Chemo drugs Flashcards
• Antimetabolites
What toxicities are associated with methotrexate other than myelosuppression?
Macrovesicular fatty changes in the liver (hepatotoxicity), mucositis (e.g., mouth ulcers), pulmonary fibrosis, teratogenicity
What cancers are commonly treated with cytarabine (arabinofuranosyl cytidine)?
Leukemias (AML) and lymphomas
What are the clinical uses for 5-fluorouracil (5-FU)?
Colon cancer, pancreatic cancer, basal cell carcinoma (topical)
All the antimetabolites interfere with which phase of DNA synthesis?
S phase
Starting with DHF, go through the steps of the folate cycle, noting where the drugs methotrexate (MTX) and 5-fluorouracil (5-FU) act.
DHF to THF (via DHF reductase, blocked by MTX) to CH2-THF to DHF (converting dUMP to dTMP via thymidylate synthase, blocked by 5-FU)
An old man is given cladribine for a disease. What is its mechanism of action?
Can inhibit DNA polymerase and disrupt DNA double strands (he likely has hairy cell leukemia, and cladribine is a purine analog)
In a patient with TRAP-positive bone marrow and a dry tap on aspiration, what side effects does the chemotherapy drug of choice cause?
Myelosuppression, nephrotoxicity, neurotoxicity (hairy cell leukemia is treated with cladribine)
What drug, used as an antineoplastic agent, is a folic acid analog that works by inhibiting dihydrofolate reductase?
Methotrexate (inhibiting dihydrofolate reductase results in less deoxythymidine monophosphate needed for DNA and protein synthesis)
Name four cancers that methotrexate can be used to treat.
Leukemias (ALL), lymphomas, choriocarcinomas, and sarcomas
Name nonneoplastic conditions for which methotrexate can be used.
Ectopic pregnancy, medical abortion (with misoprostol), rheumatoid arthritis, psoriasis, IBD, vasculitis.
How does 5-fluorouracil (5-FU), a pyrimidine analog, interact with folic acid?
It is converted to 5F-dUMP, which covalently binds folic acid, forming a complex that inhibits thymidylate synthase
What enzyme is inhibited by the 5F-dUMP/folic acid complex?
Thymidylate synthase, which is needed to form deoxythymidine monophosphate for DNA and protein synthesis
A patient is given an excessive dose of 5-fluorouracil. Can leucovorin be administered to the patient to reduce toxicity?
No, as myelosuppression in this case is not reversible with leucovorin (it is with methotrexate toxicity)
What is the mechanism by which azathioprine, 6-mercaptopurine (6-MP), and 6-thioguanine (6-TG) exert an antineoplastic effect?
These are purine (thiol) analogs, which inhibit de novo purine synthesis (activated by HGPRT)
Azathioprine, 6-mercaptopurine, and 6-thioguanine are used in the prevention/treatment of what conditions?
Preventing organ rejection, rheumatoid arthritis, IBD, SLE, weaning off steroids for a condition, steroid-refractory conditions
Azathioprine, 6-mercaptopurine, and 6-thioguanine can be used to help wean patients off what other class of drugs?
steroids
How does cytarabine (arabinofuranosyl cytidine) exert its antineoplastic effect?
It is a pyrimidine analog that inhibits DNA polymerase (needed in S phase)
What are three adverse effects of cytarabine (arabinofuranosyl cytidine)?
Leukopenia, thrombocytopenia, and megaloblastic anemia (Cytarabine causes pancytopenia)
What agent is administered to reverse myelosuppression associated with methotrexate (MTX) use?
Leucovorin (rescue’s bone marrow)
What are three neoplasms in which dactinomycin is commonly used?
Ewing sarcoma, Wilms tumor, and rhabdomyosarcoma (in childhood tumors, actinomycin D because children act out)
Which of the antitumor antibiotics has the least myelosuppression as an adverse effect?
Bleomycin (myelosuppression is a common adverse effect of all other antitumor antibiotics)
What common mechanism is seen in the antineoplastic drugs bleomycin, daunorubicin, and doxorubicin?
These drugs generate free radicals, which can cause DNA strand breaks and halt cell replication
Which malignancies are treated commonly with doxorubicin or daunorubicin?
Solid tumors, leukemias, lymphomas
Name two neoplasms commonly treated with bleomycin.
Testicular cancer and Hodgkin lymphoma
A patient develops alopecia. What two chemotherapy drugs can cause this side effect?
Doxorubicin and daunorubicin
Name three antineoplastic drugs that function by intercalating into DNA strands.
Dactinomycin (actinomycin D), daunorubicin, and doxorubicin
A man on chemotherapy develops new symptoms of heart failure. What antineoplastic drug was likely a part of his regimen?
Doxorubicin or daunorubicin can cause dilated cardiomyopathy; patients may also develop alopecia, tissue toxicity on extravasation
A patient is started on chemotherapy that intercalates in DNA. What can you give to prevent cardiotoxicity from this drug?
Dexrazoxane (iron-chelating agent)
A patient with Hodgkin lymphoma complains of shortness of breath and dark skin discoloration. Which treatment was he likely given?
Bleomycin (causes pulmonary fibrosis and skin changes—other side effects are mucositis and myelosuppression)
A patient develops a dilated cardiomyopathy years after undergoing chemotherapy for breast cancer. What drug was likely part of her regimen?
Doxorubicin or daunorubicin (known to have cardiotoxic effects)
(also traztuzumab)
A patient with testicular cancer is given chemotherapy that generates free radicals. What side effects should he be worried of?
