Chemotherapy

Front 1

Mechanism of chemotherapeutic action of alkylating agents?

Back 1

creates a reactive electrophillic intermediate (specifically carbonium or ethyleneimonium ion intermediate) that forms covalent linkages by alkylating nucleophilic moities present in DNA
-crosslinks guanine residues together

Front 2

Toxicity of alkylating agents?

Back 2

1.) bone marrow toxicity (neutropenia, anemia, thrombocytopenia)
2.) mucosal toxicity (oral mucosal ulceration, intestinal denudation)
3.) nausea anf vomiting
4.) toxic effects on reproductive systems (female amenorrhea and male sterility)
5.) increased leukemia risk

Front 3

Category/use of mechlorethamine?

Back 3

Alkylating agent (nitrogen mustard) used to treat Hodgkin's disease (in MOPP combo) and cutaneous T cell lymphoma

Front 4

Toxicity of mechlorethamine?

Back 4

-severe nausea and vomiting
-myelosupression (leukopenia and thrombocytopenia)

Front 5

Category/use of cyclophosphamide?

Back 5

Alkylating agent (nitrogen mustard) used to treat a broad clinical spectrum
-ALL, CLL, Non-Hodgkin's Lympoma
-Breast, lung, and ovarian cancers

Front 6

Category/use of ifosfamide?

Back 6

Alkylating agent (nitrogen mustard) used to treat sarcoma and testicular cancers

Front 7

Toxicity of cyclophosphamide?

Back 7

-nausea, vomiting
-myelosuppression
-hemorrhagic cystitis (local irritation in the bladder due to toxic drug metabolite in the urine)

Front 8

Toxicity of ifosfamide?

Back 8

-nausea, vomiting
-myelosuppression
-hemorrhagic cystitis (local irritation in the bladder due to toxic drug metabolite in the urine)

Front 9

Category/use of carmustine?

Back 9

Alkylating agent (nitrosourea) used to treat brain tumors (because its lipophillic properties allow it to easily cross the BBB)

Front 10

Category/use of lomustine?

Back 10

Alkylating agent (nitrosourea) used to treat brain tumors (because its lipophillic properties allow it to easily cross the BBB)

Front 11

Category/use of streptozocin?

Back 11

Alkylating agent (nitrosourea) used to treat pancreatic islet cell carcinomas and carcinoid tumors

Front 12

Toxicity of carmustine?

Back 12

-profound myelosupression
-severe nausea and vomiting
-renal toxicity
-pulmonary fibrosis

Front 13

Toxicity of lomustine?

Back 13

-profound myelosupression
-severe nausea and vomiting
-renal toxicity
-pulmonary fibrosis

Front 14

Toxicity of streptozocin?

Back 14

-profound myelosupression
-severe nausea and vomiting
-renal toxicity
-pulmonary fibrosis

Front 15

Category/use of dacarbazine?

Back 15

Alkylating agent (triazene) that makes up part of the ABVD combination regimen for treating Hodgkin's Disease and also treats malignant melanoma.
-prodrug that must be activated by cytochromes in liver
-given via IV

Front 16

Method of administration of dacarbazine?

Back 16

given via IV

Front 17

Category/use of temozolomide?

Back 17

Alkylating agent (triazine) that treats malignant gliomas (it is the standard agent given in combination with radiation therapy)

Front 18

Method of administration of temozolomide?

Back 18

given orally (excellent bioavailability)

Front 19

Toxicity of temozolomide?

Back 19

-nausea and vomiting
-myelosupression (neutropenia and thrombocytopenia)
-flu-like symptoms (fever, fatigue)

Front 20

Category/use of cisplatin?

Back 20

Alkylating agent (platinum analog) that treats testicular, ovarian, cervical, and bladder cancers
-can also treat head and neck cancers and lung carcinomas
-often used in combination regimens

Front 21

Mechanism of action of platinum analogs (cisplatin, carboplatin, and oxaliplatin)?

Back 21

Alkylating agents: covalently bind to nucliophilic sits on DNA after reacting with water to form positively charged hydrated intermediates that can react with guanine and form interstrand and intrastrand crosslinks

Front 22

Category/use of carboplatin?

