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148 Cards in this Set

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Surgery - Localized or Systemic Treatment?
Localized
Radiation - Localized or Systemic Treatment?
Localized
Biologic Tx - Localized or Systemic Treatment?
Systemic
Chemotherapy - Localized or Systemic Treatment
Systemic
What does Adjuvant mean?
Means treating secondary to surgery.
What is Neoadjuvant therapy and what does it entail?
It is shrinking the tumor prior to removal and entails reducing the tumor burden.
What is Adjuvant Chemotherapy and what does it entail?
It is eradicating micrometastases following a localized treatment. Potentially cures the patient.
Vincristine, vinblastine, vinorelbine, paclitaxel, docetaxel work during which phase of the cell cycle?
M - Mitosis
Mustard agents such as carmustine, lomustine work during which phase of the cell cycle?
G0 - Dormant phase
Methotrexate, Cytarabine, 5-FU, Fludarabine, hydroxyurea affect which part of the cell cycle?
S phase - DNA synthesis
CCS agents have which type of cytotoxicity, dose dependent or schedule dependent?
Schedule dependent
CCNS agents have ______ dependent cytoxicity.
Dose
Which phase of the cell cycle is the shortest?
M phase (Mitosis)
What are the two purine bases?
Adenine and Guanine
How do anti-metabolites work?
Replacing metabolites in DNA/RNA replication molecules to inhibit DNA/RNA function or synthesis.
5-FU: Class?
Fluorinated Pyrimidine: Antimetabolite
5-FU: MOA
Converts to FdUMP which binds to thimydilyate synthase, which is required for DNA synthesis.
Purpose of Leucovorin for 5-FU?
Stabilizes FdUMP-TS complex.
5-FU ADR (4 major)
Mucositis, Diarrhea, stomatitis, Hand and foot syndrome.
What happens when you give a bolus dose of 5-FU ADR wise?
Neutropenia, less of the other ADRs
Cepecitabine- Class
Fluorinated Pyrimidine -Antimetabolite
Cepectitabine - MOA
Prodrug of 5-FU, therefore same as 5-FU
Cepecitabine - ADR
Diarhea, mucositis, stomatitis, hand-foot syndrome
How is Capecitabine/Xeloda dosed?
Dosed every 12 hours to produce similar profile as 5-FU continuous
Cytarabine - Class
Cytidine Analog-Antimetabolite
Cytarabine- MOA
Penetrates cells via carrier, is phosphorylated to ara-CTP that inhibits DNA polymerase (strang elongation)
Also encorporates and acts as chain terminator.
Cytarabine- ADR
Neurotoxicity, Conjunctivitis but only with 2-3g/m3 high dose Tx
How do you manage the ADR's associated with high dose Cytarabine
Assess w/ neuroexam and Px with steroids for chemical conjunctivitis (2 drops OU BID)
Gemcitabine/Gemzar - Class?
Cytidine Analog- Antimetabolite
Gemcitabine/Gemzar- MOA
Inhibits DNA Polymerase
Inhibits Ribonucleotide reductase to prevent conversion to deoxy form
Penetrates cells better than Ara-C
Protected from strand excision
Azacitidine-Class
Cytidine analogs-antimetabolites
Azacitidine/Vidaza-MOA
Promotes hypomethylation of DNA causing direct toxicity, promotes maturation of normal cells.
Used for Myelodysplastic syndrome.
Gemcitabine major ADR
Thrombocytopenia
Fludarabine/Fludara-Class
Purine antimetabolite
Fludarabine ADR
Myelosuppression/Immunosuppression
How do you manage the side effects associated with Fludarabine?
Px as though they are HIV+
Give PCP px, Anti-viral Px and Fungal Px
Methotrexate/MTX - MOA
Inhibits DHFR
What is the rescue for MTX?
Leucovorin.
How do you prevent leucovorin from saving cancer cells from the MTX Tx?
Delay about 24 hours, monitor levels closely.
MTX-ADR's
Mucositis, Neurotoxicity, NEPHROtoxicitiy (Give IV hydration, Alk urine)
Pemetrexed-MOA
Inhibits TS, DHFR, GARFT, AICARFT
Primary use of Pemetrexed
Lung and Mesothelioma
Pemetrexed-ADR
Skin Rash, Fatigue, Myelosupression
How do you combat the Skin rash associated with Pemetrexed?
Dex 4mg BID x 3 days, beginning day prior to the dose.
What other regimens are necessary to combat ADR's of Pemetrexed besides Dex?
Folic acid or MVI with folic acid 350mcg to 1000mcg QD 5-7 days before treatment, during and for 21 days after treatment as well as Vit B12 1000mcg IM q 9 weeks
What drugs should be avoided while using Pemetrexed?
Aspirin, NSAIDs due to bleeding risk
Vinblastine, Vincristine and Vinorelbine are considered what type of agents?
