MEDICAL SURGICAL NURING

PRESENTED BYMRS HEENA MEHTAS.Y.M.SC NURSING

IVALUATION BYMR.P.YONATANSIR

ASSOCIATE PROFESSERJ G NURSING COLLEGE

CHEMOTHERAPY AND

RADITHERAPY

CHEMOTHERAPY

• INTRODUCTION OF CHEMOTHERAPY

• The use of chemicals to treat cancer

first began in the early 1940.The modern chemotherapy begun in 1948 with introduction of nitrogen mustard. Since that time Scientiests continued to search for medication to treat neoplasm.

• , such as a virus or other microorganism.

• DEFINITION OF CHEMOTHERAPY•  The treatment of cancer using specif

ic chemical agents ordrugs that are selec

tively destructive to malignant cells andtissues.

•  The treatment of disease using chemical agents or drugsthat are selectively 

toxic to the causative agent of thedisease, such as a virus or other microorganism.

OBLECTIVES OF THECHEMOTHERAPY• *The main objective in treating patients

with chemotherapy is• to maximize the death of malignant

tumor cells.• * To cure the client with cancer.• * To control the tumor growth when cure

is not possible.• *To extend the lifespan and improve the

quality of life of client with cancer.

HOW CHEMOTHERAPY WORKS• it is helpful to understand the

normal life cycle of a cell, or the cell cycle.• All living tissue is made up of

cells. Cells grow and reproduce to replace cells lost through injury or normal “wear and tear.”

• The cell cycle is a series of steps that both normal cells and cancer cells go through in order to form new cells.

• This discussion is somewhat technical, but it can help you understand how doctors predict which drugs are likely to work well together and how doctors decide how often doses of each drug should be given

• The cell cycle has 5 phases which are labeled below using letters and numbers. Since cell reproduction happens over and over, the cell cycle is shown as a circle. All the steps lead back to the resting phase (G0), which is the starting point.

• After a cell reproduces, the 2 new cells are identical. Each of the 2 cells made from the first cell can go through this cell cycle again when new cells are needed.

• The Cell Cycle• G0 phase (resting stage): The cell

has not yet started to divide. Cells spend much of their lives in this phase. Depending on the type of cell, G0 can last from a few hours to a few years. When the cell gets a signal to reproduce, it moves into the G1 phase.

• G1 phase: During this phase, the cell starts making more proteins and growing larger, so the new cells will be of normal size. This phase lasts about 18 to 30 hours.

• S phase: In the S phase, the chromosomes containing the genetic code (DNA) are copied so that both of the new cells formed will have matching strands of DNA. The S phase lasts about 18 to 20 hours.• G2 phase: In the G2 phase, the

cell checks the DNA and gets ready to start splitting into 2 cells. This phase lasts from 2 to 10 hours

• M phase (mitosis): In this phase, which lasts only 30 to 60 minutes, the cell actually splits into 2 new cells.• This cell cycle is important

because many chemotherapy drugs work only on cells that are actively reproducing (not cells that are in the resting phase, G0). Some drugs specifically attack cells in a particular phase of the cell cycle (the M or S phases, for example.

CHEMOTHERAPY DRUGS

•Chemotherapy drugs act through a variety of mechanism but, essentially, kill cells by:• Limiting DNA synthesis and expression- By interfering with synthesis of buiding blocks for nucleic acid.

•Cross- linking polymer DNA-Damaging the DNA template and cross-link the twostands of the double helix , preventing replication.

• DNA double stand breaks- Bind selectively with DNA, producing complexes that block DNA replication andformation of DNA dependent RNA.• Preventing formation of mitotic apparatus- Prevent chromosome segregation at mitosisby producing metaphase arrest.

CLASSIFICATION OF CHEMOTHERAAPY

• Chemotherapeutics agents are broadly classified as:• Cell cycle-specific Drugs: Those

chemotherapeutic agents that destroy cells in specific phases of the cell cycle . Most affect cells in the S-phase by interfering with DNA and RNA synthesis.

