Neoplasia

Doxorubicin (Adriamycin) side effects

*Cariotoxicity- monitor EKG Red orange urine 1-2 days is normal

Causes of cancer

Carcinogens Chemicals- tobacco, asbestos (lung cancer), benzene (leukemia) Physical- X-rays (leukemia), UV light from sun (skin cancer) Biological- viruses (HSV, Epstein Barr, papilloma virus, cytomegalovirus, HIV Oncogenes Damage to tumor suppressor gene

Antineoplastic drugs

Alkylating agents- form bonds with DNA, prevent cell division Antimetabolites- resemble building blocks of cells, disrupt metabolism of nucleic acid Anti-tumor antibiotics- antibiotics that can kill some cancer cells Natural products- from plants, prevent division of cancer cells Hormones and hormone agents- slow growth of hormone dependent tumors Biologic response modifiers and monoclonal antibodies- enhance body's ability to remove cancer cells

Tamoxifen

Estrogen receptor blocker Oral antiestrogen Approved for breast cancer prophylaxis in high risk pts and adjunctive therapy to decrease incidence in opposite breast High risk- defect to tumor suppressor gene

Toxicity of Antineoplastic Drugs

Alopecia- hair loss Mucositis- epithelial lining of digestive tract becomes inflamed results in ulcerations, difficulty eating or swallowing, GI bleeding, intestinal infections, severe diarrhea Stem cells in bone marrow may be destroyed- causes anemia, leukopenia, thrombocytopenia Nausea and vomiting Vesicants- agents that can cause tissue injury if they escape from artery or vein, can cause extravasation that leads to severe tissue and nerve damage, local infection loss of limb Long term- possible infertility, increased risk for secondary tumors

Drugs with high emetic potential are pretreated with

Antiemetics: Zofran Compazine Reglan Ativan

Methotrexate (Rheumatrex, Trexall)

Antimetabolite Agent and folic acid analog Mechanism of action- stops protein and folic acid synthesis which inhibits replication of rapidly dividing cells Cell cycle specific- S phase Also used in RA, SLE, psoriasis, UC

Doxorubicin (Adriamycin)

Antitumor antibiotics Mechanism of action- interfere with RNA and DNA synthesis, for solid tumors of bone Green tea may enhance anti-tumor activity

Doxorubicin (Adriamycin) administration

Avoid skin contact can cause pain and tissue damage Use cold pack if it gets on skin to decrease absorption

Chemotherapy Schedule

Balance toxic dose with well being

Bone marrow depression treated with

Bone marrow transplant Platelet infusion Growth factors

Cancer/carcinoma

Charatcerized by rapid uncontrolled cell division Cells lose normal functions and invade normal tissues Named for tissue where it originates Atypical

Cancer treatment goals

Cure Control (slow down) Palliation of symptoms (relieve pain) Prophylactic Reconstructive

Methotrexate (Rheumatrex, Trexall) contraindications

Don't take if pregnant Alcoholism CLD Immunosuppressed

Methotrexate (Rheumatrex, Trexall) black box warning

Fatal myelosupression- when combined with NSAIDs Hepatotoxicity Ulcerative stomatitis- ulcers and erosions in the mouth- oral care SJS

Tamoxifen administration

Give with foods or fluids

Adjuvant chemotherapy

Goals- cure, control, palliation (reduce violence, ease symptoms) Often combined with or done after surgery and radiation to increase chance of cure May be given as chemoprophylaxis to prevent cancer in high risk patients Example- tamoxifen to prevent recurrent breast cancer

Cyclophosphamide (Cytoxan) side effects

Hemorrhagic cystitis- test urine for blood Hydrate pt!!! Urinate every 1-2 hours

Hair follicles, bone marrow, GI tissue have

High growth factor This explains may adverse effects Example- hair loss

Leukemias and lymphomas have

High growth fraction= more effective chemotherapy

Chemotherapy Methods of Administration

IV- port in subclavian vein, most common because less harmful to veins Continuous infusion Oral IM Regional administration Subcutaneous Topical

Adverse effects of alkylating agents

Immunosuppressant effects Thrombocytopenia N/V Anorexia Diarrhea Alopecia Hemorrhagic cystitis- inflamed bladder May cause permanent sterility

