CTX not in sketchy Flashcards
What are the indications for cyclophosphamide in cancer?
What about for ifosphamide?
Breast cancer
Non-Hodgkin’s lymphoma
Testicular cancer
Soft tissue carcinoma (sarcomas)
What drug is an analogue of cyclophosphamide?
Ifosfamide
What type of drug is temozolomide? (MoA?)
Alkylating agent
Monofunctional alkylating agent: spontaneous hydrolysis of DNA-active species and methylates DNA.
What is the indication for temozolomide?
Brain tumors (GBM)
What are the toxicities for temozolomide?
Myelosuppression
*Pneumocystic PNA
N/V, hair loss
What drug helps prevent hematuria (and hemorrhagic cystitis) w/ifosphamide administration? (and rarely w/cyclophosphamide)?
Mesna
Which of the platinum agents have the same indications?
Cisplatin + carboplatin
What are the indications for cisplatin + carboplatin?
What is the indication for oxaliplatin?
Testicular cancer (curative!) Lung, ovary, head/neck, bladder cancers
Colorectal cancer (doubles survival)
Which of the platinum agents can cause neuropathy?
(Cisplatin)
Oxaliplatin (dose-limiting)
Which of the platinum agents can cause myelosuppression?
(*cisplatin does NOT cause myelosuppression)
Carboplatin
Oxaliplatin
Which of the platinum agents can cause ototoxicity?
Cisplatin
Which of the platinum agents can cause nephrotoxicity?
How can it be prevented?
Cisplatin
Administer with hydration and mannitol diuresis (chloruresis)
Dose reduction for renal insufficiency
Describe the types of neuropathy that can seen w/oxaliplatin.
- Acute cold-induced neuropathy (begins immediately)
- Chronic sensory neuropathy (mild, rarely disabling and slowly resolves)
Which of the platinum cmpds can cause hypomagnesemia?
Cisplatin
Which of the platinum cmpds is a vein irritant?
Oxaliplatin
What are the indications for vincristine?
What are the indications for vinblastine?
Lymphoma
Hodgkin’s disease
Acute lymphoblastic leukemia
Lung & breast cancer
What are the indications for paclitaxel?
Ovarian cancer
Breast cancer
Gastroesophageal cancer
Non-small cell lung cancers
(OBG N)
Which of the vinca (plant) alkaloids are vesicants?
All (vincristine, vinblastine, taxanes)
What is the major reason to adjust dose for the vinca alkaloids?
Dose reduction in presence of jaundice (order bili)
What are some SE’s of paclitaxel besides neuropathy, myelosuppression, and being a vesicant?
How can you avoid an infusion rxn w/paclitaxel?
Stomatitis, arthralgias/myalgias.
Premedicate with steroids
Which drug categories are cross-resistant due to MDR?
The intercalating and non-intercalating topoisomerase II inhibitors and the tubulin inhibitors (vinca alkaloids)
What are the indications for etoposide?
Small cell lung cancer
Testicular cancer
Lymphoma
(small testicular lymphoma)
What specific type of cancer can etoposide cause?
What other minor SE’s does it cause (besides hair loss, myelosuppression)?
Leukemogenic
N/V
Are any of the platinum cmpds emetogenic? Which?
Cisplatin
Oxaliplatin causes N/V as well
When would you adjust your dose w/etoposide?
Dose reduce for hepatic or renal dysfunction
What are the indications for ironotecan?
GI tract (eg colon) cancers
What are the 2 types of diarrhea seen w/ironotecan?
How would you treat each?
Early cholinergic diarrhea treated with atropine
Late secretory diarrhea (treated w/imodium & hydration)
When would you adjust your dose w/ironotecan?
Dose reduction for jaundice (order bili)
Pts w/Gilbert’s syndrome should not be given what chemo drug?
Why?
Ironotecan
UGT1A1*28 (decreases glucuronidation and increases myelosuppression and diarrhea, mutation in 9% of Caucasian and African population)
What are the toxic SE’s for cyclophosphamide and ifosfamide besides myelosuppression and hematuria/hemorrhagic cystitic?
What other unique SE’s can ifosfamide have at high doses?
Both: N/V, hair loss
Ifosfamide: lethargy and confusion
Describe how AUC is related to carboplatin.