• Cell cyle non specific Drugs:• Those chemotherapeutic agents that act independently of the cell cycle phase are termed cell cycle non- specific drugs. These drugs usually have a prolonged effect on cell , leading to cellular damage or death. • ;

•Chemotherapeutic agents also classifiedaccording tovarious chemical groups eachwith a different mechanism of action. These include

1-Alkylating agents-• Alkylating agents are so named

because of their ability to alkylate many nucleophilic functional groups under conditions present in cells. They impair cell function by forming covalent bonds with the amino, carboxyl, sulfhydryl, and phosphate groups in biologically important molecules.

• Cisplatin and carboplatin, as well as oxaliplatin, is alkylating agents.

Polyfunctional Alkylating Drugs: Mechanism of Action

• Alkyl group transfer–Major interaction: Alkylation of DNA•Primary DNA alkylation site: N7 position of guanine

• interaction may involve single strands or both strands .

–Other interactions: these drugs react with carboxyl, sulfhydryl, amino, hydroxyl, and phosphate groups of other cellular constituents–These drugs usually form a reactive intermediate – ethylene ammonium ion.

• Polyfunctional Alkylating Drug Resistance

-Increased ability to repair DNA defects

-Decreased cellular permeability to the drug

-Increased glutathione synthesis

• Injection site damage (vesicant effects) and systemic toxicity.

• Toxicity:–dose related–primarily affecting rapidly dividing cells•  bone marrow•  GI tract–nausea and vomiting within less than an hour-- with mechlorethamine, carmustine (BCNU) or cyclophosphamide

–Emetic effects: CNS»reduced by pre-treatment with phenothiazines or cannabinoids.

•gonads

–Major Toxicity: bone marrow suppression• dose-related suppression of myelopoiesis:

primary effects on–megakaryocytes–platelets–granulocytes

• Bone marrow suppression is worse when alkylating agents are combined with other myelosuppressive drugs and/or radiation (dose reduction required)

•Oral Route of Administration:cyclophosphamide (Cytoxan), melphalan (Alkeran), chlorambucil (Leukeran), busulfan (Myleran), lomustine (CCNU,CeeNU)

• Nitrosoureas:– not cross reactive ( with respect to tumor resistance) with other alkylating drugs.–Nonenzymatic by transformation required to activate compounds.–Highly lipid- soluble-- crosses the blood-brain barrier (BBB)

•useful in treating brain tumors–Act by cross-linking: DNA alkylation–More effective against cells in plateau phase than cells in exponential growth phase–Major route of elimination:urinary excretion–Steptozocin:•sugar-containing nitrosourea

Other Alkylating Drugs• Procarbazine (Matulane)–Methylhydrazine derivative–Active in Hodgkin's disease

(combination therapy)–Teratogenic, mutagenic, leukemogenic.–  Side effects:• nausea, vomiting, myelosuppression• hemolytic anemia• pulmonary effects

• Dacarbazine (DTIC)–Clinical use:•Melanoma•Hodgkin's disease•soft tissue sarcoma

–Synthetic drug; requires activation by liver microsomal system.

• Parenteral administration

– Side effects:• nausea, vomiting, myelosuppression

• Altretamine (Hexalen)– Clinical use:• alkylating agent-resistant: ovarian

carcinoma– Activated by biotransformation

(demethylation)–  Side effects:• nausea, vomiting, central and peripheral

nervous system neuropathies.• relatively mild myelosuppressive effects.

• Cisplatin (Platinol)–Clinical use:•Genitourinary cancers–testicular–ovarian–bladder

• In combination with bleomycin and vinblastine: curative treatment for nonseminomatous testicular cancer

Alkylating Agent Toxicity: Summary

• IV mechlorethamine, cyclophosphamide, carmustine: Nausea and Vomiting (common)

• Oral cyclophosphamide: Nausea and Vomiting (less frequently)

•  Most Important Toxic Effect:Bone marrow suppression, leukopenia, thrombocytopenia

–secondary to myelosuppression --•severe infection•septicemia

–hemorrhage• Cyclophosphamide

(Cytoxan):alopecia, hemorrhagic cystitis (may be avoided by adequate hydration)

