Antineoplastics

• Antimetabolites:
• Methotrexate
• 5-FU
• Cytarabine
• Mercaptopurine
• Hydroxyurea
• Pentstatin

Bleomycin

• Vincristine
• Vinblastine
• Paclitaxel

• Dactinomycin
• Tamoxifen

• Etoposide
• dactinomycin

Cell Cycle Specific - act at specific phases of cell cycle

• Cell cycle not specific
• Act on both dividing and non-dividing cells

Both CCS and CCNS

• Cytarabine (pyrimidine antagonist(Sphase )
• Fluorouracil(pyrimidine antagonist)(S phase)
• Mercatpopurine (purine antagonist)(S phase)
• Methotrexate (antimetabolite) (S phase)
• Thioguanine (Purine antagonist) (S phase)

• Cyclophosphamide
• busulphan
• chlorambucil
• cisplatin/carboplatin
• oxaliplatin
• Lomustine

• doxorubicin
• daunorubicin
• dactinomycin

• Drugs or irradiation that kills a constant population of cells in a population.
• Pulses of treatment separated by recovery intervals of fixed duration.

• Bone marrow: methotrexate
• kidney: cisplatin
• heart: doxorubicin
• nervous tissue: vincristine

• Change in senestivity of gene product
• change in target receptor affinity characteristics
• change in expression of drug transporter glycoprotein(Pgp or MDR-1)
• modification in the prodction of drug inactivating enzymes
• Inc DNA repair reducing damage
• red activation of drugs
• alteration in the P53 pathway

• CMF
• Cyclophosphamide (1-14)
• Methotrexate (1&8)
• 5-Fluorouracil (1 & 8)

• FOLFOX
• Fluorouracil
• leucovorin
• oxaliplatin

cisplatin and paclitaxel

• PVB
• cisplatin
• Vinblastine
• Bleomycin

• CHOP
• cyclophosphamide
• doxorubicin(hydroxyldaunorubicin)
• Vincristine (Oncovorin)
• Prednisone

• MOPP
• Mechlorethamine
• vincristine(Oncovorine)
• Prednisone
• Procrbazine

• ABVD
• Doxorubicin (Adriamycin)
• Bleomycin
• Vinblastine
• Dacarbazine

• 1) BM- pancytopenia
• 2) Gonads - red in # of germ line cells
• 3) GIT- red in rate of renewal
• 4) Skin- bases of hair follicles --> alopecia
• 5) Renal- hyperuricemia, hypercalcemia, hyperkalemia, & destruction of renal tissue
• 6) CRTZ & VC - severe vomiting may occur
• 7) Nerve damage

• aprepitant
• dexamethzaone
• ondansetron

• dexamethazone
• ondansetron

• dexamethazone
• metochlopramide
• prochlorperazine

• methotrexate
• 5-fluorouracil

• cyclophosphamide
• cisplatin

• doxorubicin
• daunorubicin
• bleomycin

• vincristine
• vinblastine
• paclitaxel

• tamoxifen
• anastrozole
• trastuzumab
• prednisone

asparaginase

trastuzumab

cisplatin

Imatinab mesylate aka (tyrosine kinase inhibitor)

• Antimetabolite
• Used: AML
• MOA: DNA strand elongation
• A/E neurotoxic

• Oral prodrug -> 5-fluorouracil
• MOA: inhibits thymidylate synthase
• USED: paclitaxel and doxorubicin- resistant patients with colorectal or metastatic breast cancer.

• Aklylating agent
• A/E: toxic to the CNS
• USED- CNS cancer

• MOA: stabilizes the topoisomerase II- DNA complex causing double strand DNA breaks during DNA replication.
• DOSE LIMITING LEUKOPENIA

• MOA: Topoisomerase 1 inhibitor, preventing religation of bits helices; causes accumulation of single stranded breaks in DNA.
• DOSE LIMITING NEUTROPENIA
• antiestrogen for hormone-sensitive tumors.

Nonsteroidal androgen antagonist - inhibits the translocation of steroid receptors to the nucleus.

• 5-alpha reducatase inhibitor that inhibits synthesis of dihydrotestosterone.
• Both used to treat prostate cancer.

• GnRH analogues- act as a partial agonist at GnRH receptors. At constant doses inhibits the release of LH and FSH.
• USED: treatment of prostate cancer

• unconjugated chimeric antiCD20 monoclonal antibody which binds to the CD20 antigen on follicular B cells in Non Hodgkins lymphoma.
• USED: severe Crohn's disease especially with fistulation.

MOA: inhibits bcr-abl tyrosin kinase found in chronic myelocytic leukemia.

