Anti-Cancer Drugs

Front 1

CYTOTOXIC AGENTS
7 groups
"Chemotherapy"
* kills cell directly

Back 1

1. Alkylating Agents
2. Platinum compounds
3. Anti-metabolites
4. Anti-tumor antibiotics
5. Mitotic inhibitors
6. Topoisomerase inhibitors
7. Miscellaneous

Front 2

Alkylating Agent: CYCLOPHOSPHAMIDE (CYTOXAN)
Cell-cycle nonspecific

Back 2

Uses: BREAST & ovarian CA, solid tumors of head & neck, Non-Hodgkins lymphomas
Action: transfers an alkyl group to DNA interrupting DNA & RNA synthesis making G-G bonds
* Resistance can develop
PO & IV admin
* Toxic to tissues with high growth fraction> BONE MARROW (infection, bleeding, weakness, tiredness, anemia), N/V, alepecia, hemorrhagic cystitis

Front 3

Platinum compound: CISPLATIN (PLATINOL)
Cell-cycle non-specific

Back 3

Uses: Approved for TESTICULAR, ovarian, & bladder; off-label component in standard-of-care regimens for lung, head & neck CAs
Action: forms cross links btwn & w/ in strands of DNA
Given IV
* NEPHRO [minimized w/ extensive hydration, diuretic therapy, and amifostine (Ethyol) & be careful with aminoglycocides], oto [hearing loss], & neurotoxicities, SERVERE N/V [can start w/ in 1 hr of treatment to several days after dosing], bone marrow

Front 4

Anti-Metabolites: 3 classes
1. Folic acid analogs
2. Pyrimidine analogs
3. Purine analogs
> Mostly S phase specific (CCS)
NOTE: Analog defined: person or thing seen as comparable to another

Back 4

FOLIC ACID analogs (in active form, needed for several essential biochemical rxns): works by blocking conversion of folic acid into active form
PYRIMIDINE analogs (cytosine, thymine, & uracil are bases used in the biosynthesis of DNA & RNA): can inhibit creation of pyrimidines, DNA, & RNA; & can undergo incorporation into DNA & RNA disrupting nucleic acid function (all are prodrugs that must be converted into active forms in the body)
PURINE analogs (adenine, guanine, & hypoxanthine are bases used for biosynthesis of nucleic acids): can inhibit creation of purines, DNA, & RNA; & can undergo incorporation into DNA & RNA disrupting nucleic acid function (note also used for immunosuppression, antiviral therapy, & gout)

Front 5

Folic acid analog: METHOTREXATE [Rheumatrex, Trexall]
S-phase specific (CCS)

Back 5

Action: inhibits dihydrofolate reductase [the enzyme that converts dihydrofolic acid (FH2) into tetrahydrofolic acid (FH4), which is a necessary step in activating folic acid that is needed for biosynthesis of essential cellular constituents (DNA, RNA, & proteins)] & also fall in thymidine levels is a potent signal that induces apoptosis (programmed cell death)
PO, IM, & IV
Uses: Non-Hodgkins lymphoma, ALL (Acute lymphoblastic leukemia), osteogenic sacroma, RA (rheumotoid arthritis), psoriasis
BONE MARROW DEPRESSION, stomatitis, GI ulceration, N/V, & high dose damages kidneys [BUN (7-20 mg/dL) & creatinine (M 0.5-1.5 & W 0.6-1.2)]
NOTE: Leucovotin rescue enhances effectiveness

Front 6

Pyrimidine analog: FLUROURACIL or FU5 (Adrucil)
Drug employed to extensively treat solid tumors
S phase specific

