Reading...
Play button
Play button
Use LEFT and RIGHT arrow keys to navigate between flashcards;
Use UP and DOWN arrow keys to flip the card;
H to show hint;
A reads text to speech;
111 Cards in this Set
- Front
- Back
|
cell cycle
|
mitosis: vinca alkaloids, taxanes
DNA synthesis: anti metabolites and epipophyllotixins, camptothecins |
|
|
enzymes responsile for replication
|
topoisomerases, polymerases
|
|
|
Alkylating agents
|
non cell cycle specific, will work in many diff areas, all have similar mechanism of action
Cyclophosphamide* (CTX, Cytoxan®) Ifosfamide Platinums Cisplatin (CDDP) Carboplatin Oxaliplatin Nitrosureas Lomustine* (CCNU) Carmustine (BCNU) **be familiar with the above thy are the most common** Mechlorethamine Melphalan* (Alkeran®) Chlorambucil* (Leukeran®) Busulfan* (Myleran®) Thiotepa Procarbazine* Dacarbazine (DTIC) Temozolamide* *oral |
|
|
Alkylation
|
action focused on nitrogen...adds alkyl group to guanine and creates an alkylated base that prevents DNA from being stable
template being replicated is mesread or mispaired, crosslinking prevents DNA strands from unwinding, single or double strand breaks in DNA occur |
|
|
Mechanism for Cyclophosphamide
|
Parent drug (must be converted) is converted by hepatic microsomal enzymes to 4-hydroxycyclophosphamide (4-HCP)
4-HCP is converted to acrolein (hemorrhagic cystitis) and phosphoramide mustard Phosphoramide mustard alkylates DNA Acrolein is responsible for causing hemorrhagic cystitis must considder liver function and other drugs involving the liver |
|
|
Mechanism of Ifosfamide
|
Parent drug is converted to acrolein and ifosforamic mustard
There is more acrolein formed with ifosfamide Acrolein is responsible for causing hemorrhagic cystitis |
|
|
Toxicities with Cyclophosphamide and Ifosfamide
|
Cyclophosphamide
Myelosuppression Hemorrhagic cystitis Nausea & vomiting Alopecia Syndrome of inappropriate anti-diuretic hormone (SIADH)-->causes incr seizure risk, must hydrate Ifosfamide Hemorrhagic cystitis Myelosuppression CNS toxicity Nausea & vomiting Alopecia Pulmonary & cardiac toxicity |
|
|
Hemorrhagic Cystitis
|
Caused by accumulation of acrolein
Binds to thiol in bladder wall Hematuria, urinary frequency & irritation Prevent with vigorous hydration (≥2 L/day) & MESNA Treat with bladder irrigation, alum irrigation, and other therapies Heme test urine while on therapy |
|
|
MESNA
mercaptoethane sodium |
Uroprotectant containing sulfhydryl group
Binds to acrolein in the bladder to form a nontoxic compound Not systemically absorbed so does not interfere with cytotoxic activity Use with cyclophosphamide >2 g/m2/dose, ifosfamide ALWAYS Effective in prevention only not always given esp if dose is low--not for cancer |
|
|
Platinums
|
Cisplatin, Carboplatin, Oxaliplatin
|
|
|
Cisplatin
|
Filtered by glomerulus & concentrated in renal tubules; incompletely cleared
Nephrotoxicity – ↓ GFR, electrolyte losses (Mg, K), and renal failure Prevent with aggressive hydration (NaCl) |
|
|
Carboplatin
|
Not concentrated in the renal tubules; more efficiently cleared
Dosing based on area under the curve (AUC) Dose = AUC ( GFR + 25 ) |
|
|
Toxicities with Cisplatin, Carboplatin and Oxiplatin
|
Cisplatin
Vomiting Nephrotoxicity Peripheral neuropathy Neurotoxicity Ototoxicity Carboplatin Myelosuppression Neurotoxicity Vomiting Oxaliplatin Peripheral neuropathy** induced by cold** cold drinks can paralyze GI tract Myelosuppression |
|
|
Amifostine (ethyol)
