Antineoplastics

Front 1

Mechlorethamine

Back 1

- IV nitrogen mustard (CCNS)
- DNA alkylating agent → cross-linking of DNA strands, strand breakage, and miscoding
- Causes hyperuricemia → administer with allopurinol

Front 2

Cyclophosphamide

Back 2

- Oral/IV/IM/IP nitrogen mustard (CCNS)
- One of the most widely used antineoplastic drugs → used for cancers and autoimmune disease
- DNA alkylating agent → cross-linking of DNA strands, strand breakage, and miscoding
- Causes hemorrhagic cystitis and bladder transitional cell carcinoma → administer with MESNA and large fluid volumes

Front 3

Ifosfamide

Back 3

- IV nitrogen mustard pro-drug (CCNS)
- DNA alkylating agent → cross-linking of DNA strands, strand breakage, and miscoding
- Causes hemorrhagic cystitis and bladder transitional cell carcinoma → administer with MESNA and large fluid volumes

Front 4

Thiotepa

Back 4

- IV ethylenimine nitrogen mustard (CCNS)
- DNA alkylating agent → cross-linking of DNA strands, strand breakabe, and miscoding

Front 5

Carmustine

Back 5

- IV nitrosurea (CCNS)
- DNA alkylating agent → cross-linking of DNA strands, strand breakage, and miscoding
- Can penetrate CNS
- Severe myelosuppression, with nadir at 6 weeks

Front 6

Dacarbazine

Back 6

- IV monofunctional triazene (CCNS)
- Methylates DNA to inhibit DNA/RNA/protein synthesis
- Used in melanoma
- Severe nausea/vomiting

Front 7

Cisplatin

Back 7

- IV platinum complex (CCNS)
- Alkylates DNA (overall mechanism unknown)
- Used to sensitize patient to radiation therapy
- Multifactorial resistance is major limitation
- Not myelosuppressive
- Causes cumulative renal toxicity in distal tubules → vigorous hydration and diuresis
- Most strongly emetic antineoplastic drug
- Causes ototoxicity/neurotoxicity

Front 8

Carboplatin

Back 8

- IV platinum complex (CCNS)
- Alkylates DNA (overall mechanism unknown)
- Used to sensitize patient to radiation therapy
- Less nausea, neurtoxicity, ototoxicity, and nephrotoxicity than cisplatin
- More myelosuppressive than cisplatin

Front 9

Methotrexate (MTX)

Back 9

- Oral/IV anti-metabolite
- Folic acid analog that competitively antagonizes DHFR → decreased DNA/RNA/protein synthesis
- Resistance via decreased drug transport, increased DHRF, or decreased DHFR affinity
- Myelosuppression > GI toxicity > skin toxicity
- Leucovorin rescue reverses adverse effects

Front 10

6-Mercaptopurine (6-MP)

Back 10

- Oral purine analog
- Converted to inhibitory nucleotide analogs by hypoxanthine-guanine phosphoribosyltransferase (HGPRT) → inhibition of purine interconversion and DNA/RNA synthesis
- Resistance via decreased HGPRT
- Give with allopurinol to prevent hyperuricemia

Front 11

6-Thioguanine (6-TG)

Back 11

- Oral purine analog
- Converted to inhibitory nucleotide analogs by hypoxanthine-guanine phosphoribosyltransferase (HGPRT) → inhibition of purine interconversion and DNA/RNA synthesis
- Resistance via decreased HGPRT
- Give with allopurinol to prevent hyperuricemia

Front 12

5-Fluorouracil (5-FU)

Back 12

- IV nucleotide analog
- Inhibits thymidylate synthase (UMP → TMP) and gets incorporated into RNA
- Good CNS penetration
- Resistance via increased synthesis or decreased affinity of thymidylate kinase
- Can cause severe ulceration of oral/GI mucosa (mucositis) and anorexia
- Also given topically for pre-malignant skin lesions

Front 13

Cytarabine

Back 13

- IV anti-metabolite analog
- Activated to ara-CTP by deoxycytidine kinase → S phase specific
- Resistance via decreased deoxycytidine kinase, increased cytidine deaminase, altered DNA pol, increased dCTP, and decreased transport
- Hepatotoxic and neurotoxic

Front 14

Gemcitabine

Back 14

- IV anti-metabolite
- Pro-drug of pyrimidine analog → inactivates ribonucleotide reductase
- Resistance via unknown mechanism
- > 30% experience flu-like symptoms, anorexia, and skin rash
- 10-29% experience diarrhea, weakness, hair loss, mouth sores, insomnia, and dyspnea

Front 15

Doxorubicin

Back 15

- IV anthracycline
- Intercalates DNA → inhibition of DNA/RNA synthesis and topoisomerase II
- Resistance via P-glycoprotein efflux
- Potentially irreversible, cumulative, dose-related cardiac toxicity
- Causes severe total alopecia and radiation recall (dermatitis in previously radiated area)
- Broad spectrum → one of the most important anticancer drugs