Back 6

Action: inhibits pyrimidines (cytosine, thymine, uracil), in order to be effective fluorouracil must be converted into its active (which occurs only during cell cycle) form, 5-fluoro2'-deoxyuridine-5'-monophosphate (FDUMP), FDUMP inhibits thymidylate synthetase depriving cells of thymidylate needed to make DNA
- shows some S-phase specificity
Continuous IV
Uses: adjuvant (applied after initial treatment for cancer, esp. to suppress secondary tumor formation) tx of colon & breast CAs w/ other drugs; & in palliative therapy of stomach & pancreatic CAs; & tx of pre-malignant keratoses topically
NEUTROPENIA, GI ULCERATION-STOP DRUG IF STOMATITIS OR DIARRHEA, hand foot syndrome (neuropathies or tingling/burning & redness, swelling, blistering), alopecia, hyperpigmentation

Front 7

Anti-metabolite: Purine analog MERCAPTO-PURINE (purinethol)
Prodrug
S-phase specific (CCS)

Back 7

Action: disrupts multiple biochemical processes, including purine biosyntheses, nucleotide interconversion, & biosynthesis of nucleic acids
Resistance mechanisms: reduced activation of drug & accelerated deactivation
PO admin. doesn't reach CNS
Uses: acute lymphocytic leukemia
BONE MARROW DEPRESSION, hepatic dysfunction-30% of pts (elevations in bilirubin & transaminases), N/V, oral/intestinal ulcers
Concurrent use of allopurinol increases risk of toxicity
Mutagenic-avoid pregnancy

Front 8

Anti-tumor antibiotic: DOXORUBICIN (ADRIAMYCIN)
CCNS
An anthracycline
Harmless red color to body fluids

Back 8

Action: intercalation w/ DNA (slipping in btwn base pairs distorting DNA structure) & when bound to DNA it forms a complex w/ toposicomerase 2 (enzyme that repairs DNA strands) inhibiting DNA repair
IV infusion (vesicant), doesn't cross blood brain barrier
Uses: BREAST, ovarian, lung, stomach, testicular, thyroid CAs, w/ Hodgkins & non-Hodgkins lymphomas
Side effects: acute & delayed injury to heart (look at serum BNP & MUGA scan) (dysrthymias & EKG changes) [DEXRAZOXANE (ZINECARD) can protect heart but must become active where drug binds to iron preventing it from interacting w/ doxorubicin; but causes severe myelosuppresion & may reduce anti-CA effects- only approved for pts receiving tx for breast CA][ACE inhibitors (ramipril) can prevent cardiac damage if given early], BONE MARROW SUPPRESSION (70% of pts), stomatitis, alopecia

Front 9

Mitotic inhibitor: Vinca alkaloid (derived from Vinca rosea-the periwinkle plant): VINCRISTINE (Oncovin, Vincasar)
M-phase specific (CCS)- blocks mitosis during metaphase

Back 9

Action: blocks mitosis by disrupting assembly of micrtotubles (filament that move chromosomes during cell division) by binding w/ tubulin (major component of microtubles) in absence of microtubles, cell division ends at metaphase (metaphase block-potent signal for apoptosis or programed cell death)
IV- vasicant (penetration to CNS is poor)
Uses: Hodgkins & non-Hodgkins lymphomas, actute lymphocyctic leukemia (ALL), Wilms' tumor, rhabdomyosarcoma, kaposi's sarcoma, breast & bladder CA
PERIPHERAL NEUROPATHY, causes little to no damage to bone marrow

Front 10

Mitotic inhibitor: Taxane: PACLITAXEL (TAXOL)
M-phase (CCS)

Back 10

Action: acts during late G2 & M phase to promote formation of stable microtuble bundles inhibiting cell division & producing apoptosis
Uses: Often combined w/ cisplatin (1st line therapy) for ovarian & lung CAs who are not candidates for curactive surgery & radiation) & used in combo w/ doxorubicin for breast CA
IV- doesn't go to CNS
SEVERE HYPERSENSITIVITY RXN (hypotension, dyspnea, angioedema, urticaria)- premed w/ steroids, benadryl & cimetidine, BONE MARROW DEPRESSION, neuropathy, bradycardia (can lead to 2nd or 3rd degree heart block or MI), sudden alopecia of all body hair