|
chemoprotectant agent that is metabolized to an active free thiol which binds to cisplatin and prevents damage to normal tissue
free radical scavenger side effects include hypotension and nausea and vomiting also used to prevent radiation-associated xerostomia given in radiation therapy for head and neck tumors to prevent xerostomia |
|
|
Oral Alkylating agents
|
Chlorambucil (Leukeran)
Busulfan (Myleran) **Melphalan (Alkeran) Temozolomide (Temodar) |
|
|
Chlorambucil (Leukeran)
|
Used for the treatment of chronic lymphocytic leukemia
|
|
|
Busulfan (Myleran)
|
Used for treatment of leukemia and transplant
Also available IV form (used more for transplant) toxicity is decreasing seizure threshold |
|
|
**Melphalan (Alkeran)
|
Used for the treatment of multiple myeloma
8 mg/m2 PO daily day 1-4 repeat every 28 days All three of these medications come as 2 mg tablets (watch dispensing by brand name) |
|
|
Temozolomide (Temodar)
|
Used for treatment of brain tumors
150 mg/m2 PO daily days 1-5 a cycle repeat cycle every 28 days |
|
|
Anthracyclines
|
Doxorubicin (Adriamycin®, hydroxy-daunorubicin)
Daunorubicin Idarubicin Epirubicin Mitoxantrone |
|
|
MOA of Anthracyclines
|
Inhibition of topoisomerase II
Intercalation between DNA base pairs, interfering with DNA synthesis Formation of free radicals that damage DNA and cell membranes non cell cycle specific |
|
|
Toxicities Anthracyclines
|
Myelosuppression
Cardiotoxicity Extravasation injury Treat with Wydase and cold Nausea and vomiting Mucositis red/orange urine discoloration **Mitoxantrone has less free radical formation; therefore, less risk of cardiotoxicity, extravasation injury, N/V, mucositis |
|
|
Cardiotoxicity Anthracyclines
|
Acute
arrhythmias within 24 hours of administration Related more to peak concentrations Chronic cardiomyopathy secondary to free radical formation cumulative doses > 550 mg/m2 |
|
|
Cardiotoxicity prevention and Dexrazoxane
|
Cardioprotectant
Disrupts iron-anthracycline complex Prevents free radical formation without interfering with cytotoxic activity Used in leukemia with patients who have underlying heart dysfunction |
|
|
Liposomal doxorubicin (Doxil®)
and decr risk of cardiotoxicity |
Liposomal delivery system not as readily taken up by cardiac tissue decr risk of cardiotoxicity
Used in breast, ovarian cancer |
|
|
Mitoxantrone
|
Similar ring structure to anthracyclines
Similar mechanism of action, with decreased tendency for free radical formation Decreased cardiotoxicity and extravasation Decreased nausea and vomiting Blue-green urine discoloration and tears and sweat etc.. |
|
|
Bleomycin
|
Anthracycline
Used in testicular cancer, Hodgkin’s Disease Test dose needed only for Hodgkin’s disease Watch for pulmonary toxicity and N/V |
|
|
Mitomycin C
|
Anthracycline
used in gastrointestinal tumors used intravesicularly in bladder cancer Sent to OR for shake and bake |
|
|
Antimetabolites
|
Cell cycle specific- creation/formation of DNA base pairs
Antifolates Purine analogs Pyrimidine antagonists |
|
|
Antifolates
|
Methotrexate* (MTX)
Pemetrexed (Alimta) |
|
|
Purine Analogs
|
Mercaptopurine* (6-MP)
Thioguanine* (6-TG) Fludarabine Cladribine |
|
|
Pyrimidine Antagonists
|
Cytarabine (Ara-C)
Gemcitabine (Gemzar®) Fluorouracil (5-FU) Capecitabine* (Xeloda®) |
|
|
Methotrexate
|
Taken up intracellularly by cancer & healthy cells