What is the equation for AUC calculation?
Linear relationship between GFR and carboplatin plasma clearance
Dose (mg)=AUC x (GFR + 25)
Which of the platinum drugs is easiest to administer?
Carboplatin.
What are the indications for doxorubicin?
Breast cancer Leukemia Sarcoma Hodgkin’s lymphoma Non-Hodgkin’s lymphoma
How would you specifically describe the pharmacologic category of the cardiotoxicity of doxorubicin?
Schedule-dependent cumulative
anti-tumor effect is schedule-independent
What other SE’s does doxorubicin cause besides myelosuppression, cardiotoxicity, hair loss, and stomatitis?
N/V
Vesicant
What lab values should you get w/doxorubicin?
Obtain EF 1st due to irreversible cardiotoxicity (ultrasound, etc.). Also get a bilirubin to avoid jaundice.
(Maximum life time dose: 400 mg/M^2)
How would you avoid the cardiotoxicity of doxorubicin?
When else would you reduce the dose?
Pretreatment with an iron chelator may be helpful: dexrazoxane
Dose reduction for jaundice
When is bleomycin indicated?
Testicular cancer
How would you specifically describe the pharmacologic category of the pulmonary adverse effects of bleomycin?
Cumulative
Avoid high inspired concentrations of oxygen:
When pts w/ h/o bleomycin administration are given high inspired O2 concentrations, there is a risk of pulmonary damage and death. If O2 is necessary, administer the lowest FiO2 to maintain oxygen saturation > 90 %.
When would you reduce the dose of bleomycin, besides in pulmonary toxicity?
Reduce dose in those w/renal insufficiency (excreted in urine)
What are the indications for prednisone?
In high doses for lymphoma and multiple myeloma (lymphoproliferative and myeloproliferative diseases).
What are the indications for dexamethasone? (2)
- Reduce cerebral edema and initial tx for spinal cord compression (less mineralocorticoid activity vs. prednisone).
- In combo w/ other agents (5HT3 inhibitors) to treat chemotherapy-related emesis
What is the ‘flare rxn’ w/leuprolife administration?
How could you avoid the flare reaction seen w/leuprolide acetate administration to treat prostate cancer?
Initial worsening of sx in pts w/ prostate cancer since T production initially increases before decreasing.
Therefore, the pt is treated with flutamide or bicalutamide for 2-4 weeks before institution of leuprolide tx (depot injections). The flutamide or bicalutamide are then discontinued.
(lutamides are androgen-receptor antagonists)
Recall: what can leuprolide treat in men? (1)
Recall it’s MoA
Side effects of leuprolide acetate?
Prostate cancer
Sustained activation of GnRH receptor inhibits release of gonadotropins
Weakness, decreased libido, ED, loss of muscle mass, gynecomastia, change in body fat distribution
What cancers is MTX effective against?
Lymphoma, leukemia
Brain tumors
Breast cancer
RA; psoriasis
How do you need to alter MTX administration in order to treat brain tumors effectively?
High dose required to penetrate CNS
When would you reduce the dose of MTX?
When else is MTX contraindicated? (why?)
Renal insufficiency
Volume of distribution is total body water: contraindicated in ascites & pleural effusions; probenicid
How do ASA, PCN, and sulfonamides interfere w/MTX administration, specifically?
Enhanced toxicity if given with drugs that displace MTX from albumin binding site and/or decrease excretion of drug in urine (eg ASA, sulfonamides, PCN)
How can MTX be administered?
*Intrathecal, IM, PO
What are the indications for 5-FU?
GI, breast, head, and neck cancer
Given concomitantly w/radiation as “radiation sensitizer”
What is a rare SE’s a/w 5-FU that was not covered in sketchy?
Rare: coronary artery vasospasm and cerebellar toxicity
What drug is effected by leucovorin (besides MTX), and how?
Leucovorin enhances the cytotoxicity of 5-FU, as well as SE’s.
What genetic tested in required when giving 5-FU?
Dihydropyrimidine DH (DPD) deficiency Dihydropyrimidine is 5-FU's hepatic metabolite will produce severe toxicity if 5-FU administered (common).
What is the specific indication for hydroxyurea?