Front 16

Daunorubicin

Back 16

- IV anthracycline
- Intercalates DNA → inhibition of DNA/RNA synthesis and topoisomerase II
- Resistance via P-glycoprotein efflux
- Potentially irreversible, cumulative, dose-related cardiac toxicity
- Causes severe total alopecia and radiation recall (dermatitis in previously radiated area)
- Broad spectrum → one of the most important anticancer drugs

Front 17

Bleomycin

Back 17

- IM/IV glycopeptide
- Binds to DNA as Fe complex that generates ROS
- Minimal myelosuppression
- Dose-dependent non-idiopathic pulmonary fibrosis in 5-10% of patients → 1% fatality that is increased by oxygen
- Also causes delayed skin ulceration at pressure points and stomatitis

Front 18

Vincristine

Back 18

- IV vinca alkaloid (plant product)
- M phase specific → binds tubulin to prevent polymerization/mitotic spindle formation
- MDR and cross-resistance with anthracycline antibiotics
- Dose-limiting peripheral neuropathy → initial sensory impairment and parasthesias of extremities, followed by neuritic pain and loss of DTR; cause ataxia and paralysis

Front 19

Vinblastine

Back 19

- IV vinca alkaloid (plant product)
- M phase specific → binds tubulin to prevent polymerization/mitotic spindle formation
- MDR and cross-resistance with anthracycline antibiotics
- Dose-limiting myelosuppression
- Less alopecia, neurotoxicity and stomatitis than vincristine

Front 20

Paclitaxel

Back 20

- IV yew tree derivative
- Disrupts mitosis by binding to tubulin to stabilize MTs (binds at different tubulin site than vinca alkaloids)
- Resistance via MDR (no cross-resistance with vinca alkaloids)
- Causes myelosuppression, sensory neuropathy, and hypersensitivity

Front 21

Etoposide

Back 21

- IV/oral epidophyllotoxin analog (May apple/American mandrake product)
- Binds tubuline and inhibits topoisomerase II → S/G2 block
- Some penetration of CNS
- Resistance via MDR and altered topoisomerase II
- Causes acute hypotension and delayed hepatotoxicity at high doses

Front 22

Tamoxifen

Back 22

- Oral hormonal therapy
- Primarily used as adjuvant after breast cancer surgery
- Anti-estrogen → binds estrogen receptor to block estrogen-meidated gene transcription
- Resistance via loss of estrogen receptor positive tumor cells
- One of the least noxious anti-neoplastic agents, but 3-flod increase in endometrial cancer and possible tumor flare
- Requires CYP2D6 metabolism to become fully active → avoid SSRIs if possible due to CYP2D6 inhibition; favor citalopram/escitalopram over paroxetine/fluoxetine

Front 23

Leuprolide

Back 23

- IM hormonal therapy
- Used for androgen receptor positive metastatic prostate carcinoma
- GnRH receptor agonist that causes hormonal castration: chronic stimulation → desensitization/downregulation → reduced FSH/LH → reduced testicular androgens
- Resistance via loss of AR dependence by tumor cells
- Can cause tumor flare and hot flashes

Front 24

Goserelin

Back 24

- IM hormonal therapy
- Used for androgen receptor positive metastatic prostate carcinoma
- GnRH receptor agonist that causes hormonal castration: chronic stimulation → desensitization/downregulation → reduced FSH/LH → reduced testicular androgens
- Resistance via loss of AR dependence by tumor cells
- Can cause tumor flare and hot flashes

Front 25

Prednisone

Back 25

- Oral/IV glucocorticioid
- Used for ALL and HL/NHL
- Anti-inflammatory → decreased lymphocyctic replication
- Resistance via loss of functional receptor
- Causes immunosuppression, moon-face, etc.

Front 26

Hydroxyurea

Back 26

- Oral anti-neoplastic
- Inhibits ribonucleoside diphosphate reductase → decreased nucleotides inhibits DNA synthesis
- Resistance via increased or altered ribonucleotide reductase

Front 27

L-Asparigniase

Back 27

- IV anti-neoplastic
- Only used in childhood ALL
- Degrades asparagine to aspartic acid and ammonia → inhibits protein synthesis in tumor cells that have lost ability to synthesize asparagine
- Dose-limiting hepatotoxicity
- Anaphylaxis in 10% of patients

Front 28

Imatinib

Back 28

- Oral tyrosine kinase inhibitor
- DOC for CML and used in gastrointestinal stromal tumors (GIST)
- Inhibits BCR-ABL and cKIT kinase produced by Philadelphia chromosome (t(9;22))
- Low toxicity but may cause fluid retention
- 87% cytogenic response and 89% 5-year survival for CML

Front 29

Thalidomide

Back 29

- Oral anti-neoplastic
- Treat multiple myeloma and myelodysplasia (also used in erythema nodosum leprosum)
- Has anti-angiogenic properties via unknown mechanism
- Teratogen that causes dysmyelia

Front 30

Bevacizumab

Back 30

- IV/intraocular biological response modifier
- Treat colorectal cancer and wet macular degeneration
- Humanized anti-VEGF monoclonal antibody
- Can cause severe hypertension, heart failure, and GI perforation