Inhibits dihydrofolate reductase tetrahydrofolate purine & thymidylate Lack of purines & thymidylate prevents DNA synthesis Leucovorin rescue Reduced folate that bypass MTX inhibition of tetrahydrofolate synthesis Uptake healthy cells > cancer cells then give leucovorin to "rescue" normal cells. Given after tx with methotrexate |
|
|
Toxicities of Methotrexate
|
Myelosuppression and mucositis
Nephrotoxicity (crystallization of MTX) Avoid nephrotoxic meds (NSAIDs, sulfa) Neurotoxicity (with IT therapy)- crystalizes in tubules--avoid nsaids and sulfadrugs Photosensitivity, eye discomfort Pneumonitis Hepatotoxicity |
|
|
Preventing toxicitie with methotrexate
|
prevent renal damage by alkalinizing the urine with sodium bicarbonate solutions
avoid drugs that can interfere with excretion of methotrexate: Bactrim, NSAIDS, etc. leucovorin rescue with high doses (yellow card) can accumulate in fluid and leach out over time causing serious toxicity – ensure patient has no fluid collections (ascitis, pleural effusions, etc.) Make sure CXR is obtained prior to dose |
|
|
Leucovorin Rescue
|
needed when administering high-doses of methotrexate > 100-500 mg/m2
directly converted into tetrahydrofolate without the need for dihydrofolate reductase begin 24 hours after methotrexate given should be given until methotrexate level is < 0.05 micromolar (5 x 10-8M) Refer to yellow card May give carboxypeptidase (from NCI) Needs IRB approval prior to dose |
|
|
Pemetrexed (Alimta)
|
inhibits multiple enzymes involved in folate metabolism and DNA synthesis
used for malignant pleural mesothelioma, non-small cell lung cancer cutaneous reactions – prevent with dexamethasone 4 mg bid day -1, 0, +1 give folic acid 350-1000 mcg daily and vitamin B12 1000 mcg IM q 9 weeks starting week before initiation and for 21 days after therapy to prevent hematologic and gastrointestinal toxicity |
|
|
Cytarabine (Ara-C)
know dose ranges |
Arabinose analog of cytosine
Phosphorylated to active component within cancer cells Inhibits DNA polymerase |
|
|
Toxicities with Cytarabine
know dose ranges |
Myelosuppression (100 mg/M2/day)
Alopecia Gastrointestinal Rash—plantar-palmer syndrome High dose toxicities (3 g/M2 q12h) nausea CNS toxicity chemical conjunctivitis, acral erythema |
|
|
Gemcitabine (Gemzar®)
|
MOA & structure similar to cytarabine
Intermittent dosing more effective than continuous dosing Effective for solid tumors Pancreatic cancer NSCLC Achieves intracellular concentrations 20x greater than cytarabine |
|
|
Toxicity with Gemcitabine
|
Myelosuppression
Generalized rashes Fever and flu-like symptoms Peripheral edema Nausea and vomiting-mild NOT Neurotoxic |
|
|
Other Pyrimidine antagonists
|
Clofarabine (clolar)
Nelarabine (arranon) |
|
|
Clofarabine
|
Relapsed pediatric ALL
Peds 52 mg/m2 IV daily x 5 days Adults 30-40 mg/m2 IV daily x 5 days AE-skin toxicity-rash to desquamation |
|
|
Nelarabine
|
Tcell ALL or Tcell lymphoblastic lymphoma
Peds 650 mg/m2 IV daily for 5 days Adults 1500 mg/m2 IV Day 1,3,5 AE-neurotoxicity |
|
|
MOA of Fluoruracil
|
fluorinated analog of uracil
prodrug that is metabolized to FdUMP in order to be active FdUMP binds to thymidylate synthase (TS) prevents conversion of uracil (RNA) to thymidine (DNA) stabilizes TS & FdUMP in the presence of leucovorin (given with leucovorin to treat colon cancer) |
|
|
Toxicity of Fluorouracil
|
Myelosuppression (bolus)
Bloody diarrhea (CI) Mucositis (CI) Dermatologic Ocular Nausea and vomiting (mild) Cardiotoxicity (rare) you get a white line on your nails for each cycle of 5FU you get |