Front 11

Topoisomerase inhibitor: ETOPOSIDE (VePesid)
CCS-G2 phase
NOTE: topoisomerases are nuclear enzymes that alter the shape (topology) of supercoiled DNA, w/ out action of topoisomerase the double helix would become too tangled to permit DNA replication, RNA synthesis, or DNA repair

Back 11

Action: cut into DNA strand-which permits the strand to relax in vicinity of the cut & then they later reseal the cut (cells in S & G2 phase are most sensitive)
Uses: refractory testicular & small cell lung CAs
PO & IV- plasma protein binding is high, penetration to CNS is low
BONE MARROW SUPPRESION, alopecia, N/V, mucositis, hypotension

Front 12

CCNS

Back 12

Alkylating agents
Antibiotics
Nitrosoureas

Front 13

CCS

Back 13

Steriods
Antimetabolites
Podophyllotoxins
Taxanes or taxoids
Vinca alkaoids

Front 14

Anti-estrogen: TAMOXIFEN (NOLVADEX)
Selective estrogen receptor modulators

Back 14

Blocks estrogen receptors in breast CA cells
Activates estrogen receptors in bone
Side effects: hot-flashes, weight gain, endometrial CA

Front 15

Anti-estrogen: Aromatase inhibitor: ANASTROZOLE (ARIMIDEX)

Back 15

Blocks estrogen from adrenal glands
Side effects: joint/muscle pain

Front 16

Hormonal agent for advanced prostate CA

Gonadotropin releasing hormone agonist: LEUPROLIDE (LUPRON)

Back 16

Action: suppresses androgen production by testes
"chemical castration"
Side effects: hot flases, gynecomastia, osteoprosis

Front 17

Androgen receptor blocker: FLUTAMIDE (EULEXIN)

Back 17

Action:used w/ GnRH to reduce CA "flare"; blocks effects of adrenal androgens
Side effects: hot flashes, gynecomastia, osteoprosis

Front 18

Hormonal agent: adjuvant
Glucocorticoids

Back 18

Uses: lymphocytic leukemia, lymphomas
High dose- GI ulceration, osteoporosis, adrenal insufficiency
Benefits: treats, N/V, reduces cerebral edema, relieves pain from inflammation, suppresses hypercalcemia, improves mood, causes weight gain

Front 19

Targeted Drugs (4 groups)

Back 19

1. EGFR- Tyrosine Kinase inhibitors
2. CD20- Directed antibodies
3. Angiogenesis inhibitors
4. HER-2 receptor blockers

Front 20

Targeted Drug

EGFR- Tyrosine Kinase inhibitor
CETUXIMAB (ERBITUX)

Back 20

Uses: colorectal, head/neck CAs
Action: blocks epidermal growth factor receptors
SEVERE INFUSION RXN

Front 21

Targeted drug

CD20 Directed antibody:
RITUXIMAB (RITUXAN)

Back 21

Uses: non-Hodgkins lymphoma
Action: targets CD20 antigens present on surface of B cells; antigen/antibody binding causes immune response against B cell

Front 22

Targeted drug:

Angiogenesis inhibitor: BEVACIZUMAB (AVASTIN)

Back 22

"no flow, no grow"
Uses: colorectal CA

Front 23

Targeted drug

HER-2 receptor blocker: TRASTUZUMAB (HERCEPTIN)

Back 23

Uses: breast CA
Action: blocks human epidermal growth factor receptors

Front 24

Hematopoietic growth factor- RBCs

Back 24

ERYTHROPOIETIN
1. EPOGEN
2. PROCRIT
3. ARANESP

Front 25

Hematopoietic growth factor- WBCs

Back 25

GRANULOCYTE-COLONY STIMULATING FACTOR
1. NEUPOGEN
2. NEULASTA

Front 26

Thrombopoietic growth factor- platelets

Back 26

NEUMEGA

Front 27

Managing N/V Meds

Back 27

1. Aprepitant (Emend)
2. Dexamethasone
3. Ondasetron (Zofran)
4. Granisetron (Sancuso)- patch, up to 5 days relief
5. Dronabinol (Marinol)- synthetic marijuana