Back 22

Alkylating agent (platinum analog) that is used to treat ovarian cancer

Front 23

Category/use of oxaliplatin?

Back 23

Alkylating agent (platinum analog) that is used in combination with 5-flurouracil to treat gastric and colorectal cancer

Front 24

Toxicity of cisplatin?

Back 24

-nephrotoxic (causes renal tubular damage and necrosis)
-ototoxic (with hearing loss)
-severe nausea and vomiting
-myelosuppression (mild to moderate)
-peripheral sensory and motor neuropathy

Front 25

Toxicity of carboplatin?

Back 25

myelosuppression (thrombocytopenia)

Front 26

Toxicity of oxaliplatin?

Back 26

-peripheral sensory neuropathy (cold-induced acute peripheral neuropathy- paresthesias)
-neutropenia

Front 27

Category/use of methotrexate?

Back 27

Antimetabolite (folate analog) used:
-for treating childhood ALL and choriocarcinoma
-in combination regimens for treating Burkitt's Lymphoma along with cancers of the breast, ovaries, head and neck, and bladder
-for treating meningeal leukemias and meningeal metastases from other cancers (administered intrathecally)
-for treating osteosarcoma (given at high doses)

Front 28

Toxicity of methotrexate?

Back 28

-bone marrow toxicity: myelosuppression and spontaneous hemorrhage
-GI toxicity: oral ulceration and stomatitis
-renal toxicity: methotrexate can crystallize in urine and cause renal damage
-hepatotoxicity: long-term use can lead to fibrosis or cirrhosis

Front 29

Route of administration of methotrexate?

Back 29

-usually given orally
-CAN BE GIVEN INTRATHECALLY (and must be to treat meningeal leukemia or meingeal metastases because cannot cross BBB)

Front 30

Mechanisms of resistance of methotrexate?

Back 30

-decreased uptake by neoplastic cells
-increased production of dihydrofolate reductase
-decreased affinity of dihydrofolate reductase for methotrexate

Front 31

What agent can be used to reduce the toxic effects of methotrexate?
How does this work?

Back 31

-Leucorvin, a fully activated form of folate, can reduce methotrexate's toxic effects
-leucorvin is taken up more readily by normal cells, which are consequently "rescued" from the detrimental effects of folate deficiency, while cancer cells can not effectively take up leucocorvin and are thus subject to methotrexate's cytotoxic effects

Front 32

Category/use of pemetrexed?

Back 32

Antimetabolite (folate analog) that is metabolized to active polyglutamate forms which inhibit THF-dependent enzymes, including dihydrofolate reductase and thymidylate synthase
-treats non-small cell lung cancer, mesothelioma, pancreatic cancer, and colon cancer

Front 33

Category/use of 5-fluorouracil?

Back 33

Antimetabolite (pyrimidine analog) prodrug that is enzymatically converted into active metabolites 5-FdUMP and 5-FdUTP
-5-FdUMP inhibits thymidylate synthetase and prevents synthesis of thyrmidine
-5-FdUTP is incorporated into RNA by RNA polymerase and interferes wiht RNA function
-used in combo therapy to treat breast, colorectal, gastric, pancreatic, and cervical cancers
-topical application used to treat basal cell carcinomas
-capecitabine (new oral form) used to treat metastatic breast cancer and colorectal cancer

Front 34

Category/use of capecitabine?

Back 34

Antimetabolite (pyrimidine analog) prodrug that is converted to 5'-dFdU
-new orally effective form of 5-fluorouracil used to treat metastatic breast cancer and colorectal cancer

Front 35

Toxicity of 5-fluorouracil?

Back 35

-anorexia and nausea
-mucosal ulceration, stomatitis, and diarrhea
-cardiac toxicity (can also cause acute chest pain)
-hand-foot syndrome (erythema and possible sensitivity of palms and soles)
-anemia and thrombocytopenia

Front 36

Route of administration of 5-fluorouracil?

Back 36

-must be given IV due to its severe GI tract toxicity and rapid metabolic degradation in the gut and liver
-BUT capecitabine = new orally active form that can treat metastatic breast cancer and colorectal cancer

Front 37

Category/use of cytarabine?