|
|
Capecitabine (Xeloda®)
|
Oral prodrug of fluorouracil
Metabolized to active component in tumor tissue Use in metastatic colorectal & breast cancer Take BID with food (↓ N/V) Diarrhea, palmar-plantar rash |
|
|
Purine Analogs
|
Inhibit de novo purine synthesis
Mercaptopurine (6-MP) Metabolized by xanthine oxidase ↓ dose x 75% if used with allopurinol Thioguanine (6-TG) No dose reduction required with allopurinol Fludarabine & cladribine Immunosuppressive → risk of opportunistic infections |
|
|
Mitotic inhibitors
|
Vinca alkaloids
Vincristine (Oncovin®) Vinblastine (Velban®) Vinorelbine (Navelbine®) Taxanes Paclitaxel (Taxol®) Docetaxel (Taxotere®) |
|
|
MOA of mitotic inhibitors
|
“Spindle poisons” which bind to tubulin
Vinca alkaloids Inhibit microtubule assembly Interfere with formation of mitotic spindle Cells accumulate in mitosis Taxanes Promote microtubule assembly Interfere with microtubule disassembly |
|
|
Mitotic Inhibitor Toxicities
|
Vincristine
Neurotoxicity Constipation Vesicant Extravasation SIADH Do not give Intrathecally Vinblastine/Vinorelbine Myelosuppression Vesicant Extravasation |
|
|
Vinorelbine (Navelbine)
|
semi-synthetic vinca alkaloid
used for lung, breast, ovarian, lymphoma toxicities myelosuppression neuropathy nausea and vomiting extravasation alopecia |
|
|
Toxicities with the Taxanes
|
Myelosuppression
Mucositis Peripheral neuropathy (cumulative) Alopecia Hypersensitivity reactions* Nausea and vomiting (rare) *** Premedicate with dexamethasone, H1- & H2-antagonist |
|
|
toxicities Paclitaxel
|
Myalgia
Bradycardia Cremaphor EL |
|
|
toxicities with Docetaxel
|
Fluid retention
Palmar-plantar rash Polysorbate-80 |
|
|
Ixabepilone (ix-a-BEP-i-lone) Ixempra® (ix-EM-pra)
|
Semi-synthetic analog of epothilone B
Binds directly to ß-tubulin on microtubules, leading to suppression of microtubule dynamics Some binding sites overlap with paclitaxel accounts for its activity in taxane resistant patients |
|
|
Ixabepilone: Adverse Events
|
Neurotoxicity about 65% overall in studies
Neutropenia incidence 65% but febrile neutropenia incidence only 3-4% Premeds: H1 blocker – diphenhydramine 50 mg H2 blocker – ranitidine 50 mg IV |
|
|
Epipodophyllotoxins
|
Etoposide (VP-16) & teniposide (VM-26)
Inhibit topoisomerase II Toxicities Myelosuppression Mucositis (BMT) Hypotension (diluent) Clinical uses VP16 – AML, NHL, BMT, solid tumors (IV or oral) VM26 – ALL, SCLC |
|
|
Camptothecins
|
Irinotecan & topotecan
Inhibit topoisomerase I Clinical uses Ovarian cancer Lung cancer CML, MDS Cervical, ovarian cancer Colorectal cancer |
|
|
toxicities of Camtothecins
|
Topotecan: myelosuppression
Ironotecan: Severe diarrhea (20%) Acute (≤ 24 hours) Facial flushing, abdominal cramping Treat with scopolamine or atropine Prevent with 5HT-antagonist & antihistamines Chronic (~11 days) Secretory → life threatening dehydration Treat with loperamide -iimmodium |
|
|
L-asparaginase
|
Degrades asparagine found in the serum
In lymphoid malignancies the lymphocytes are unable to produce asparagine due to a lack of or low levels of asparagine synthetase and rely on serum asparagine for its needs. Without the serum asparagine the cells are unable to grow and reproduce Used for ALL Adverse Events pancreatitis (check amylase) *decreased fibrinogen < 100mg% (clotting problems) if low give cryoprecipitate *hypersensitivity reactions, if so give Erwina asparaginase or peg-asparaginase (more expensive) Peg-asparaginase-larger molecule therefore given less frequent |