Tamoxifen black box warning

Increased risk of uterine cancer- Pap smears Slight increase in thrombosis

Neutropenia

Less than 1500 cells/ml

Methotrexate (Rheumatrex, Trexall) antidote

Leucovorin (folic acid)

Vinocristine (Oncovin) antidote

Leucovorin (folic acid)

Solid tumors have

Low growth fraction= less sensitive to chemotherapy

High growth fraction =

Many replicating cells Antineoplastic drugs are much more toxic to tissues and tumors with high growth fractions and will have greater success rate

Growth Fraction

Measure of how manny cells are undergoing mitosis Ratio of replicating cells to the number of resting cells *Major factor in determining success of chemotherapy

Alklating agents

Mechanism of action- changing structure of DNA in cancer cells Use is limited because can cause significant bone marrow suppression

Factors that determine response in chemotherapy

Mitotic rate of tissue of origin- rapid mitotic rate= greater response Size of tumor- smaller tumor= greater response Age of tumor- younger tumor= greater response Location of tumor- few agents cross blood brain barrier Presence of resistant tumor cells- resistant malignant cells pass resistance to daughter cells

Antineoplastic therapy

More effective against cells that are replicating- percent of tumor cells dividing at time of chemo is critical Cancer cells often develop resistance to antineopastic drugs- multiple drugs from divergent antineoplastic classes are given to affect different stages of the cancer cell's life cycle and attack various clones within a tumor Lowers dosages of each individual drug this reducing toxicity

Vinocristine (Oncovin) administration

Must be given IV Avoid skin contact can cause pain and tissue damage Use heat if it gets on skin

Vinocristine (Oncovin) side effects

Neurotoxicity- neuro checks! Peripheral neuropathy Particular in children Ptosis- eyelid drooping

Cyclophosphamide (Cytoxan)

Nitrogen mustard alkylating agent Mechanism of action- attaches to DNA and disrupts replication Primary use- treat wide variety of cancers, also seen in organ transplants

Dosing schedules

Specific dosing protocols: -depend on type of tumor, stage of disease, overall condition of pt -may be given as a single dose or several doses -may be given within days or after several weeks Gives normal cells a chance to recover Sometimes optimal dose must be delayed: -let pt recover from drug toxicities -example is in bone marrow suppression

Methotrexate (Rheumatrex, Trexall) side effects

Stomatitis that may require suspension of treatment- may lead to hemorrhagic enteritis form intestinal perforation

Treatments for cancer

Surgery Radiation Anti neoplastic/chemo therapy Biological and targeted therapies Gene therapy Hormone therapy Hematopoietic stem cell transplantation

Cyclophosphamide (Cytoxan) administration

Take with meals or divide dose Monitor platelet count for IM admin- hold if low- avoid OTC drugs with aspirin If taking PO give in AM because of infrequent urination at night increasing risk of cystitis

Nadir of antineoplastic drugs

The lowest point to which erythrocyte, neutrophil, platelet count is depressed by the drug

Chemotherapy effectiveness

The result of its ability to: Interfere with/alter a critical step in the cell cycle (cell cycle specific) Affect normal patterns of metabolism which ensure continuity of cell function (cell cycle non specific)

Chemoprophylaxis

Uncommon because of serious adverse effects

Vinocristine (Oncovin)

Vinca alkaloid, mitotic inhibitor, natural product Mechanism of action- prevents mitosis Cell cycle specific- M phase Minimal immunosuppression

Radiation therapy

With a radioactive substance, x-ray, or radiation Most successful and produces the fewest adverse effects for cancers that are localized Frequently prescribed post op to kill cancer cells that may remain following an operation

Methotrexate (Rheumatrex, Trexall) administration

Without food- food delays PO absorption >180mg/day caffeine may decrease effectiveness when taken for RA

Tamoxifen side effects

menstrual irregularities hot flashes bruising Fluid retention Vaginal discharge "Tumor flare"- idiosyncratic- increase in tumor size May increase calcium levels

Multiple-Drug Strategy

• Multiple drugs from different classes - Affect different stages in cell cycle - Use different mechanisms of action to increase cell kill • Combinations allow for lower doses - Reduce toxicity - Slow development of resistance

Achieving Total Cure

• Total cure = every malignant cell removed or killed - Even one cell could reproduce - Immune system eliminates very small number of cancer cells • Important to diagnose cancer early - Treat with surgery, radiation, chemotherapy