Back 37

Antimetabolite (pyrimidine analog) that is s-phase specific
-ara-C converted to ara-CMP (by deoxycytidine kinase), which is then converted to ara-CTP, which competes with dCTP for incorporation into DNA. Its incorporation into DNA leads to premature DNA chain termination
-best drug available to treat AML
-also treats ALL and blast-phase CML

Front 38

Toxicity of cytarabine?

Back 38

-severe myelosupression (leukopenia, thrombocytopenia, and anemia)
-GI tract toxicity (ulceration, stomatitis, and diarrhea)

Front 39

Category/use of gemcitabine?

Back 39

Antimetabolite (pyrimidine analog) that is not cell cycle specific.
-dFdC is converted to dFdCMP by deoxycytidine kinase, and then dFdCMP is converted to either dFdCDP or dFdCTP
-dFdCDP inhibits ribonucleotide reductase, effectively decreasing the pool of deoxyribonucleotides available for DNA syn
-dFdCTP gets incorporated into DNA and results in the premature termination of DNA synthesis
-first-line treatment for pancreatic carcinoma
-treats non-small cell lung cancer, esophageal, ovarian, bladder, and head and neck cancer

Front 40

Toxicity of gemcitabine?

Back 40

-myelosupression (leukopenia, thrombocytopenia, and anemia)
-flu-like syndrome

Front 41

Category/use of 6-mercaptopurine?

Back 41

Antimetabolite (purine analog) that must be metabolized by hypoxanthine-guanine phosphoribosyl transferase (HGPRT) to the ribonucleotide 6-thioinositic acid (TIMP)
-TIMP inhibits the first step of the de novo syn of the purine base, blocks the formation of AMP and xanthylinic acid from inositic acid, and is converted to thio-guanine ribonucleotides, which are incorporated into DNA and RNY and inhibit DNA/RNA synthesis
-used mainly to maintain remission in ALL patients

Front 42

What drug commonly interacts with 6-mercaptopurine and in what manner?

Back 42

-Allopurinol, which is often given to decrease hyperuricemia in cancer patients receiving chemo
-Allopurinol inhibits xanthine oxidase and thereby elevates plasma levels of mercaptopurine, so patients taking allopurinol should be given decreased doses of 6-mercaptopurine

Front 43

Toxicity of 6-mercaptopurine?

Back 43

-myelosuppression
-hepatotoxicity with prolonged use

Front 44

Mechanisms of resistance of 6-mercaptopurine?

Back 44

-decreased expression of HGPRT (leading to less conversion of 6-MP to the active nucleotide form)
-decreased drug transport

Front 45

Category/use of dactomycin (actomycin D)?

Back 45

DNA intercalating agent that inserts itself between G-C DNA base pairs and forms a stable complex
-interferes with DNA-dependent RNA polymerase causing inhibition of DNA transcription
-causes ss DNA breakage
-mainly used to treat pediatric tumors (Wilms' tumor, rhabdomyosarcoma, and Ewing's sarcoma)
-also treats choriocarcinoma

Front 46

Toxicity of dactomycin?

Back 46

-anorexia, nausea, vomiting
-myelosuppression (pancytopenia)

Front 47

Category/use of daunorubicin?

Back 47

-DNA intercalating agent (anthracycline) that is reduced to intermediates that donate e- to O2 to form superoxide, which then reacts with itself to form H2O2, which is cleaved in the presence of Fe to form the hydroxyl radical that cleaves DNA.
-treats AML

Front 48

Category/use of doxorubicin?

Back 48

-DNA intercalating agent (anthracycline) that is reduced to intermediates that donate e- to O2 to form superoxide, which then reacts with itself to form H2O2, which is cleaved in the presence of Fe to form the hydroxyl radical that cleaves DNA.
-treats sarcoma, breast and lung carcinomas, and malignant lymphomas

Front 49

Category/use of idarubicin?

Back 49

-DNA intercalating agent (anthracycline) that is reduced to intermediates that donate e- to O2 to form superoxide, which then reacts with itself to form H2O2, which is cleaved in the presence of Fe to form the hydroxyl radical that cleaves DNA.
-Treats AML

Front 50

Category/use of epirubicin?