|
|
Hydroxyurea (Hydrea)
|
Used for CML
Causes myelosuppression Doses 50 mg/kg/d (aprx 500 mg PO BID & titrate to WBC effect) |
|
|
Bortezomib (Velcade)
|
Selective, reversible inhibitor of the proteasome
Proteasome: multi-enzyme complex in all cells; degrades proteins and regulates cell-cycle progression Adverse events: peripheral neuropathy, fatigue, malaise, weakness, GI effects, thrombocytopenia Used for Multiple Myeloma, NHL, ? leukemias |
|
|
All-trans retinoic Acid (Vesinoid)
|
Used with APL
Matures promyelocytes blasts inducing a CR May cause retinoic acid syndrome that needs to be treated with dexamethasone Dose: 45 mg/m2/d (round to nearest 10 mg) PO divided BID with food up to 90 days Give with cytarabine and daunorubicin Retinoic acid syndrome- fever, dyspnea, pleural effusion, peripheral edema, hypotension treat-dexamethasone 10 mg IV BID x 3 days |
|
|
arsenic trioxide (Trisenox)
|
used for APL
retinoic acid syndrome (differentiation syndrome) QTC prolongation |
|
|
thalidomide
|
for multiple myeloma (first for leprosy)
increase risk for thromboembolism- esp when given in combo w/ dexomethosone **use VTE prophylaxis** drowsiness peripheral neuropathies pts / prescribers / dispensers must enroll in STEPS |
|
|
Lenalidomide (Revlimid)
|
for MDS and MM
Myelosuppression |
|
|
Hypomethylating Agents
|
Cells need methyl groups to grow
Removes methyl groups leading to cancer cell death Azacitadine (Vidaza) Decitabine (Dacogen) |
|
|
Azacitadine (Vidaza)
|
hypometh agent
Used for MDS Given 75-150 mg/m2 SQ or IV daily x 7 days SQ route has local reaction |
|
|
Decitabine (Dacogen)
|
hypometh agent
Used for MDS 15 mg/m2 IV every 8 hours x 9 doses every 6 weeks 20 mg/m2 IV daily x 5 days every 4 weeks |
|
|
Histone Deacetylators (HDACs)
|
Cancer cells can have too much HDAC which allows the cell to grow unregulated (unable to die)
If inhibit HDAC, then allows the cell to develop normally and complete cell life Ultimate goal is cell death through normal cell regulation Histone: “spools” around which DNA wind Histones contain lysine-rich amino-terminal tails that are responsible for conformational change by DNA Histone deacetylases (HDACs) remove acetyl group to lysine tail, restores charge, increases attraction between histones and DNA → condensation of chromatin → represses transcription |
|
|
Vorinostat (Zolinza)
|
Some tumor cells produce excess amounts of histone deacetylase (HDAC), leading to a closed chromatin structure and prevention of DNA transcription
HDAC inhibitors have also been shown to: Cause cell cycle arrest Induce apoptosis Inhibit angiogenesis Clinical Use Cutaneous manifestations in patients with cutaneous T-cell lymphoma (CTCL) who have progressive, persistent or recurrent disease on or following two systemic therapies No dosing recommendations for hepatic or renal impairment Patients should drink at least 2 liters/day of fluid to prevent dehydration |
|
|
side effects Veronistat
|
Hematologic abnormalities
Anemia Thrombocytopenia Gastrointestinal symptoms Diarrhea, nausea Taste disorders May prolong QTc interval Serious but rare Pulmonary embolism Squamous cell carcinoma Anemia Laboratory abnormalities Increased serum creatinine Hyperglycemia Proteinuria |
|
|
mTOR inhibitor Temsirolimus (Torisel™)
|
MOA: Inhibition of mTOR blocks translation of mRNA and halts progression from G1 to S phase