Vinca Alkaloids, or Spindle poisons
Vinca Alkaloids - MOA
Bind to tubulin, disrupt normal balance of polymerization of microtubules, inhibts formation of spindle causes arrest in M phase
MAJOR MAJOR Administration restriction regarding Vinca Alkaloids
NO INTRATHECAL!
ADR's common to all Vinca Alkaloids (4)
Extravasation, Myelosuppression, constipation, alopecia
Major ADR associated with Vinblastine in particular?
Bone toxicity (Myelosuppression)
Major ADR associated with Vincristine in particular?
Neurotixicity/Constipation (C for CNS)
Major ADR associated with Vinorelbine in particular?
Middle of road on most ADR's common to vinca alkaloids, however significant myelosuppression.
Paclitaxel-Class
Taxane
Docetaxel-Class
Taxane
Taxane MOA
Bind to tublin without interfering with assembly, however intereres with dissassembly by causing polymerization--> FORMS STABLE BUT NONFUNCTIONAL MICROTUBULES
Px for Taxanes
Benadryl, APAP, Steroid, H2RA
ADR associated with Taxanes
Hypersensitivity, Peripheral neuropathy, Nail changes, Fluid retention
We are are SENSITIVE to Taxes which cause us to bite our NAILS because of the NEUROlogical strain. We also hold WATER.
Etopioside- Class
Topoisomerase inhibitor
Teniposide-Class
Topoisomerase inhibitor
Which drug class is particularly associated with secondary leukemias?
Topoisomerase inhibitors
How do topoisomerase inhibitors work?
They prevent strand rejoining after breakage.
Are Topoisomerase inhibitors CCS or CCNS
CCS
Predominant use of Irinoectan?
Colorectal Cancer
Irinoectan MOA
Inhibits Topo Iso 1
Irinotecan ADR
Diarrhea, Mucositis
Irinotecan ADR Management
Acute diarrhea (50% of patients): Cholinergic rxn, give Atropine.
Late diarrhea (90% of patients), give loperamide. Late phase takes 11 days for onset.
Doxorubicin, Daunorubicin, Idarubicin- Class
Anthracyclines
Anthracycline MOA
Intercalation, Interfere with Topo 2, Free radical formation
Anthracycline ADR
Extravasation, Red secretions, secondary leukemias, CARDIOTOXICITY
What are the risk factors for cardiotoxicity with anthracyclines?
Previous heart irradiation, elderly, very young, females, preexisting uncontrolled HTN, cardiac disease, peak concentrations
What doses of Anthracyclines are associated with Cardiomyopathy, rhythm disturbances for life?
>500mg/m2
Dexrazoxane - MOA
Chelates divalent ions, ferric ion--> prevents free-radical formation, reduces cardiotoxicity associated with AC
What should you consel patients to avoid while taking an Anthracycline?
Antioxidants
Mitoxantrone-MOA
Similar to AC, includes intercalation, less free radical however
Mitoxantrone-ADR
Blue/green secretions, extravasation, myelo, muco... less CARDIO TOXICITY!
Are Alkylating agents considered CCS or CCNS?
CCNS
What 3 drug classes can cause secondary leukemias?
Topo inhibitors, Anthracyclines and Alkylating agents
Why is the fact that alkylating agents are CCNS considered significant?
Cause they only target rapidly reproducing cells.
Cyclophosphamide-Class
Alkylating agent
Cyclophosphamide-MOA
Activated to alkylating metabolites by liver. Forms Acrolein
What is Acrolein and what causes its production and how is it handled?
Acrolein is a inactive metabolite formed by Alkylating agents that causes hemorrhagic cystitis. It is managed by administering MESNA.
Describe the dosing difference between cyclophosphamide and ifosfamide
Ifosfamide is metabolized to active form much slower therefore requires much higher doses, thus has a higher risk of hemorrhagic cystitis.
Cyclophosphamide/Ifosfamide ADR
Neurotoxicity, Hemorrhagic cystitis
How is the neurotoxicity associated with ifofsamide handled?
Give methylene blue
When is MESNA given for ifosfamide?
Given before and at 4 and 8 hours following ifosfamide dose in doses 60-100% of ifosfamide dose. MUST HAVE AT LEAST 60%!!!
Carmustine/Lomustine MOA
Alkylating agents that are lipophilic thus can cross BBB and can be used for tumors of the brain.
Carmustine/Lomustine ADR
Delyaed myelosuppression, phlebitis (Car), NV (Lom), Pulmonary (car)
Cisplatin-MOA
Forms crosslinking between DNA causing distorition, prevents normal base line up.
Cisplatin-ADR
Nephrotoxicity, NV, Ototox, Neuropathy
Treatment and Risk factors for Nephrotoxicity associated with Cisplatin
IVFs and electrolyte replacement (for K,Mg wasting)...
Risk factors: High single dose, Cumulative dose, dehydration, prexisting renal Dz, concurrent renal toxic doses.
