of drug Decrease in drug activation Increase in efflux of drug
What things can be done to help manage drug resistance? (3)
Change Therapies Increase Dose Biochemical modulation
What is biochemical modulation in drug resistance treatment?
Leucovorin + Fluorouracil Cyclosporin and analogues (PSC-833) Calcium channel blockers
What are sanctuary sites?
CNS, Brain, very common with hematological cancers. Depending on thearpy might relapse in the CNS. Testis are another site. Leukomia relapse in testis
How can you overcome sanctuary sites of tumors?
high dose of chemo, high dose of MTX, local administration.
What are 3 considerations for drug scheduling of chemo thearpy?
dose-intensity, cell cycle kineitics and efficacy (what stage the drug works in the cell cycle), toxicity
Name around 7 considerations for chemo that are patient related factors.
Renal and/or Hepatic Function Age/Performance status Prior exposure to chemotherapy Nutritional status (if healthy you will have less myleosuppression) Immunocompetence
What type of agent is Mesna?
How does mesna chemoprotect?
Binds to drug and prevents it from attacking bladder wall.
What type of drug is dexrazoxane?
cardioprotective chemoprotectant
This agent decreases cardiotoxicity specifically related to anthracyclines
What type of agent is amifostine?
chemoprotectant - decreases nephrotox
This agent decreases nephrotoxicity with cisplatin thearpy.
What type of agent is leucovorin?
chemoprotectant - helps replenish folates.
This agent helps replenish folates that are missing because of MTX. It also helps alleviate mucositis and myleosuppression.
What is myelosuppression?
suppression of RBC (anemia), WBC (granulocy) and platelts (thromobocytopenia)
Granulocytopenia is defined by these two lab values
neutropenia - ANC< 500/m3 Fever > 38.3
Name around 6 causes of nausea and vomitting
Causes of emesis: Chemotherapy, radiation, surgery Other Drugs Obstruction Gastritis/Esophagitis Brain Metastasis Pancreatitis
These factors infleunce emetic potential
Drug, Dose, Schedule Prior Emetic Experience - Anticipatory N/V Alcohol Use Gender Age
Do alcohol abusers do better or worse with N/V?
abusers do better with N/V
Do females do better or worse with N/V?
Females do worse.
Name 8 N/V drug thearpies
5-HT3 receptor antagonist Substitued Benzamides (metoclopramide) Phenothiazines (prochlorperazine) Butyrophenones (haloperidol) Corticosteroids (dexamethasone) Benzodiazepines (lorazepam) Cannabinoids (dronabinol) NK-1 antagonists - Aprepitant (Emend)
What type of agent is prochlorperazine?
N/V agent
What type of agent is metoclopramide?
N/V agent
5-HT3 receptor antagonists are useful for what?
What type of agents are NK-1 antagonists?
N/V agents
what type of agent is aprepitant?
NK-1 antagonist or N/V drug thearpy
What is megestrol acetate used for?
What are corticosteroids used for?
anorexia AND N/V
what are anabolic steroids used for?
What is fluoxymesterone used for?
What is Nandrolone decanoate used for?
What types of infections cause mucositis?
HSV, fungal.
Why should mucositis legions be cultured?
to r/o viral or fungal
What types of chemo cause mucositis?
fluorouracil, MTX, antracyclines.
What is the etiology of mucocitis?
radiation, chemo, infection
What factors infouence severity of mucositis?
drug, dose, schedule
HOw should mucositis be managed? (five thigns)
General mouth care Decreased oral intake nutritional supplements parenteral nutrition Pain management Antiviral therapy Antifungal therapy
What causes diarrhea in cancer patients?
chemo, infection.
What are some complications from diarrhea? (3)
Fluid and electrolyte imbalance Peri-rectal cellulitis Anorexia
What kind of agent is loperamide?
What kind of agent is Diphenoxylate/atropine?
What is a major toxicity of Doxorubicin?
cardiac tox
What are some risk factors for cardiotox due to doxorubicin? (5)
Cumulative dose > 550 mg/m2 Schedule of Administration Age Prior radiation therapy to chest Pre-existing cardiac disease
What is a major tox of bleomycin?
pulmonary toxicity
What are the risk factors for pulmonary toxicity from bleomycin? (3)
cumulative dose > 450 units Pneumonitis, interstitial fibrosis Other drugs causing pulmonary fibrosis Busulfan Carmustine Chlorambucil
Name 3 drugs that can cause pulmonary fibrosis, and thus are risk factors for pulmonary tox with bleomycin.
Busulfan Carmustine Chlorambucil
This drug can cause renal tubular necrosis.
This drug causes renal tubluar obstruction
methotrexate (MTX)
These two drugs cause hemmoragic cystis.
How can you help tubular necrosis?
Hydration osmotic diuretic like mannitol.
How can you help MTX tox?
give sodium bicarb to alkalinze the urine and help eliminate MTX.
What two types of agents cause neruopathies?
vinca alkaloids, platinum
What agent causes cerebellar tox??
This agent causes ototox
cremophor EL is used for what?
hypersensitivity rxns.
What are some late effects of alkylating agents? (s)
What is a late effect of tamoxifen?
uterine cancer
What type of secondary malignancy is due to a late effect of cyclophosmamide/ifofamide?
what type of secondary malignancies are due to radiation?
sarcoma, leukemias
These 3 chemothearpy agents cause the late effect of infertility
cytoxan, nitrosureas, procarbazine
list the people who will have a greater effect on infertility (ie sex etc). order great from least
adult men > postpubertal women > prepubertal women
What phase of the cell cycle do Vinca Alkaloids affect?
M phase
what type of drug is nilutamide?
What are 3 side effects of anti-androgens?
gyencomastia, increased LFTS, diarrhea.
What are LHRH agonists used for?
prostate cancer
Name 3 side effects of LHRH agonists
hot flashes, tumor flare, impotence
What should docetaxel be premed with and why?
dexamethasone b/c edema is thought to be due to inflamm process
Mechanism of action of topoisomerase inhibitors
prevent DNA uncoiling
Mechanism of alkylating agents
interfere with DNA base pairing, leading to the strand breaks and arresting DNA replication
Mechanism of action of Taxanes and vinca alkaloids
Interfere with microtubule function required for cell mitosis
Mechanism of action of antimetabolites
block the formation and use of nucelic acids essential for DNA replication
CD20 is overexpressed on what types of malignant and normal tissues (2)
lymphoma and leukemia cells
HeR2/neu is present on 25% of what type of cancer cells?
breast cancer cells
VEGFR is overesxpressed on what types of malignant and normal tissues?
tumor vasculature
How can receptor pathways of cancer cells be inhibited? (4)
binding and neutralizing ligands occupying receptor-binding sites blocking receptor signaling within the cancer cell interfering with downstream intracellular molecules
What are some common side effects of G-CSFs? (4)
mild to moderate bone pain fever generalized rash injection site redness
What is the indication for Pegfilgrastim
Decrease the incidence of infection in patients with non-myeloid malignancies receiving chemotherapy associated with a significant incidence of febrile neutropenia.
What are some adverse effects of Pegfilgrastim (4)
bone pain splenic rupture adult resp distress syndrome sickle cell disease
What is Darbepoetin alfa?
A novel erythropoiesis-stimulating protein with two extra sialic acid-containing carbohydrate side chains.

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