Back 50

-DNA intercalating agent (anthracycline) that is reduced to intermediates that donate e- to O2 to form superoxide, which then reacts with itself to form H2O2, which is cleaved in the presence of Fe to form the hydroxyl radical that cleaves DNA.
-treats gastric cancer and breast cancer

Front 51

Toxicity of anthracycline antibiotics?

Back 51

-myelosuppression (neutropenia)
-irreversible dose-dependent cardiotoxicity
-stomatitis, GI disturbances, and alopecia

Front 52

Category/use of bleomycin?

Back 52

-DNA intercalating agent (antitumor antibiotic) that contains a mix of 2 copper-chelating peptides obtained from streptomyces.
-binds to DNA and induces ss and ds DNA breaks following oxidation and free-radical formation
-treats testicular cancer, squamous cell carcinoma, and lymphomas

Front 53

Toxicity of bleomycin?

Back 53

-pulmonary toxicity (pulmonary fibrosis0
-cutaneous toxicity (erythema, hyperkeratosis, erythema)
-hyperthermia, headache, nausea, and vomiting
-NOTE: causes minimal myelosuppression and immunosuppression and is therefore often used in combo therapy regimens

Front 54

Which antitumor antibiotic causes minimal myelosuppression and immunosuppression?

Back 54

Bleomycin

Front 55

Category/use of vinblastine?

Back 55

Microtubule inhibitor (vinca alkaloid) that binds tubulin and blocks its ability to polymerize into microtubules --> mitotic arrest in M phase --> cell death
-treats metastatic testicular tumors in combo with bleomycin and cisplatin
-pt of ABVD combo regimen to treat Hodgkin's disease

Front 56

Category/use of vincristine?

Back 56

-Microtubule inhibitor (vinca alkaloid) that binds tubulin and blocks its ability to polymerize into microtubules --> mitotic arrest in M phase --> cell death
-treats childhood ALL
-treats Hodgkin's and non-Hodgkin's lymphomas

Front 57

Toxicity of vinblastine?

Back 57

-myelosuppression
-nausea and vomiting

Front 58

Toxicity of vincristine?

Back 58

-dose-limiting neurotoxicity (peripheral neuropathy)
-Note: relatively low bone marrow toxicity!

Front 59

Which microtubule inhibitor has relatively low bone marrow toxicity?

Back 59

Vincristine

Front 60

Category/use of paclitaxel?

Back 60

Microtubule inhibitor (taxane) that blocks microtubule disassembly (promotes assembly of and stabilizes microtubules)
-originally isolated from the bark of the slow-growing pacific yew
-treats ovarian, metastatic breast, head and neck, and lung cancers

Front 61

Category/use of docetaxel?

Back 61

Microtubule inhibitor (taxane) that blocks microtubule disassembly (promotes assembly of and stabilizes microtubules)
-originally isolated from the bark of the slow-growing pacific yew
-treats ovarian, metastatic breast, head and neck, and lung cancers
-treats hormone-refractory prostate cancer

Front 62

Toxicity of paclitaxel?

Back 62

-neutropenia
-peripheral neuropathy
-hypersensitivity reactions

Front 63

Toxicity of docetaxel?

Back 63

-neutropenia
-peripheral neuropathy
-hypersensitivity reactions

Front 64

Mechanisms of resistance to vinca alkaloids?

Back 64

-amplification of p-glycoprotein
-mutations in tubulin leading to decreased binding of the drugs to their target

Front 65

How does p-glycoprotein facilitate drug resistance?

Back 65

p-glycoprotein makes up the 6 membrane-spanning loops of a central transmembrane channel used for the ATP-dependent pumping of drugs from a cell
-can work against vincristine, vinblastine, doxorubicin, bleomycin, etoposide, and others

Front 66

Category/use of etoposide?

Back 66

-Topoisomerase inhibitor (epipodophyllotoxin) that inhibits topoisomerase II, leading to DNA damage
-broad spectrum of use
-treats testicular carcinoma, lung cancer, and non-Hodgkin's lymphoma

Front 67

Category/use of teniposide?

Back 67

-Topoisomerase inhibitor (epipodophyllotoxin) that inhibits topoisomerase II, leading to DNA damage
-treats ALL

Front 68

Toxicity of etoposide?