Pulmonary fibrosis, skin hyperpigmentation, and mouth ulcers (bleomycin is used to treat testicular cancer)
Which alkylating agent(s) require(s) activation by the liver and might not be effective in a patient with liver failure?
Cyclophosphamide and ifosfamide cause DNA cross-links at guanine N-7—both require bioactivation by the liver
Which alkylating agents are able to penetrate the blood-brain barrier to access the central nervous system? Do they require bioactivation?
Nitrosoureas, including carmustine, lomustine, semustine, and streptozotocin; yes, they require bioactivation
Which alkylating agent would you choose in a patient about to undergo hematopoietic stem cell transplantation?
Busulfan, which will ablate the host’s bone marrow before transplantation (also used in the treatment of chronic myelogenous leukemia)
What toxicities are seen in busulfan?
Severe myelosuppression (in almost all cases), pulmonary fibrosis, skin hyperpigmentation
A man with non-Hodgkin lymphoma develops hemorrhagic cystitis. What two alkylating agents can cause this side effect?
Cyclophosphamide and ifosfamide (myelosuppression is another side effect)
A patient on chemotherapy for breast cancer has hematuria. This could have been avoided by using what medication?
Mesna, its thiol group binds toxic metabolites; this patient has hemorrhagic cystitis from cyclophosphamide use
Which alkylating agents are used especially in treating central nervous system neoplasms?
Nitrosoureas cross the blood-brain barrier and are used for brain tumors (e.g., glioblastoma multiforme)
What is the major site effect of the nitrosourea chemotherapeutic agents?
CNS toxicity (convulsions, dizziness, ataxia)
A patient takes an antineoplastic drug that binds to β-tubulin during M phase, blocking microtubule formation. Which drug(s) might this be?
Vincristine or vinblastine
What neoplasms are commonly treated with a vinca alkaloid (vincristine or vinblastine)?
Solid tumors, leukemias, Hodgkin lymphoma (vinblastine), non-Hodgkin lymphoma (vincristine)
Vincristine Side effects?
Neurotoxicity, including areflexia, peripheral neuritis, and paralytic ileus
Vinblastine side effects?
Bone marrow suppression (vinblastine blasts bone marrow)
What antineoplastic drug functions by hyperstabilizing the mitotic spindle so that tumor cells are unable to complete anaphase?
Paclitaxel or other taxols (it is taxing to stay polymerized [the microtubule stays polymerized])
Which neoplasms are commonly treated using taxols?
Ovarian and Breast Ca
What are signs of toxicity with paclitaxel and other taxols?
Myelosuppression, alopecia, hypersensitivity
What are the clinical uses of cisplatin and carboplatin? What is the mechanism of action?
Testicular, bladder, ovary, lung carcinomas; they cross-link DNA
Cisplatin and Carboplatin Side effects?
Nephrotoxicity and ototoxicity (acoustic nerve damage)
A patient with testicular cancer is prescribed a DNA cross-linker. What drug can be coadministered to reduce toxicity?
Amifostine (a free radical scavenger) and chloride (saline) diuresis, both of which prevent cisplatin-induced nephrotoxicity
You give your cancer patient a drug that inhibits topoisomerase II. What are three of its toxicities?
Toxicities include myelosuppression, GI irritation, and alopecia (this is etoposide or teniposide)
What are the clinical uses for etoposide and teniposide? What is the mechanism of action?
Solid tumors (e.g., testicular and small cell lung cancer), leukemias, lymphomas; etoposide blocks topoisomerase II, causing DNA degradation
What is the mechanism of action of irinotecan and topotecan?
Both irinotecan and topotecan inhibit topoisomerase I and prevent DNA unwinding and replication
What toxicities are associated with irinotecan and topotecan use?
Severe myelosuppression and diarrhea
Which drug inhibits ribonucleotide reductase, acting during the S phase to decrease DNA synthesis?
Hydroxyurea (blocks DNA Synthesis and is S-phase specific)
What are the three clinical uses for hydroxyurea?
Melanoma, chronic myelogenous leukemia, and sickle cell disease (hydroxyurea increases concentration of hemoglobin F)
A boy with sickle cell anemia was recently prescribed hydroxyurea. How does it help him? What are two major toxicities of this medication?
Hydroxyurea increases concentration of hemoglobin F; bone marrow suppression and gastrointestinal upset
A patient with colorectal cancer on monoclonal antibody chemotherapy has scarily brisk bleeding from a wound. What might be the explanation?
He is likely on bevacizumab, which can cause hemorrhages, impaired wound healing, and blood clot formation as side effects
A woman develops a non-small cell lung cancer. What is a side effect of a tyrosine kinase inhibitor that can potentially help her?
Rash (erlotinib is often used for non-small cell lung cancer)
What is the mechanism of action of imatinib?
It inhibits the tyrosine kinase formed by the BCR-ABL translocation found in CML and by c-kit found in GI stromal tumors
A woman has morning stiffness that improves as the day goes on. She is prescribed a CD20 inhibitor. What side effect do you monitor for?
Progressive multifocal leukoencephalopathy (this is rituximab, a monoclonal antibody against CD20, which is found on most B-cell neoplasms)
What is the clinical use of vemurafenib? What is its mechanism of action?
Metastatic melanoma; it is a small molecule inhibitor of BRAF oncogene–positive melanoma
What are the toxicities of cisplatin/carboplatin?
Nephrotoxicity, acoustic nerve damage
