ANTI-NEOPLASTIC DRUGS Younas masih New life college of nursing Karachi chemotherapy 10/24/2014

Objectives By the end of this session the learners will be able to, Review the characteristics of normal and malignant cells. Explain characteristics of anti-neoplastic drugs. Classify anti-neoplastic drugs Discuss the nursing care of patients who are on anti-neoplastic drugs. Calculate the drug dosage for Anti-neoplastic drugs. chemotherapy 10/24/2014

Anti-neoplastic drugs Cancer It is a term used for diseases in which abnormal cells divide without control and are able to invade other tissues. Cancer cells can spread to other parts of the body through the blood and lymph systems, this process is called metastasis. Categories of cancer Categorized based on the functions/locations of the cells from which they originate: •Carcinoma : skin or in tissues that line or cover internal organs. E.g., Epithelial cells. 80-90% reported cancer cases are carcinomas. •Sarcoma : bone, cartilage, fat, muscle, blood vessels, or other connective or supportive tissue. •Leukemia : White blood cells and their precursor cells such as the bon marrow cells, causes large numbers of abnormal blood cells to be produced and enter the blood. •Lymphoma : cells of the immune system that affects lymphatic system. •Myeloma: B-cells that produce antibodies- spreads through lymphatic system. •Central nervous system cancers : cancers that begin in the tissues of the brain and spinal cord. chemotherapy 10/24/2014

Cancer Therapeutic Modalities There are traditionally (classical) following modalities for the treatment of the cancer Surgery: 1/3 of patients without metastasis respond to surgery and radiation Radiation: If diagnosed at an early stage, close to 50% cancer could be cured. Chemotherapy: 50% patients will undergo chemotherapy, to remove micro metastasis. However, chemotherapy is able to cure only about 10-15% of all cancer patients chemotherapy 10/24/2014

New types of cancer treatment Hormonal Treatments: These drugs are designed to prevent cancer cell growth by preventing the cells from receiving signals necessary for their continued growth and division. E.g., Breast cancer – tamoxifen after surgery and radiation Specific Inhibitors: Drugs targeting specific proteins and processes that are limited primarily to cancer cells or that are much more prevalent in cancer cells. Antibodies: The antibodies used in the treatment of cancer have been manufactured for use as drugs. E.g., Herceptin, avastin Biological Response Modifiers: The use of naturally occurring, normal proteins to stimulate the body's own defenses against cancer. E.g., Abciximab, rituxmab Vaccines: Stimulate the body's defenses against cancer. Vaccines usually contain proteins found on or produced by cancer cells. By administering these proteins, the treatment aims to increase the response of the body against the cancer cells. chemotherapy 10/24/2014

Chemotherapy or Anti-neoplastic drugs It is the drug that is used to eliminate the cancer cells without affecting normal tissues (the concept of differential sensitivity). or Chemotherapy is the use of drugs to inhibit or kill proliferating cancer cells , while leaving host cells unharmed, or at least recoverable. chemotherapy 10/24/2014

General Rules for the chemotherapy Adjuvant therapy: Additional cancer treatment given after the primary treatment to lower the risk that the cancer will come back. Adjuvant therapy may include chemotherapy, radiation therapy, hormone therapy, targeted therapy, or biological therapy. Neo adjuvant therapy: Treatment given as a first step to shrink a tumor before the main treatment, which is usually surgery, is given. Examples of neo adjuvant therapy include chemotherapy, radiation therapy, and hormone therapy. It is a type of induction therapy. chemotherapy 10/24/2014

Cancer cells These cells can be divided in to 2 categories Proliferating Based on the DNA changes in cells, proliferating cycle of tumor cells can be divided into 4 phases Pre-synthetic phase (Gap 1 phase or G1 phase). Cells chiefly make preparations for the synthesis of DNA. Synthetic phase (S phase). Cells are synthesizing their DNA. Post-synthetic phase (Gap 2 phase or G2 phase). DNA duplication has been finished and they are equally divided to the two of future sub-cells. Mitosis phase (M Phase). Each cell is divided into two sub cells. Some of these new cells enter the new proliferating cycle, the others become non-proliferating cell chemotherapy 10/24/2014

