CANCER CHEMOTHERAPY

Rets Y. Jacot, M.D. Jacot,

Chemotherapy

Cancer Chemotherapyy

Difficult to administerNon-selective Toxicity

y

Length of time given is subjected to studies Tumor resistance can develop against a drug

y

Basic Concepts in Chemotherapyy

Destroy cancer cells by interfering with their reproduction Act at specific points in the cell cycle Affect any rapidly dividing cell within the body, thus having the potential for toxicity development in healthy, functional tissue (bone marrow, hair follicles, GI mucosa) To reduce possibility of toxicity and drug resistance, combination therapy is often used Available in oral, parenteral and topical preparations

y y

y

y

ChemotherapyInduction chemotherapy y Adjuvant chemotherapy y Neoadjuvant chemotherapyy

Types of chemotherapyy y

Adjuvant micrometastases Neoadjuvant shrinks a tumor prior surgical removal Primary therapy treats a localized tumor when theres an alternative, less effective Induction treats a cancer for which there is no alternative treatment Combination enhances or synergizes the therapeutic actions of other cytotoxic drugs Prophylactic to prevent micrometastases

y

y

y

y

Primary Chemotherapyy

Neoplasms in w/c CTX is the primary therapeutic modality for localized tumors - Large cell lymphoma - Lymphoblastic lymphoma - Hodgkins disease - Wilms tumor - Embryonal rhabdomyosarcoma - Small cell lung cancer - CNS lymphomas

Neoadjuvant Chemotherapyy

Neoplasms in w/c primary CTX can allow less mutilating surgery - Anal carcinoma - Bladder carcinoma - Breast cancer - Esophageal cancer - Laryngeal cancer - Osteogenic sarcoma - Soft tissue sarcoma

General GroupsCell cycle Nonspecific Act on all phases Alkylating drugs Antitumor antibiotics Nitrosoureas Steroid hormones

Cell cycle specific

Act on specific phase of mitosis Antimetabolites (Effective at S phase) Vinca Alkaloids (effective at M phase) Topoisomerase I Inhibitors (S phase) Antitumor antibiotics

Phases of Cell Cycle

Combination Chemotherapyy

CCS and CCNS drugs are usually combinedDecreases drug resistance Intensifies therapeutic effect Reduces drug toxicity (lower doses)

y

Examples:CMF (cyclophosphamide, methotrexate, 5-FU) for breast cancer MOPP(mechlorethamine, vincristine,procarbazine, prednisone) and ABVD(Adriamycin, bleomycin, vinblastine, dacarbazine) in Hodgkins lymphoma

General side effectsy

Attack rapidly dividing cellsBlood (neutropenia and thrombocytopenia) Hair Mucous membranes of GI tract (nausea and vomiting)

y

Common nursing interventionsMonitor CBC Give anti-emetics Soft toothbrush Asepsis/ infection prevention Proper hydration

PrePre-chemo considerationsDiscuss with client the drug, length of time, side effects y Emphasize importance of adequate fluids y Watch out for extravasation of IV drugs y Record client and family responsesy

Basic Conceptsy

Pattern of neutropenia after chemotherapyMinimal neutropenia 4-7 days after treatment Nadir (period of maximum neutropenia) 8 to 12 days after treatment Return of normal number of neutrophils 14 to 18 days after treatment

Alkylating Drugs (CCNS)Kill cells by altering DNA structure by forming cross-linkages with DNA strands y Effective in leukemia, lymphoma, solid tumors y Include:y

Nitrogen mustards Nitrosoureas Alkyl sulfonates Alkylating-Like Drugs

Alkylating Drugs (CCNS)y

Common side effects:BM suppression Nausea/vomiting Stomatitis Alopecia Gonadal suppression Renal toxicity

Alkylating DrugsSubgroup Nitrogen Mustards Drug Cyclophosphamide, Ifosfamide Chlorambucil Carmustine Lomustine Busulfan Altretamine Properties Causes hemorrhagic cystitis