Emergently decreases high WBC count in pts with AML.
High white counts in myeloid leukemias can produce leukostasis in capillaries and lead to organ damage and death
What is pemetrexed’s MoA? (What drug is this similar to?)
What are the toxicities a/w pemetrexed?
Antifol; polyglutamated.
Cell cycle specific (S phase)
Inhibits thymidylate synthase. (similar to 5-FU)
Myelosuppression (dose-limiting. Pretreatment with vitamin B-12 and oral folic acid decreases the extent of myelosuppression)
Hand-foot syndrome
Rash, stomatitis, diarrhea (similar to 5-FU w/o the rare cardiac vasospasms and cerebellar toxicity)
When is pemetrexed indicated?
Lung cancer
Mesothelioma
What type of cancer does cytosine arabinoside AKA cytarabine treat?
AML
What are the toxicities a/w cytarabine besdies myelosuppression?
What additional toxicities are a/w the high dose form?
N/V, hair loss, stomatitis
Hepatic toxicity
High dose: cerebellar toxicity, conjunctivitis, myelosuppression
Besides doxorubicin, what other anti-cancer drug we went over has schedule-dependent toxicity?
Cytarabine aka cytosine arabinoside
What is the specific dosing regimen used for cytarabine when treating AML (and what is the other drug used in this regimen)?
3 + 7 regimen: 3 days of doxorubicin or daunorubicin and 7 days of continuous infusion of cytarabine
What are the indications for gemcitabine (fluorinated analogue of cytarabine)?
Pancreas and lung cancers
What is the name of the pro-drug of 5-FU?
Why would it be given instead of 5-FU?
Capecitabine
Can be given PO
What toxicities are a/w capecitabine (pro-drug of 5-FU)?
Rash, diarrhea, stomatitis, hand-foot syndrome, some myelosuppression
What is 6-mercaptopurine used to treat?
Childhood leukemia
Why would you use the analogue of 6-MP? (name the analogue as well)
6-thioguanine can be used at full dose when the patient is also receiving allopurinol because 6-thioguanine undergoes deamination that does not involve the enzyme xanthine oxidase
What are the SE’s of imatinib besides edema?
Nausea, muscle cramps, abdominal pain, rash, diarrhea, anemia, neutropenia and thrombocytopenia.
What “tinib” agents are metabolized by CYP3A4?
Imatinib mesylate
Erlotinib
W/what agent must you monitor thyroid hormone levels?
Imatinib
Monitor TSH levels: increases the clearance of TH in hypothyroid pts taking thyroid replacement therapy.
How is mutational analysis a/w erlotinib tx?
Pts w/EGFR-activating mutations are more sensitive to erlotinib (perform mutational analysis prior). If the tumor has an “activating mutation” of EGFR, erlotinib and NOT ctx is the treatment of choice for metastatic adenocarcinoma of lung.
What are the toxicities of erlotinib besides rash and diarrhea?
Anorexia, fatigue.
What other drug is closely related to sorafenib and sunitinib?
Pazopanib
What do sorafenib, sunitinib, and pazopanib all treat?
RCC
Besides RCC, what else can sorafenib treat?
Unresectable hepatocellular cancer
Besides RCC, what else can sunitinib treat?
Pancreatic neuroendocrine cancer
GI stromal tumor
What are the side effects of all VEGF-blockers (bevacizumab, sorafenib, sunitinib, and pazopanib), besides increased risk of hemorrhage, clotting, and colon perforation?
Hypertension, proteinuria, reversible posterior leukoencephalopathy syndrome (**PRES), infusion reactions.
Sorafenib, sunitinib, and pazpanib: also hand-foot syndrome & CHF (uncommon).
What is the name of the mutation in that must be seen to use vemurafenib to treat this type of melanoma?
V600E BRAF mutation
think about the name V600Emu(tation)RAFenib
What are the adverse effects of cetuximab besides infusion reactions and rash?
Diarrhea, hypomagnesemia
What cancers can cetuximab treat?
Lung cancer
Colorectal cancer
(Head & neck cancers receiving radiation tx)
Why should you do mutational analysis with cetuximab? (explain, including which of its indications)
K-RAS and N-RAS are better predictors to tx response than EGFR (they are downstream signalers) in colorectal cancer. Perform mutational analysis 1st to make sure they’re wildtype. If mutated: no response to cetuximab.