Treatment of advanced renal cell carcinoma Dose 25 mg IV over 30-60 minutes once a week Premedicate with antihistamine (i.e. diphenhydramine) Hold for ANC < 1,000/mm3, platelet < 75,000/mm3, grade 3 AE’s Restart when toxicities resolve to grade 2 Reduce dose by 5 mg/week (minimum dose 15 mg) |
|
|
Temsirolimus: Adverse Events
|
Hypersensitivity reactions (9%)
Hyperglycemia / Hyperlipidemia -mTOR plays role in glucose and lipid metabolism Immunosuppression -Infections and impaired wound healing Bowel Perforation Fatal in 1 patient Renal Failure Interstitial lung disease (2%) |
|
|
Targeted Therapies
|
monoclonal antibodies
tyrosine kinase inhibitors |
|
|
Monoclonal Antibodies
|
antigens
radioisotopes EGFR VEGF |
|
|
tyrosine kinase inhibitors
|
bcr-abl
EGFR |
|
|
Monoclonal Antibody
(Mab) MOA |
Destroys tumor cells through a number of possible mechanisms, including activation of complement and antibody-dependent cell-mediated cytotoxicity
Useful as means of targeting cytotoxic radioisotopes, toxins, or drugs to tumors, enhancing their delivery to tumors while minimizing systemic exposure Animal (murine/equine), human or chimeric derived |
|
|
Monoclonal Ab naming
|
momab-radiolabeled
-tositumomab zumab-human -alemtuzumab ximab-chimeric with murine & human -cetuximab |
|
|
MAB Toxicities
|
Infusion-related toxicity (65-80%): SOB, temp, chills, nausea, asthenia, and HA
premedications—acetaminophen, diphenhydramine, hydrocortisone Hypotension (10%)-recommend holding anti-hypertensives |
|
|
1st Gen MAB
|
Rituximab (Rituxan)
Gemtuzumab ozoamicin (Mylortag) Alemtuzuman (Campath) |
|
|
Rituximab (Rituxan)
|
Anti-CD-20 antigen found on B lymphocytes
Used for B-cell non-Hodgkin’s lymphoma |
|
|
Gemtuzumab ozogamicin (Mylotarg)
|
Anti-CD-33 antigen linked to ozogamicin
Used for Acute melogenous leukemia (AML) Profound bone marrow suppression |
|
|
Alemtuzumab (Campath)
"liquid AIDS" |
Anti-CD-52 antigen found on B and T lymphocytes
Used for B-cell chronic lymphocytic leukemia Profound immunosuppression |
|
|
Radiolabeled MAB
|
ibritumomab (Zevalin)
tositumomab (Bexxar) |
|
|
ibritumomab (Zevalin)
|
antibody linked to radioactive isotope yttrium-90, directed against CD-20
given with rituximab used in follicular non-Hodgkin’s lymphoma |
|
|
tositumomab (Bexxar)
|
antibody linked to radioactive isotope iodine-131, directed against CD-20
used in follicular non-Hodgkin's lymphoma |
|
|
Tyrosine Kinase Inhibitors
|
external MAB
Internal small moel tyr kin inhib |
|
|
Tyrosine Kinase
|
Regulates cellular proliferation, differentiation, function, & survival
Receptor & non-receptor TKs FLT3, VEGF, ABL, c-KIT, etc. Activity tightly controlled in normal cells |
|
|
TK inhibitors MOA
|
Small molecule inhibition:
Blocks ATP binding to kinase domain Stops intracellular signaling pathways Cellular apoptosis Monoclonal antibodies: Target receptor TKs or the ligand Interrupt TK signaling Antibody-mediated cytotoxicity |
|
|
Small molecule inhibitors
|
Imatinib (Gleevec®)
Gefitinib (Iressa®) Erlotinib (Tarceva®) Sunitinib (Sutent®) Sorafenib (Nexavar®) |
|
|
Monoclonal Antibodies
|
Cetuximab (Erbitux®)
Trastuzumab (Herceptin®) Bevacizumab (Avastin®) |
|
|
Monoclonal Antibodies: breast CA
Trasruzumab - Herceptin |
binds to the extracellular domain of the human epidermal growth factor receptor 2 protein (HER-2) found on some breast cancers
used for metastatic breast cancer whose tumors overexpress the HER-2/neu protein can cause congestive heart failure |
|
|
