CHEMOTHERAPY

– Double helix structure
– Chromosomes that direct cellular life
– Directs formation of RNA
– Protein synthesis dependent on mRNA and tRNA
– Each 3 codones make up an amino acid
– Chemotherapy can block synthesis

– S Phase is replicating phase
n Most drugs work on this phase
– G° Phase is non-replicating phase
n No drugs can work on this phase

Innate
– Acquired

n Drugs kill by first order kinetics
– Effective therapy kills 99.9% of tumor cells
n Importance of scheduling regimens
n Advantages of combination therapy

ALKYLATING AGENTS
n Causes Abnormal pairing of DNA strands
n Toxicities - Rapid growing normal tissues - hematopoetic (blood cells), GI, hair, gonads
n Bone marrow depression occurs slowly and recovers in 4 to 6 weeks

n Crosses Blood Brain Barrier

n Effective against CNS tumors

n Extremely Toxic
– Nephrotoxicity - must use fluids and diuretics to protect kidneys
– Extensive nausea/vomit
n Prevention includes
– marijuana derivative dronabinol (Marinol®)
– metoclopramide (Reglan®)
– 5HT-3 Antagonist - ondasetron (Zofran®), granisetron (Kytril®)

n Toxicities
– Bone marrow aplasia
– Delayed cardiotoxicity leading to CHF
n Cannot exceed maximum cumulative lifetime dose

Pneumonitis
– Minimal effect on bone marrow2

n Interferes with activiation of folic acid to tetrahydrofolate

n May require leucovorin rescue

n Palliative therapy - not curative
n First line therapy - less toxic
n Sex Hormone Therapy
– Estrogens - Tx of testosterone sensitive tumors
– Testosterone - Tx of estrogen sensitive tumors
– Progesterone - Tx of uterine cancers

n Palliative therapy of breast cancer
n Prevention of breast cancer
n Possible adverse reaction of uterine cancer

n Adjunct therapy
– lymphomas
– leukemias

VINCRISTINE
n Used in combination
n Toxicities
– Neurologic numbness and weakness
– Minimal effects on bone marrow

IMMUNOADJUVANT
n Levamisole
n BCG Vaccine
n Interferons
n Laetrile ??

n Nausea/vomiting
– Pretreat prior to therapy
n Alopecia
n Bone Marrow Depression
– Treat with filgrastim (Neupogen®)
n Extravasation of vesicant drugs
– Prevented with careful administration

MISCELLANEOUS
n COMBINATION THERAPY REGIMENS

n DOSE BY SURFACE AREA (mg/M²)