Antineoplastic Agents

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How do alkylating agents work?: Cross link DNA

They are NOT phase specific

Cells must be proliferating
Nitrogen Mustard are alkylating agents. Name the important ones (5): Mechlorethamine
Cyclophosphamide
Ifosfamide
Melphalan
Chlorambucil
Cyclophosphamide indications (3): NHL
breast and ovarian carcinoma
also an immunosupressant
Cyclophosphamide SE: hemmorhagic cystitis
myelosuppression
How do you avoid hemorrhagic cystitis?: MESNA and adequate hydration
What is the MOA of busulfan? Clinical use? Major SE?: alkylating agent

CML

pulmonary fibrosis and hyperpigmentation
Nitrosoureas are alkylating agents. Name 4 of them.: Carmustine
Lomustine
Semustine
Streptozocin
Nitrosoureas CI? Major SE?: Brain tumors (we must preserve the brain)
Streptozocin - pancreaitic islet cell tumor

CNS toxicity
What type of agent is cisplatin? Indication? SE?: Alkylating agent

Testicular, bladder, ovary, lung

Nephrotoxicity and ototoxicity
The Mopp regimen is used for Hodgkins, what comprises MOPP?: Mechlorethamine -alkylating agent
Oncovin (vincristine)- vinca alkaloid
procarbazine - alkylating agent
prednisone
Name an acute SE of procarbazine: disulfiram-like effect
Are antimetabolites phase specific?: Yes, S phase
Methotrexate (MTX) MOA (be specific): folic acid analog

inhibits dihydrofolate reductase

thus decreasing dTMP
Whate rescues normal cells from MTX toxicity?: Leucovorin
Neoplastic use of MTX (4): leukemia (childhood ALL)
lymphoma
sarcoma
choriocarcinoma
Non-Neoplastic use of MTX (4): psoriasis
RA
abortion
ectopic pregnancy
MTX SE (2): myelosuprresion (reversible with Luke)

hepatotoxicity (macrovesicular fatty change)
5-FU is an anti-metabolite MOA?: complexes w/ THF

inhibits thymidyalte synthetase

decreses dTMP
5-FU clinical use? (2) SE? (2): metastatic colon cancer
basal cell carcinoma (topical)

myelosuppression
(LUKE will actually increase GI toxicity so never use)
photosensitivity
What is cytarabine (Ara-C)? MOA?: an anitmetabolite

pyrimidine analog

inhibits DNA polymerase
Cytarabine clinical use? SE?: AML (w/ daunorubicin)

Leukopenia
Thrombocytopenia
Megaloblastic anemia
6-mercaptopurine (6-MP) Clinical use (be specific)? SE?: leukemia (main. of child ALL; not useful with CLL)
NHL

myelosuppresson
cholestatic jaundice
What increases 6-MP toxicity and why?: allopurinol

both metabolized by xanthine oxidase
Name some anitmetabolites used against hairy cell leukemia (3): Pentostatin
Fludarabine
Cladribine
Name two non-neoplastic agents that are related to purine analogs and their clinical uses?: Azathiopurine - immunosuprression w/ transplants

Allopurinol - hyperuricemia/gout
(an inhibitor of xanthine oxidase)
When is allopurinaol useful in neoplastic disease?: tumor lysis syndrome
(rapid cell lysis leads to release of purines which could lead to renal stones/failure)
Vincristine and Vinblastine (Vinca alkaloids) phase specfic? MOA?: M phase

bind tubulin and inhibit MT polymerization
Clinical uses of Vinblastine and Vincristine: MOPP for lymphoma
Wilms
choriocarcinoma
SE of vincristine? (3) SE of vinblastine?: neurotoxicity
peripheral neuropathy
paralytic ileus

myelosuppression
Etoposide phase? MOA?: G2 phase

inhibits topoisomerase II thus double strand breaks remain
Etoposide use?: Oat cell carcinoma of lung and prostrate
testicular carcinoma
Paclitaxel (Taxol) phase? source? MOA?: M phase

Yew tree

stabilizes MT in mititic apparatus thus preventing depolymerization
What is the only antibiotic neoplastic that is phase specific?: Bleomycin
(G2 and M phase)
Dactinomycin (Actinomycin D) MOA? uses? (4): intercalates and inhibits RNA poly

Wilms
Ewings
Rhabdomyosarcoma
Kaposi
Doxorubucin (Adriamycin) MOA? SE?: intercalates and form strand breaks

Cardiotoxicity
(rubicin sisters will break your heart)
Clinical uses of Doxorubucin? (6): Hodgkins
myelomas
sarcomas
solid tumors (breast, kidney, lung)
Hodgkins can be treated with the ABVD regimen which is?: Adriamycin (doxorubucin)
Bleomycin
Vinblastine
Dacarbazine
Bleomycin MOA? Use? SE?: intercalates and causes strand breaks

testicular cancer

pulmonary fibrosis
Name a chemotherapeutic agent increases the cardiotoxicity of doxorubicin?: Mitomycin
Prednisone MOA? Use?: suppress mitosis and possibly induce apoptosis

MOPP
CLL
breast carcimoma (decreases estrogen)
Prednisone SE (9): Cushing-like symptoms
immunosuprression
cataracts
acne
osteoporosis
HTN
peptic ulcers
hyperglycemia
psychosis
Use of hydroxyprogesterone, medoxyprogesterone, and megestrol? (3): endometrial carcimoma
breast cancer
prostrate cancer
Use of androgens (testosterone and fluoxymesterone)?: estrogen receptor positive breast carcinoma (only in pre and post-meno)
Flutamide and bicalutamide MOA? use?: androgen receptor antagonist

prostate cancer
Leuprolide and goserelin MOA? Use?: analog of LH-RH and blocks GnRH thus decreasing androgen synthesis

prostrate carcinoma
ethinyl estradiol, DES, estramustine use?: advanced prostrate carcinoma
Tamoxifen/Raloxifene MOA? use?: partial agonist of estrogen receptor

breast cancer
Tamoxifen/Raloxifene SE? (2): induce endometrial carcinoma
hot flashes
anastrozole MOA? use?: inhibits aromatase

tamoxifen R breast carcinoma
IFN use (3) SE?: hairy cell leukemia
Karposi
genital warts

flu-like syndrome
adesleukin is what? use? (2) SE?: IL-2

metastatic melanoma
renal cell carcinoma

severe HTN and cardiovascular toxicity (life threatening)
L-Asparaginase use and w/ what other agents?: ALL

vincristine
prednisone
hydroxyurea MOA? phase? use?: inhibits ribonucleotide reductase thus deoxyribonucleotides cant be produced

S phase

CML
Topotecan and Irinotecan MOA? use (different for each one?: inhibit topoisomerase I

used after 1st line treatment failure for:
topotecan - ovarian carcinoma
irinotecan - colorectal carcinoma

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Deck Info

Number of cards 54