2- Anti-metabolites – • Anti-metabolites masquerade as purines

((azathioprine, mercaptopurine)) or pyrimidines—which become the building blocks of DNA. They prevent these substances from becoming incorporated in to DNA during the "S" phase (of the cell cycle), stopping normal development and division. They also affect RNA synthesis. Due to their efficiency, these drugs are the most widely used cytostatics

-Tumor resistance to methotrexate:• decreased drug transport into the cell• altered dihydrofolate reductase enzyme -- lower affinity for methotrexate• decreased polyglutamate formation• quantitative increase in dihydrofolate reductase enzyme concentration in the cell (gene amplification, increased message)

–  Adverse effects:• Bone marrow suppression• Dermatologic• GI mucosa• Adverse effects reversed by leucovorin

(citrovorum factor)–Leucovorin "rescue" may be used in

cases of over dosage or in high-dose methotrexate protocols

– Other uses:• Treatment of rheumatoid arthritis• In combination with a prostaglandin:

induces abortion

• Purine Antagonists– 6-Thiopurines (Mercaptopurine [6-MP]; Thioguanine

[6-TG])– Mercaptopurine (Purinethol)• Mechanism of Action:Activation by hypoxanthine-

guanine phosphoribosyl transferase (HGPRT) to form 6-thioinosinic acid which inhibits enzymes involved in purine metabolism. (thioguanylic acid and 6-methylmercaptopurine ribotide (MMPR) also active)• Clinical Use:– childhood acute leukemia– the analog, azathioprine (Imuran)--

immunosuppressive agent.

– Thioguanine• purine nucleotide pathway enzyme-inhibitor– decreased intracellular concentration of

guanine nucleotides– inhibition of glycoprotein synthesis–Mechanism of Action: inhibits DNA/RNA

synthesis

• Clinical Use:–Synergistic with cytarabine in treating

adult acute leukemia.– Drug resistance• Decreased HGPRT activity• In acute leukemia -- increased alkaline

phosphatase, which dephosphorylates thiopurines nucleotides

– Adverse Effects:• Both mercaptopurine and thioguanine,

given orally, are excreted in the urine.–6-MP is converted to an inactive

metabolite, 6-thioruric acid, by xanthine oxidase .6-TG: requires deamination before metabolism by xanthine oxidase.– In cancer (hematologic) chemotherapy,

allopurinol is used to inhibit xanthine oxidase, to prevent hyperuricemia associated with tumor cell lysis {xanthine oxidase inhibition blocks purine degradation -- purines (more soluble) are excreted instead of uric acid (less soluble)}

use of allopurinol thus blocks acute gout and nephrotoxicity.

However, the combination of allopurinol and 6-mercaptopurine, because of xanthine oxidase inhibition, can lead to mercaptopurine toxicity; This interaction does not occur with 6-TG.

-Fludarabine phosphate•parenteral administration; renal excretion•dephosphorylated to active form:•Mechanism of Action:DNA synthesis inhibition•Clinical Use:–lymphoproliferative disease

•Adverse Effect:dose-limiting -- myelosuppression.

–Cladribine:  (Leustatin)• phosphorylated by deoxycytidine kinase–incorporated into DNA–Mechanism of Action: increased strand breaks (inhibition of repair mechanisms)

• Clinical Use:–Hairy cell leukemia

• Adverse Effects:–Transient severe myelosuppression; possibly associated with infection.

– Pentostatin:• irreversible inhibitor adenosine deaminase– results in toxic accumulation of

deoxyadenosine nucleotides (especially in lymphocytes)

• Adverse Effects:– immunosuppression (T cell mediated immunity)–myelosuppression– kidney function impairment–CNS toxicity– liver toxicity

• Pyrimidine Antagonists:– Flurouracil (5-FU), normally given by IV

administration (oral absorption erratic)

• Biotransformed to ribosyl- and deoxyribosyl- derivatives.–Mechanism of Action:

» One derivative, 5-fluoro-2'-deoxyuridine 5'-phosphate (FdUMP), inhibits thymidylate synthase and its cofactor,a tetrahydrofolate derivative, resulting in inhibition of thymidine nucleotide synthesis.