Back 68

-neutropenia
-oral mucositis

Front 69

Toxicity of teniposide?

Back 69

-neutropenia
-oral mucositis

Front 70

Category/use of irinotecan?

Back 70

-Topoisomerase inhibitor (Camptothecin analog) that inhibits topoisomerase I, leading to ss DNA breaks
-used to treat advanced colorectal cancer, along with lung, ovarian, cervical, and brain tumors

Front 71

Category/use of topotecan?

Back 71

-Topoisomerase inhibitor (Camptothecin analog) that inhibits topoisomerase I, leading to ss DNA breaks
-treats small-cell lung cancer and ovarian cancer

Front 72

Toxicity of irinotecan?

Back 72

-severe neutropenia
-severe diarrhea

Front 73

Toxicity of topotecan?

Back 73

-severe neutropenia
-severe diarrhea

Front 74

Which chemo drugs have mild emetic potential?

Back 74

-flurouracil
-methotrexate
-etoposide
-vincristine
-bleomycin

Front 75

Which chemo drugs have moderate emetic potential?

Back 75

-cyclophosphamide
-doxorubicin
-carboplatin
-mitomycin
-asapraginase
-azacytidine

Front 76

Which chemo drugs have strong emetic potential?

Back 76

-cisplatin
-mechlorethamine
-streptozocin
-dacarbazine
-carmustine
-dactinomycin

Front 77

What type of hormones are given to treat lymphomas and leukemias?

Back 77

Glucocorticoids (prednisone and dexamethasone)

Front 78

Category/use of prednisone?

Back 78

-Hormone given to treat leukemias and lymphomas
-Inhibit mitosis in lymphocytes
-treats ALL, multiple myeloma, and CLL
-part of MOPP and CHOP combo regimens to treat Hodgkin's and non-Hodgkin's lymphomas

Front 79

Toxicity of glucocorticoids?

Back 79

-relatively well-tolerated
-do not induce myelosuppression

Front 80

Category/use of dexamethasone?

Back 80

Hormone given to treat leukemias and lymphomas
-Inhibit mitosis in lymphocytes
-used in combination with radiation therapy to decrease edema related to brain and spinal cord tumors

Front 81

Category/use of tamoxifen?

Back 81

Hormone (Selective Estrogen Receptor Modulator) that acts as an estrogen antagonist (competes with estrogen for binding to the estrogen receptor)
-treats ER positive metastatic breast cancer or as adjuvant therapy after a primary breast tumor excision
-also used to prevent breast cancer in high-risk patients

Front 82

Method of administration of tamoxifen?

Back 82

taken orally (readily absorbed)

Front 83

Toxicity of tamoxifen?

Back 83

-hot flushes, vomiting, hair loss, nausea
-increased risk of endometrial cancer
-increased risk of thromboembolic events

Front 84

Category/use of fulvestrant?

Back 84

-Hormone (Selective Estrogen Receptor Downregulator) that tightly binds to the estrogen receptor and inhibits its dimerization and increases its degradation.
-Ultimately reduces the number of estrogen receptor molecules in cells
-Treats postmenopausal women with ER-positive metastatic breast cancer

Front 85

Category/use of aminoglutethamide?

Back 85

Hormone (aromatase inhibitor) that inhibits the activity of aromatase (rather weakly) and thus decreases estrogen levels.
-Has significant toxicity
-this first generation A.I. has since been replaced by 3rd generation A.I.s
-treats breast cancer

Front 86

Category/use of anastrozole?

Back 86

Hormone (non-steroidal aromatase inhibitor) that strongly, selectively, and reversibly inhibits the action of aromatase, and thus decreases estrogen levels
-third generation A.I.
-treats ER-positive breast cancer in postmenopausal women

Front 87

Which is more toxic, anastrozole or aminoglutethamide?

Back 87

aminoglutethamide (this is a first generation aromatase inhibitor, which has since been replaced by anastrozole, a third generation A.I.)

Front 88

Name four major aromatase inhibitors

Back 88

-aminoglutethamide
-anastrozole
-letrozole
-exemestane

Front 89

Category/use of letrozole?

