- rate of growth matched to cell death
- Growth fraction: measure of the number of cells undergoing mitosis in a tissue.
- Tumor cells escape signal to die and achieve immortality.
- don't contribute to function of a organ
- Proliferate despite lack of growth initiating signals.
- grows slowly
- rarely have necrosis
- function similar to host organ
- grow rapidly
- have necrotic areas
Success of chemotherapy
- Cure: free of cancer for a period of time
- Palliation: measurement of the patients quality of life.
- Antineoplastic: cell cycle specific
- cell cycle non-specific
- adjuvant chemotherapy: antineoplastics after surgery or radiation.
- myeloablation: complete destruction of hematopoietic bone marrow cells
Cancel cells and drug resistance?
- They're adaptive-mutate to resist drugs
- Cells can repair DNA damage from chemo
- Cell membrane prevent drugs from working.
- Gene amplification leading to overproduction of protein-making drug less effective.
- Number of cells undergoing mitosis in a tissue
- Dependent on location of cancerous cells. Some cells proliferate faster then others.
how to improve success of chemo?
- dosing schedules
- combination chemo
- route of admin: Po, IV, Intrathecal, intrarterial, intraperitoneal, intravesicular.
Cancer treatment SE?
- constipation or diarrhea
- hair loss
Toxic effects of antineoplastics and which systems are affected the most?
- hematologic: myelosuppression: bone marrow suppression-Nadir: lowest point of RBC and WBC/platelets.
- gastrointestinal: emetic potential, Mucositis, cachexia
- Cardiopulmonary: doxorubicin/bleomycin.
- urinary: may lead to renal failure
- Reproductive: infertility
Safe handling of chemotherapy drugs?
- Prevent skin absorption
- prevent inhalation by wearing masks
- appropriate management of pt.s bodily fluids.
Major classification of antineoplastics?
Need to know for exam
- alkylating agents: cyclophosphamide (Cytoxan)
- antimetabolites: methotrexate (Rheumatrex)
- antitumor antibiotics: doxorubicin (adriamycin)
- Hormones: tamoxifen
- plant alkaloids: vincristine (Oncovin)
- biologic response modifiers and monoclonal antibodies.
- Alters the shape of DNA double helix
- prevent DNA from duplicating
- kills cancer cells when they divide
- strong vessicant
- secondary malignancy: increased risk of causing other cancer.
- broad spectrum: lymphomas, myelomas, leukemias, pancreatic, testicular, ovarian, breast.
- Therapeutic class: alkylating agent
- Preg cat: D
- MOA: Cell cycle non specific- causes cross linking of DNA strands-prevents cell division.
- Indications: Cancers...
- Contraindications: Many, but mainly hepatic impairment or other impairments of your body that this drug will effect.
- Adverse effects: alopecia, disorder of ksin pigmentation, N/V, cardiotoxicity, CHF, many...
- Alert: Void frequently to prevent bladder irritation.
Antimetabolites Adverse effects?
- fatal bone marrow toxicity at high dose
- hemorrhage, nausea, vomiting, anorexia, GI ulcerations, intestinal bleeding.
- Contraindicated in pregnancy, hepatic, cardiac, renal insufficiency, myelosuppression and blood dyscrasia.
- Avoid preg. for 6 months after therapy.
- Therapeutic class: antimetabolite
- Preg cat: x
- MOA: blocks synthesis of folic acid Vitamin B)=powerful immunosuppressive.
- Indications: Used for cancers and diseases that have an over-reactive immune system.
- Contraindications: hepatic impairment, blood dyscrasias, severe COPD
- Adverse: N/V, myelosuppression, pulmonary toxicity.
Most are cell-cycle non-specific
- bleomycin, adriamycin, actinomycin
- bind to DNA, preventing DNA-RNA synthesis
- Therapeutic class: Antitumor antibiotics
- Preg cat:
- MOA: Bind to DNA-preventing DNA-RNA synthesis. decreasing cell replication.
- Indications: acute lymphoid leukemia, AML, Aids related kaposi, breast cancer.....antineoplastic...many cancers.
- contraindications: hepatic impairment, myelosuppression, MI-insufficiency.
- adverse: Turns urine/tears red, temporary infertility, secondary malignancy, N/V, rash, mucositis, excessive lacrimation, cardiotoxic.
- Alerts: neutropenic precaution, monitor cardiac function-3lead, observe s/s hepatic dysfunction, very good oral hygiene.
- Cell-cycle specific
- Vincristine: derivative of periwinkle plant-vinca alkaloids.
- MOA: blocks formation of mitotic spindle during mitosis( prevents cell division)
- Indications: hodgkin/ non-hodgkin lymphomas, leukemia, kaposi sarcoma, wilms tumor(found on kidneys-young children), bladder carcinoma, breast carcinoma.
- Contraindications: charcot-marie-tooth syndrome. Intrathecal use
- Alert: Very toxic and therapeutic doses have serious side effects.
- Adverse: Neurotoxic: paraesthesia/neuropathies-major dose limiting effect.
- N/V, Stomatitis, abdominal pain, vesicant.
Hormones and hormone antagonists
- treat hormone sensitive tumors
- Block substanes neccessary for tumor growth
- gonadal hormones
- estrogen hormones
- androgen hormones
Antiestrogen to prevent tumor growth.
- therapeutic class: estrogen receptor blocker
- MOA: blocks estrogen receptor on the breast, but activates estrogen receptors elsewhere. increases mineral density of bone and lowers LDL levels.
- Indications: Breast cancers that require estrogen to grow.
- Contraindications: concomitant use of anticoagulant therapy. increases risk of ductal carcinoma. DVT, PE.
- Adverse: hot flashes, fluid retention, increases rates of endometrial cancer.
- Also approved for prophylaxis of breast cancer....
Biologic response modifiers (BRM)
- Stimulates bodys immune system to kill tumor cells.
- BRM: Immunostimulant (interferon, interleukins).
- some dampen immune system (monoclonal antibodies)
- Interferon: natural protein produced by T-cells in response to a viral infection.
- interferon alfa 2-A and 2-B used to treat hepatitis B and C, kaposi sarcoma, hairy cell leukemia, chronic myelogenous leukemia
- Interleukin 2: activates cytotoxic lymphocytes and promotes action of the immune response. adesleukin is an example.
Monoclonal antibodies (MAB)
- molecularly targeted agents
- require that the tumor cells have specific protein receptors.
- Binds to CD20 cell surface antigen of B-lymphocytes.
- Adverse: myelosuppression, pancytopenia, tumor lysis syndrome(ARF), hypotension, night sweats, joint and muscle aches.
Reducing SE of chemo?
colony stimulating factors as well
- Antiemetics (zofran)
- RBC stimulates: Epotein/epogen
- neutrophil stimulates: neupogen
- platelet stimulates: neumega
- Laxatives and stool softeners.
- Granulocyte-macrophage colony stim factor-increases production of macrophages.
Know these prototype drugs....
- cyclophosphamide, (Cytoxan)
- doxorubicin (Adriamycin)
- methotrexate (Rheumatrex)
- vincristine (oncovin)
Cell cycle non specific chemo drugs? what do they do? how do they work?
Are able to kill a cell during any phase of cell cycle replication. these are usually given in a bolus over 20 mins.
Cell cycle specific chemo drugs? what do they do? how do they work?
are only able to kill a cell during a specific phase, not during the resting phase. These are usually given in divided doses to increase efficacy