Nitrosoureas

May be used for brain tumors For treating AML, CML Primarily for ovarian CA; can cause peripheral neuropathy Renal toxicity

Alkyl Sulfonates Alkylating-Like

Platinum compounds

Cisplatin Carboplatin

Antimetabolites (CCS)Oldest group of anti-cancer drugs Resemble natural metabolites and disrupt metabolic processes y Cell cycle specific inhibition of S-phase y Folic acid analog - Blocks the action of the enzyme dihydrofolatey y

reductase which inhibits production of coenzyme needed for synthesis of thymidylic acid precursor for nucleic acid replicationRNA

y

Pyrimidine & purine analogs - block enzymes needed during the synthesis of DNA &

Antimetabolitesy

Methotrexate (FA antagonist)Treats solid tumors, sarcomas, choriocarcinoma Should keep client hydrated

y

5-Fluorouracil (Pyrimidine analog)Prevents thymidine production Watch out for thrombocytopenia and anemia

Antimetabolites (contd)y

5-mercaptopurine (Purine analog)First used for treating ALL Also used as an immunosuppressive drug May be hepatotoxic

y

Hydroxyurea (Ribonucleotide reductase inhibitor)For melanoma, CML, and ovarian cancer Long duration of action

y

Pentostatin (Enzyme inhibitor)For treating hairy cell leukemia not responsive to alpha interferon

AntiAnti-tumor antibiotics-

Cell cycle specific; inhibit RNA & protein synthesis or rapidly dividing cells Produced by the bacterial species Streptomyces Dactinomycin, Daunorubicin, Doxorubicin, & Plicamycin - use complex mechanisms to combine w/ DNA base pairs, thus interfering w/ DNA, RNA, & protein synthesis

y y

AntiAnti-tumor antibioticsy

Inhibit protein and RNA synthesis and bind DNA, thus causing fragmentation BleomycinTreating squamous cell CA and lymphomas Low incidence of bone marrow suppression, but prone to anaphylaxis

y

y y

DoxorubicinSeverely cardiotoxic (monitor ECG)

PlicamycinCauses hemorrhage, nosebleeds

Miscellaneous Drugy

AnastrazoleTreat advanced breast CA in post-menopausal women Given only orally Can cause diarrhea, headache, hypertension

y

CisplatinPlatinum based chemotherapy drug Nephrotoxic and neurotoxic

Mitotic inhibitors (CCS)y

Vinca alkaloidsDerived from periwinkle plant

y

Antimicrotubules (Paclitaxel)From the bark of the yew tree

y

Topoisomerase derivativesSemisynthetic products of podophyllotoxin (comes from mandrake plant)

Mitotic inhibitors (CCS)y

Natural or semisynthetic products derived from different plants Etoposide - semisynthetic derivative of podophyllotoxin, derived from root of May-apple plant - affect G2 phase pf cell cycle - causes cell lysis at high dose - prevents cells from entering mitosis stage & inhibit DNA synthesis

y

Mitotic inhibitors (CCS)y

Vinca alkaloidsVinblastine cause severe bone marrow depression Vincristine cause CNS effects and peripheral neuropathy

y

PaclitaxelFor treating ovarian and breast cancer Long duration of action

y

Irinotecan (Topoisomerase I)Severe diarrhea and extreme immunosuppression

y

Etoposide (Topoisomerase II)Monitor BP closely as it can cause hypotension

Hormones and hormone antagonistsy

ProgesteronePalliative treatment of endometrial and breast cancer

y

Hormonal antagonistsAminoglutethimidex for adrenal carcinoma

Megestrolx Palliative treatment of advanced breast CA and endometrial CA; may promote weight gain

Tamoxifenx Palliative treatment for advanced breast CA x Competes with estrogen receptors