Back 89

-Hormone (non-steroidal aromatase inhibitor) that strongly, selectively, and reversibly inhibits the action of aromatase, and thus decreases estrogen levels
-third generation A.I.
-treats ER-positive breast cancer in postmenopausal women

Front 90

Category/use of exemestane?

Back 90

-Hormone (steroidal aromatase inhibitor) that strongly, selectively, and irreversibly inhibits the action of aromatase (by competing with its natural substrate androstenedione), and thus decreases estrogen levels
-third generation A.I.
-treats ER-positive breast cancer in postmenopausal women

Front 91

Which drugs are currently given as first-line therapy for postmenopausal ER+ breast cancer?

Back 91

aromatase inhibitors (have replaced tamoxifen in recent history)

Front 92

Category/use of leuprolide?

Back 92

Hormone (GnRH analog) that binds to the GnRH receptor and inhibits the release of FSH and LH --> decreased testicular production of testosterone
-does NOT inhibit adrenal androgen synthesis
-treats prostate cancer

Front 93

Category/use of goserelin?

Back 93

-Hormone (GnRH analog) that binds to the GnRH receptor and inhibits the release of FSH and LH --> decreased testicular production of testosterone
-does NOT inhibit adrenal androgen synthesis
-treats prostate cancer

Front 94

Category/use of flutamide?

Back 94

Hormone (non-steroidal androgen receptor blocker) that competes with androgens for binding to the androgen receptor and prevents its translocation into the nucleus
-inhibits adrenal androgen synthesis
-treats prostate cancer

Front 95

Category/use of bicalutamide?

Back 95

Hormone (non-steroidal androgen receptor blocker) that competes with androgens for binding to the androgen receptor and prevents its translocation into the nucleus
-inhibits adrenal androgen synthesis
-treats prostate cancer

Front 96

Category/use of hydroxyurea?

Back 96

-inhibits ribonucleotide reductase (which catalyzes the conversion of deoxyribonucleotides to ribonucleotides)
-treats myeloproliferative disorders (CML, polychthemia vera, essential thrombocytopenia)
-treats sickle cell disease

Front 97

Category/use of all-trans retinoic acid?

Back 97

-Retinoid that induces differentiation in leukemic promyelocytes
-treats AML

Front 98

Category/use of arsenic trioxide?

Back 98

-A heavy metal toxin
-effectively treats relapsed APL

Front 99

Category/use of thalidomide?

Back 99

-inhibits IL-6 production (which is a growth factor for multiple myeloma)
-inhibits TNFalpha signaling (and thus exerts an immunomodulatory effect)
-exhibits antiangiogenic activity
-activates the apoptotic pathways
-causes short-limb birth defects if given to pregnant women (used to be administered for morning sickness)
-treats multiple myeloma and myelodysplastic syndromes

Front 100

Category/use of interferon alpha?

Back 100

-Interferon used to treat hairy-cell leukemia, CML, and AIDS-related Kaposi's sarcoma

Front 101

Category/use of Imatinib?

Back 101

Tyrosine kinase inhibitor that inhibits Abl kinase (also inhbits PDGFR and c-kit)
-aka Gleevec
-first line therapy for treating CML
-treats GI tumors

Front 102

Category/use of gefitinib?

Back 102

-aka Iressa
-Tyrosine kinase inhibitor that inhibits epidermal growth factor receptor (EGFR) tyrosine kinase
-treats non-small cell lung cancer

Front 103

Category/use of erlotinib?

Back 103

-aka Tarceva
-Tyrosine kinase inhibitor that inhibits epidermal growth factor receptor (EGFR) tyrosine kinase
-treats non-small cell lung cancer

Front 104

Category/use of rituximab?

Back 104

-Monoclonal antibody against the B cell marker CD20
-treats non-Hodgkin's lymphomas

Front 105

Category/use of trastuzumab?

Back 105

-aka Herceptin
-humanized monoclonal antibody against the HER2/neu (Erb2)
-treats HER2/neu-overexpressing metastatic breast cancer

Front 106

Category/use of cetuximab?

Back 106

-Monoclonal antibody against the EGFR1 (Erb1)
-approved for the treatment of EGFR-positive metastatic colorectal cancer