Non proliferating Non-proliferating cells include G0 phase cells (resting-phase cells), G0 phase cells have proliferation ability but do not divide temporally. When proliferating cells are suffered heavy casualties, G0 phase cells will get into proliferating cycle and become the reasons of tumor recurrence. G0 phase cells are usually not sensitive to antineoplastic drugs, which is the important obstacle to tumor chemotherapy. chemotherapy 10/24/2014

Classification of the antineoplastic drugs Alkylating agents, Antimetabolites, Natural products, Hormones and antagonists Miscellaneous agents. chemotherapy 10/24/2014

Mechanisms of Antineoplastic Drugs Most antineoplastic drugs act on the proliferating cycle of cell (1) Destruction of DNA or inhibition of DNA duplication e.g. alkylating agents, mitomycin C (2) Inhibition of nucleic acid (DNA and RNA synthesis e.g. 5-fluorouracil, 6-mercaptopurine, methotrexate, cytarabine, etc. (3). Interfering with the transcription to inhibit RNA Synthesis e.g. dactinomycin, dauoruicin, and doxorubicin chemotherapy 10/24/2014

Mechanisms of Antineoplastic Drugs (4) Inhibition of protein synthesis e.g. vinca alkaloids, epipodophylotoxins, and paclitaxel (5) Interfering with hormone balance e.g. adrenal corticosteroids, estrogens, tamoxifen etc. chemotherapy 10/24/2014

Types of the antineoplastic drugs (Ⅰ) Alkylating Agents Alkylating agents act via a reactive alkyl (RCH2-CH2 + -) group that reacts to form covalent bonds with nucleic acids. There follows either cross-linking of the two strands of DNA, preventing replication, or DNA breakage. All alkylating agents are phase-nonspecific. kill rapidly proliferating cells, also kill non proliferating cells Cyclophosphamide: Most widely used in clinical therapy for treatment of cancer at present. It has no antineoplastic action outside the body and must be activated in the liver chemotherapy 10/24/2014

(Ⅱ) Antimetabolites It acts mainly on the S phase cells. has a serious myelo suppression Example: 5 FU, Methotrexate chemotherapy 10/24/2014

(Ⅲ) Natural Products The major classes of natural products include Antibiotics( Antitumor antibiotics) Vinca alkaloids Biologic response modifiers Enzymes Epipodophyllotoxins Taxanes chemotherapy 10/24/2014

Antibiotic antineoplastic agents Antibiotic antineoplastic agents: Damage DNA in cycling and non cycling cells Example: Dactinomycin (actinomycin D) This drug binds no covalently to double-stranded DNA and inhibits DNA-directed RNA synthesis. Dactinomycin is a phase-nonspecific agent, but it is more active against G1 phase cells. chemotherapy 10/24/2014

Vinca (plant) alkaloids Vincristine and vinblastine are alkaloids derived from the periwinkle plant. interfere with the assembly of spindle proteins during mitosis.. Act in M phase to inhibit mitosis, blocking proliferating cells as they enter metaphase. Both can cause bone marrow suppression and neurotoxicity chemotherapy 10/24/2014

(Ⅳ) Hormones and antagonists Adrenocortical steroids to inhibit the growth of cancers of lymphoid tissue and blood. Estrogen antagonists ( tamoxifen ) is indicated for breast cancer. Estrogen is used for prostatic cancer chemotherapy 10/24/2014

(Ⅴ) Miscellaneous agents Hydroxyurea inhibits ribonucleotidereductase. inhibition of DNA synthesis. It is specific for the cells of S phase The major adverse effect of this drug is bone marrow depression. chemotherapy 10/24/2014

Principles of combination therapies 1. Select drugs according to their phase specific characteristics 2. Combinations of antineoplastic drugs with different action mechanism 3. Combinations of antineoplastic drugs with other therapies 4. Select drugs according to antineoplastic range (spectrum) 5. Use right dose chemotherapy 10/24/2014