Carboplatin-MOA
Same as cisplatin:Forms crosslinking between DNA causing distorition, prevents normal base line up.
Dosing for Carboplatin
Dose=(CrCl+25)xAUC
Typical AUC target 4-8
Carboplatin- ADR
Thrombocytopenia, neutropenia, NV delayed, Nephro (less than cisplatin)
Oxaliplatin-Approval
2nd line metastatic colorectal cancer
Oxaliplatin-ADR
Neurotoxicity (dose limiting, laryngopharyngeal spasms exacerbaetd by cold), NVD
Which agents bind to the extracelluar Tyrosine kinase receptor to prevent binding of a ligand?
Trastuzumab
Which agents are tyrosine kinase inhibitors that prevent transfer of phosphate to prevent cellular proliferation?
Imatininib
Which agent are antibodies that directly induce apoptosis?
Rituximab, alemtuzumab
Whcih agents are antivbodies that are conjugated with toxins/chemotherapy?
Gemtuzumab
CML?
Chronic myeloginous leukemia
Imatinib-MOA
Binds to ATP binding site to inhibit TK, inhibits cellular proliferation and causes apoptosis
Imatinib-Selectivity
BCR-ABL and C-KIT
Major use of Imatinib
CML
Dasatinib-MOA
Similar to Imatinib:Binds to ATP binding site to inhibit TK, inhibits cellular proliferation and causes apoptosis
Imatinib-ADR
Generally well tolerated, myelosuppression
Dasatinib-ADR
Generally well tolerated, myelosuppression
Which agents could be used for Philadelphia chromosome positive ALL?
Imatinib, Dasatinib
Major use of dasatinib
CML/Philadelphia Chromosome positive ALL
Erlotinib MOA
Inhibits EGFR TK, inhibits proliferation and causes apoptosis
Erlotinib use
Lung cancer
Erlotinib-ADR
Rash, pruritis, dry skin, Diarrhea, Conjunctivitis
Sorafenib Use
Renal cancer
Sorafenib MOA
Multikinase inhibitor (Raf kinases and cell surface kinase receptors VEGFR,PDGFR, cKIT)
Sorafenib ADR
Diarrhea, fatigue, HF syndrome
Sunitinib MOA
Multikinase inhibitor
Sunitinib ADR
Fatigue, rash and hair changes, diarrha, decreased LVEF
Sunitinib USE
Renal cell carcinoma and GIST, AML
xxxxNIB usually denotes which class?
Tyrosine kinase inhibitors
Sora and Suni help what?
Renal cancer
Ima and Dasa help what?
CML/Philadelphia
ErLO helps what?
Lung cancer
Trastuzumab/Herceptin MOA
Targets HER2; proto-oncogene that encodes for recepotr protein related to EGFR--> inhibits proliferation of cells that overexpress HER2, aslo stops intracellular signlalling, causes apoptosis
Trastuzumab/Heceptin USE
Metastatic Breast cancer
Trastuzumab ADR
Infusion reactions
Rituximab MOA
Targets CD20 on B-lymphocytes to stop cell cycle
Rituximab USE
Non-hodgkins lymphoma
Rituximab ADR
Hypersensitivity, Infusion rxn (use APAP/Benadryl), hypotension
Ibrotumomab-MOA
Anti-CD20 like Rituximab, however has ytrrium radiotag
Ibrotumomab ADR
Same as rituximab but with 7-9 week delay on myelosuppression
Tositumomab ADR
Same as rituximab but with 7-9 week delay on myelosuppression AND HYPOTHYROID
Tositumomab- MOA
ANTI-CD with radioactive Iodine
Gemtuzumab- MOA
Antitumor ABx attached to humanized anti-CD33 Antibody, causes double strand breaks and inhibits synthesis
Gemtuzumab - USE
AML
Gemtuzumab - ADR
Myelosuppression, HEPATIC DYSFUNCTION
Alemtuzumab- MOA
Targets CD52 on T/B lymphocytes, cause cell lysis
Alemtuzumab USE
CLL
Alemtuzumab ADR
Infusion rxn (APAP/Diph), Immunosuppression requiring Px Abx
Cetuximab-MOA
Binds to EGFR to prevent ligand binding
Cetuximab- USe
Colorectal cancer
Cetuximab-ADRs
Acneform rash. infusion reaction
Bevacizumab/Avastin-MOA
MAB that binds VEGF TO PREVENT ANGIOGENSISI
beVACizumab VACuums up blood vessels preventing__________________
Angiogenesis
Major use of Bevacuzumab
Colorectal cancer
Bevacuzumab ADR
Thromboembolic events, hypertension
How do you calculate BSA in English units?
Square root of: (Ht in x Wt lbs)/3131
How do you calculate BSA in metric units
Square root of: (ht cm x Wt kg)/3600
For which drug is AUC used for dosing
Carboplatin