CHEMOTHERAPY

GENERAL PRINCIPLES

n   DNA Review

–   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

GENERAL PRINCIPLES

n   Cancer Cell Cycle

–   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

n   Drug Resistance

–   Innate

–   Acquired

GENERAL PRINCIPLES

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

NITROSOUREAS

n   Crosses Blood Brain Barrier

 

n   Effective against CNS tumors

CISPLATIN

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®)

DOXORUBICIN

n   Toxicities

–   Bone marrow aplasia

–   Delayed cardiotoxicity leading to CHF

n   Cannot exceed maximum cumulative lifetime dose

BLEOMYCIN

n   Used in combination

n   Toxicities

–   Pneumonitis

–   Minimal effect on bone marrow

METHOTREXATE

n   Interferes with activiation of folic acid to tetrahydrofolate

 

n   May require leucovorin rescue

HORMONAL THERAPY

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

ANTI-ESTROGENS

n   Palliative therapy of breast cancer

n   Prevention of breast cancer

n   Possible adverse reaction of uterine cancer

CORTICOSTEROIDS

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 ??

TOXICITY REVIEW

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)