Monoclonal Antibodies: colon cancer
|
bevacizumab (Avastin)
cetuximab (Erbitux) |
|
|
bevacizumab (Avastin)
|
antibody against vascular endothelial growth factor (VEGF)
used for metastatic colorectal cancer inhibits blood vessel formation (do not give within a month of surgery) causes hypertension |
|
|
cetuximab (Erbitux)
|
antibody against epidermal growth factor receptor (EGFR)
used for metastatic colorectal cancer causes acneform rash |
|
|
Panitumumab (Vectibix)
|
Patients with EGFR-expressing, metastatic colorectal carcinoma with disease progression on or following one or more regimens containing:
Fluoropyrimidine, Oxaliplatin, or Irinotecan 6 mg/kg IV every other week Premedications are necessary Toxicities: Pulmonary fibrosis dermatologic toxicity infusion reactions Hypomagnesemia N/V/constipation |
|
|
TK inhibitors Lung Cancer
|
erlotinib (Tarceva)
gefitinib (Iressa) |
|
|
erlotinib (Tarceva)
|
inhibits epidermal growth factor receptor (EGFR) tyrosine kinase
used as salvage treatment of non-small cell lung cancer causes acneiform rash, diarrhea, interstitial lung disease |
|
|
gefitinib (Iressa)
|
inhibits epidermal growth factor receptor (EGFR) tyrosine kinase
used for non-small cell lung cancer in patients who are benefiting or have benefited from gefitinib skin rash, ocular symptoms, pulmonary symptoms |
|
|
Toxicities with EGFR inhibitors
|
Skin rash (72%)
Diarrhea (35%) Nausea/vomiting Myelosuppression Pulmonary symptoms (SOB, cough, fever) with acute onset or worsening |
|
|
Tyrosine Kinase Inhibitors: CML
|
inhibits Bcr-Abl tyrosine kinase
-Bcr-Abl is the abnormal gene product that is caused by the Philadelphia chromosome in chronic myeloid leukemia (CML) -also inhibits tyrosine kinase for platelet derived growth factor (PDGF), stem cell factor (SCF) and c-kit |
|
|
toxicity with TKI's and CML
|
Musculoskeletal pain
Fluid retention QT prolongation Myelosuppression GI Bleeding Dyspnea Cardiac failure Diarrhea Headache Dizziness Constipation Pyrexia Fatigue Skin Rash Nausea/Vomiting Cough Anorexia Pain Neuropathy |
|
|
Imatinib (Gleevec)-CML
|
used to treat Philidelphia chromosome + CML and Kit-positive gastrointestinal stromal tumors (GIST)
Dose: 400 to 800 mg daily There are a lot of mutations that may be overcome except T315I--if they have this mutation they have to have a transplant |
|
|
Dasatinib (Sprycel)
|
Adults with chronic, accelerated, or myeloid or lymphoid blast phase chronic myeloid leukemia with resistance or intolerance to prior therapy including imatinib
Take antacid 2 hrs prior to or after dose Major drug interactions: With CYP3A4 inhibitor, decrease dose to 20-40 mg daily Consider increase in dose if given with CYP3A4 inducer |
|
|
Nilotinib (Tasigna)
|
Similar indication as dasatinib
No food 2 hours prior to or 1 hour after dose Major CYP3A4 interactions but no official recommendations |
|
|
Tyrosine Kinase Inhibitors: renal cell cancer
|
Sorafenib (Nexavar)
Sunitinib (Sutent) |
|
|
Sorafenib (Nexavar)
|
Advanced renal cell carcinoma in adults
inhibits RAF kinase Bioavail decr with high fat meal |
|
|
Sunitinib (Sutent)
|
Gastrointestinal stromal tumors (GIST) after disease progression or intolerance to imatinib
Advanced renal cell carcinoma in adults VEGFR an PDGFR inhibitornot affected by food |
|
|
Adverse Effects with Sorafenib and Sunitinib
|
Fatigue, diarrhea, nausea, vomiting, constipation, hypertension, rash, hand-foot syndrome, dyspnea, cough, anorexia, bleeding, myelosuppression
|