LIMITATIONS OF CYTOTOXIC AGENTS There are a number of problems with the safety profile and efficacy of chemotherapeutic agents These affect rapidly dividing cells so do not specifically target cancer cells in the resting phase. They also only influence a cell’s ability to divide and have little effect on other aspects of tumor progression such as tissue invasion, metastases or progressive loss of differentiation. cytotoxic are associated with a high incidence of adverse effects chemotherapy 10/24/2014

Side effects The most notable examples include Bone marrow suppression, Alopecia, Mucositis, Nausea and vomiting. Skin color changes Body ache Dirreahea chemotherapy 10/24/2014

Nursing care of the patients with chemotherapy Induction chemotherapy: chemotherapy given to induce a remission. Consolidation chemotherapy: chemotherapy given once a remission is achieved to sustain a remission. Maintenance chemotherapy: chemotherapy given after an initial chemotherapy course to prolong a response. Palliative chemotherapy: chemotherapy that is given specifically to address symptom management. First line chemotherapy: chemotherapy first used for treating cancer that has metastasized. Second line chemotherapy: chemotherapy given when a disease has recurred or the patient no longer responds to first line chemotherapy. Third and fourth line chemotherapy: chemotherapy given when a disease has recurred or the patient no longer responds to second and third line chemotherapy chemotherapy 10/24/2014

Nursing care of the patients with chemotherapy Following are the nursing management and care of the patient who is receiving chemotherapy Pre chemotherapy teaching of the patient , that includes (1). Teaching of side effects (2). Prevention (3). Diet (4). Regimen and cycles of the chemotherapy Decrease the level of anxiety of the patient chemotherapy 10/24/2014

Nursing care of the patients with chemotherapy Proper I/V cannulation (1). Proper site and side selection (mastectomy). (2). Proper vein selection Hydration teachings and checking of the patients (1). Pre hydration (2). Post hydration (3). Urinary output Keep patient under observation Check for I/V flow chemotherapy 10/24/2014

Nursing care of the patients with chemotherapy Check for signs of extravasations Check for hemorrhage and bleeding Check CBC ( RBC, WBC, Plt), Preventions (gum bleeding, urinary retention, proper diet and fluid intake ) Nausea and vomiting reducing strategies Teachings to increase the dietary intake chemotherapy 10/24/2014

Extravasations Extravasations has been termed “a dreaded complication of chemotherapy. Left untreated, vesicant chemotherapy extravasations have the potential to cause tissue necrosis, functional impairment, and permanent disfigurement. Surgical intervention and wound care often are required chemotherapy 10/24/2014

Extravasations chemotherapy 10/24/2014

Extravasations Management of the patients with extravasations Ask patient and other staff to keep on eye on the area which is cannulated for chemotherapy If signs of extravasations occurs immediately stop the medicine common symptoms of vesicant extravasations are redness and swelling and discomfort may or may not be present,10 application of a transparent dressing secures the IV device A blood return from the IV device should be obtained before administering a vesicant chemotherapy 10/24/2014

Extravasations 6. Apply topical heat or cooling (Local cooling using ice packs or cold gel packs whereas, Local warming (dry heat) is indicated for non-DNA-binding vesicant extravasation). 7. Antidotes and treatments (Local injection of sodium thiosulfate is the recommended antidote, Local injection of hyaluronidase) 8. Document the event 9. Inform the supervisor or manager about the event and explain to the patient and family 10. Monitor the site for further complications 11. Don’t use the area for chemotherapy chemotherapy 10/24/2014

References Cancer Chemotherapy. (2010, December 31). Retrieved from http://www.uic.edu/classes/pcol/pcol331/Antineoplastic%20Agents%202011%20Dental%20MARCH-1.pdf Kishore", W. (2011, March 23). Pharmacology of Antineoplastic Agents. Retrieved from http://pharmacology.xjtu.edu.cn/ppt/Anticancer.pdf Schulmeister, L. (2010). Preventing and Managing Vesicant Chemotherapy Extravasations. THE JOURNAL OF SUPPORTIVE ONCOLOGY, 8(5), 212-215. chemotherapy 10/24/2014