What are the indications for bevacizuab?
Lung cancer and metastatic colorectal cancer
must combine w/chemo
What cancer can trastuzumab be used to treat besides breast?
Gastric
What are some adverse effects of trastuzumab besides cardiotoxicity and infusion rxns?
Fever, nausea, vomiting, diarrhea, cough, headache, SOB, back pain, rash and muscle pain.
Allergic reactions.
Pts also receiving what medication have a higher risk of cardiac toxicity when taking trastuzumab?
Anthracycline
What must be monitored when giving trastuzumab?
EF
What is the MoA and indication for crizotinib?
Binds to anaplastic lymphoma kinase (ALK)
TOC for metastatic adenocarcinoma of lung if pt has ALK rearrangement.
What is the adverse effect a/w crizotinib?
Interstitial lung disease
What is the MoA for L-asparaginase?
Also, what is it’s indication?
Depletes asparagine pools rapidly. Leukemia cells lack asparagine synthetase and cannot synthesize asparagine. Cellular effects due to decrease in protein synthesis.
ALL
What are the adverse effects a/w L-asparaginase?
Allergic rxns; elevated liver enzymes; clotting (decreased AT3), pancreatitis; elevated glucose.
What is another name for all-trans retinoic acid (ATRA)?
Tretinoin
What is the MoA for ATRA?
What is its indication?
Induces terminal differentiation of leukemic cells
Acute promyelocytic leukemia (PML, or APL) (combined w/ctx)
What adverse effects are a/w ATRA?
Mucocutaneous toxicity
Retinoic acid syndrome: fever, weight gain, lung infiltrates and pleural or pericardial effusions
What is the MoA for arsenic trioxide?
What is its indication?
Allows myeloid differentiation to continue and apoptosis to occur
TOC for relapsed PML
What adverse effects are a/w arsenic trioxide?
Fatigue, weight gain, retinoic acid syndrome, QT prolongation
List the chemocurable cancers.
Hodgkin’s disease Diffuse Large B-Cell Lymphoma Childhood leukemia Metastatic testicular cancer Burkitt’s lyphoma Choriocarcinoma (female)
Which chemo agent can also be given concomitantly w/radiation as “radiation sensitizer”?
5-FU
What are the adverse effects of tamoxifen?
Hot flashes
Increased risk of thromboembolic events
Increased risk of endometrial cancer
What are the adverse effects of aromatase inhibitors?
Let Ana’s ex inhibit Aram
Arthralgias, bone pain, bone loss, osteoporosis, hot flashes
Review some adverse effects of glucocorticoids.
Weight gain, hypertension, edema, carbohydrate intolerance, suppression of pituitary-adrenal axis, weakness, euphoria, increased appetite
List the drugs that are cross resistant if MDR is the primary mechanism of resistance.
Vincristine (tubulin inhibitor)
Vinblastine (tubulin inhibitor)
Etoposide (Topo II inhibitor)
Doxorubicin (Topo II inhibitor)
Daunorubicin/Daunomycin (Topo II inhibitor)
Dactinomycin/Actinomycin D (Topo II inhibitor)
Which plant alkaloid is not a “spindle poison”?
Etoposide
Which drugs require a dose reduction in the presence of jaundice?
Vincristine Vinblastine Paclitaxel Doxorubicin Etoposide Ironotecan Cytarabine
Which drugs require a dose reduction in the presence of renal insufficiency?
Cisplatin
Bleomycin
Etoposide
Methotrexate
What other drug can be administered intrathecally besides MTX?
Cytarabine (aka cytosine arabinoside)
Why is alkalinization of the urine important in the implementation of the high dose
methotrexate with rescue strategy?
MTX solubility increases in high pH. Alkalinize to promote excretion.
Polyglutamation of methotrexate decreases the ability of leucovorin to rescue any cell
from the cytotoxicity of methotrexate. Why?
If cells have poly-glutamated MTX, leucovorin probably will not rescue. Bone marrow cells and gastrointestinal epithelial cells do not form polyglutamates. Therefore, bone marrow and GI epithelium is rescued.