Enzymey

L-AsparaginaseFor ALL Used in combination with other drugs

Latest trends in chemotherapyy

Monoclonal antibodiesRituximabx x x x For treatment of lymphoma and leukemias Mode of action: depletes B cells tag and destroy lymphoma cells Can also be used for autoimmune disorders such as rheumatoid arthritis

AntiAnti-angiogenesis drugy

Interferon alphaStimulate macrophages and NK cells Can bind to opioid receptors

y

ThalidomideInitially used as sedative Withdrawn from market in 1960s due to birth defects Re-approved in 2006 for use in multiple myeloma

Chemoprotectivey

Used as adjunct with other chemotherapeutic agents MesnaAdjuvant to cyclophosphamide to reduce risk for hemorrhagic cystitis Neutralizes acrolein (urotoxic metabolite)

y

y

AmifostineUsed to reduce neutropenia induced by DNAbinding chemotherapeutic drugs Can decrease nephrotoxicity of cisplatin

Biologic Therapyy

Cancer treatment that produces antitumor effects primarily through the action of natural host defense mechanisms or the administration of natural mammalian substances

Biologic Therapyy

Stimulate immune defense mechanisms Cause the tumor to appear more foreign compared to normal tissues Immune cells secrete two major classes of soluble protein - Antibody - Cytokines

y

y

Antibodyy

Two pairs of different polypeptide chains (heavy & light chains) Two recognition sites capable of combining with the immunizing antigen Mediate cell destruction by phagocytosis Cytotoxic T Lymphocyte (CTL) Natural Killer cells (NK)

y

y

y

y

Cytokinesy

Produced by lymphocytes (lymphokines) or monocytes (monokines) acting as true hormones acting on other cells at a distance from the secreting cells InterferonsReduce tumor cell proliferation & strengthening immune response

y

y y

Tumor Necrosis Factor (TNF) Interleukins 1 - 18

Side effects of chemotherapeutic agentsx Bone marrow suppression x Decreased WBC count (immunosuppression) x Decreased platelet count (thrombocytopenia) x Decreased hemoglobin and hematocrit (anemia) x Gastrointestinal effects: anorexia, nausea, vomiting, and diarrhea

Side effects of chemotherapeutic agentsx Stomatitis (inflammation of the mouth) and mucositosis x Alopecia (hair loss) x Fatigue x Xerostomia (dry mouth) x Other side effects specific to chemotherapeutic agent

Immunosuppressionx Client education for immunosuppression x Risk for infection is high when WBC count is low x Avoid crowds, people with infections, and small children when WBC is low x Use meticulous personal hygiene to avoid infection

Immunosuppressionx Wash hands before and after eating, after toileting, and after contact with other people and pets x Consume a low-bacteria diet; avoid undercooked meat and raw fruits and vegetables x Be aware of signs and symptoms of infection and report them immediately to primary care provider

Nursing management of immunosuppressiony

Monitor laboratory values: CBC with differential, platelets, BUN, liver enzymes Assess for infection; monitor vital signs for early indication of infection: fever, tachycardia, and tachypnea

y

Nursing management of immunosuppressiony

WBC suppression, malnutrition and presence of disease increase the risk of infection Utilize neutropenic precautions (lowbacteria diet, no fresh plants or flowers in room, no pets, no visitors with infections) when WBC level falls below predetermined level (such as 2,000mm3)

y

Thrombocytopeniax Client education for thrombocytopenia x Monitor stools and urine for bleeding x For shaving, use electric razor only x Avoid contact sports and other activities that may cause trauma x If trauma does occur, apply ice to area and seek medical assistance

Thrombocytopeniax Avoid dental work or other invasive procedures x Inform all healthcare providers of chemotherapy and/or radiation treatments x Avoid aspirin and aspirin-containing products x Safety precautions for oral hygiene; use soft toothbrushes and do not floss

Nursing management of thrombocytopeniax There is a high risk for spontaneous hemorrhage when platelet count is