• Class: Antimalignant/ antimetabolite
• USE: Solid Tumors
• ALL
• immunosuppressive
• RA// SLE
• abortifacient
• Psoriasis
• MOA: Inhibits DHFR -> no folate-> no DNA or RNA synthesis

• TOXIC: Nephrotoxic
• Myelotoxic (dose-limiting)
• Pulmonary & liver toxicities
• GIT (mucositis)

• NORMAL CELL RESCUE: Leucovorin
• BM RESCUE: G-CSF-Filgrastim

Antidote: Folinic acid - displaces methotrexate and provides carbon for purine synthesis.

• USE: metastatic carcinoma of breast, GIT, esophagus.(with folinic acid = more stable. VS methotrexate)
• Carcinoma of the ovary, bladder, prostate, pancreas

MOA: inhibits thymidylate synthase -> DNA synthesis is blocked

• Toxicity: delayed: anorexia, N, alopecia, stomatitis, mucosal ulceration -> fulminant D-> shock and death.
• Myelosuppression
• Cardiotoxicity

• Resistance: Insufficient activation of 5-FU
• change in sensitivity of TS to the drug.

Inactivated by dihydropyrimidine. (def -> death)

• Alkylating agent (CCNS)
• Antimalignant

• USE: CLL
• solid tumors
• Non hodgkins lymphoma
• Ovarian carcinomas
• Neuroblastoma
• immunosuppressive to prevent graft rejection
• SLE

MOA: Prodrug transcription and translation interference.

oral or IV

• Metabolism: CYP450, CYP2B6 ->
• active phosphoramide mustard(nephrotoxic)
• Acrolein (hemorrhagic)

Given with high waterload -> alkaline urine prevents reabsorption

• TOXIC: myelosuppression
• permanent amenorrhea & azoospermia
• Leukemogenic
• cardiotoxic
• renal & bladder toxicity

Causes inappropriate secretion of ADH

• ANTIDOTE:
• Mesna - conjugates acrolein
• demeclocycline- blocks effect of ADH

• Resisitance: Inc DNA repair
• MDR overexpressed -> kicks out drug

Alkylating agent

Lipophilic & cross BBB

USE: malignant astrocytomas & metastatic tumors of the brain

TOXIC: CNS toxicity

MOA: disrupt transcription via reacting with guanine bases

• Cytotoxic (anthracycline) antibiotic
• IV : severe local vesicant action if extravasation occurs

• USE: Hodgkins Disease
• Non Hodgkins lymphoma
• osteosarcoma, Ewings Sarcoma

• MOA: prevents topoisomerase from resealing helical breaks
• free radical formation

• ANTIDOTE: Dimethyl sulphoxide - counteract free radical produced ulcers
• Dexrazoxane(iron chelator-> red cardiomyopathy)

• Toxicity: cardiomyopathy
• Myelosuppresion
• stomatitis
• (with azathioprine) cholestasis

RESISTANCE: abn transport in and inc MDR

pegylated liposomal doxorubicin -> AIDS- related Karposi's sarcoma

• Vinca alkaloid
• Antimalignant, antimitotic

neurotoxic

USE: Hodgkins diseases, peds leukemia

• S/E: peripheral nerve neuropathy
• sensory & motor paresthesias

RESISTANCE: inc MDR gene

• MOA: spindle poisons
• bind to tubulin and prevent assembly of microtubules
• M phase

• Vinca Alkaloid
• Antimalignant, antimitotic

• USE: Hodkins
• Testicular carcinoma

• MOA: spindle poisons
• bind to tubulin and prevent assembly of microtubules
• M phase

• S/E: Reversible myelosuppression
• leukopenia and alopecia

RESISANCE: inc MDR gene

Natural products

• USE: 1st & 2nd advanced ovarian cancer
• metastatic cnacers

Given with corticosteroid, antihistamine, and histamine H2 receptor antagonist -> prevent severe hypersenstivity reactions

MOA: inhibit microtubule disassembly -> microtubule accumulation

• TOXIC: Hypersensitivity
• Neutropenia
• Cardiac conduction defects
• Peripheral neuropathy

Selective estrogen receptor modulator

• USE: breast cancer tx and prophylaxis
• infertility
• gynecomastia
• older women with inoperable tumors

Long use -> inc risk of endometrial cancer

MOA: blocks estrogen binding

TOXIC: N/V, hot flashes, vaginal bleeding, hypercalcemia, ocular dysfunction, peripheral edema

Aromatase inhibitor

MOA: prevent estrogen synthesis

L- asparagine -> aspartic acid & ammonia -> apoptosis

• Toxicity: Hypersensitivity
• intracranial hemorrhage

Cisplatin

USE: Urinogenital, testicular, ovarian, and bladder cancer

MOA: Diffuses and Cl replace water -> inhibition of replication and transcription

• TOXIC: nephrotoxicity
• electrolyte disturbances
• otoxicity

ANTIDOTE: amifostine -> thiol metabolites which scavange free radicals

Aplastic Anemia

• Monoclonal AB
• anti CD 20

specific breast cancer HER2 amplification