» Another derivative, 5-fluorouridine triphosphate is incorporated into RNA, interfering with RNA function.

» Cytotoxicity:effects on both RNA and DNA• Clinical Use: Systemically -- adenocarcinomas;

Topically: skin cancer• Floxuridine (FUDR): similar to 5-FU, used for hepatic

artery infusion.

•

• Major Toxicity: myelosuppression, mucositis

– Cytarabine (ara-C) IV administration• Mechanism of Action:S phase-specific antimetabolite

– Biotransformed to active forms: ara-CTP, competitive inhibitor of DNA polymerase.» Blocks DNA synthesis; no effect on RNA or protein synthesis

– cytarabine incorporated into RNA and DNA -- interfering with chain elongation

• Clearance: deamination (inactive form)• S phase specificity: highly schedule-dependent• Clinical Use: almost exclusively for acute myelogenous leukemia•  Adverse Effects:–nausea–alopecia–stomatitis– severe myelosuppression

–Azacitidine (IV administration):•Mechanism of Action: active derivatives inhibit orotidylate decarboxylase -- reducing pyrimidine nucleotide synthesis; azacitidine -- incorporated into DNA and RNA; inhibits DNA, RNA, and protein synthesis.• Investigational drug -- second-line agent in treatment of acute leukemia• Adverse Effect: myelosuppression.

3- Plant alkaloids and terpenoids .

• hese alkaloids are derived from plants and block cell division by preventing microtubule function. Microtubules are vital for cell division, and, without them, cell division cannot occur. The main examples are vinca alkaloids and taxanes.

• Vinblastine -- (Velban)– Mechanism of action: microtubule depolymerization• Mitotic arrest at metaphase; interferes with chromosome

segregation

– Clinical Use::• Systemic treatment of Hodgkin's disease• Lymphomas

– Adverse Effects:• nausea• vomiting• alopecia• bone marrow suppression

• Vincristine -- (Oncovin)– Mechanism of action: microtubule depolymerization• Mitotic arrest at metaphase; interferes with chromosome

segregation

– Clinical Use::• In combination with prednisone: induction of remission in

children with acute leukemia• useful in treating some other rapidly proliferating neoplasms

– Adverse Effects:• significant frequency of neurotoxic reactions• occasional: bone marrow depression

• Podophyllotoxins (etoposide {VP- 16}and teniposide {VM-26})– Etoposide and teniposide:

structurally similar–Mechanism of action: Block cell

cycle: in late S-G2 phase• inhibition of topoisomerase II -- DNA damage

–IV administration–Urinary excretion; some in bile

–Clinical Use:•  Etoposide  (VP-16,VePe-sid):–monocytic leukemia–testicular cancer–oat cell lung carcinoma

•  Teniposide (Vumon): lymphomas–  Adverse Effects:• nausea• vomiting• alopecia• significant hematopoietic toxicity and lymphoid toxicity

• Camptothecins (topotecan and irinotecan )–Mechanism of action: interfere with activity of

topoisomerase I (cuts and religates single stranded DNA. DNA is damaged

– Clinical Uses:• Topotecan: metastatic ovarian cancer --

including cisplatin-resistant forms (as effective as paclitaxel)•  Adverse Effects: Topotecan --–Primary»neutropenia»thrombocytopenia»anemia

–Other»nausea»nominee»alopecia

• Irinotecan:prodrug-metabolized active topoisomerase I inhibitor–Used in management of colon and rectal cancer,

including tumors not responding to 5-FU–Adverse Effects: Irinotecan --»Most common: diarrhea»also common: nausea, vomiting

• Dose limiting adverse effect: myelosuppression

• Taxanes (Paclitaxel (Taxol) and Docetaxel (Taxotere))–Paclitaxel (Taxol): derivative of the

Western Yew–Mitotic spindle inhibitor: enhances

tubulin polymerization–Clinical Uses:•Ovarian•Advanced breast cancer

– Dose-limiting Adverse Effects:•neutropenia•thrombocytopenia•peripheral neuropathy

–Docetaxel (Taxotere):Used in advanced breast cancer•Adverse Effects:bone marrow suppression

4- Topoisomerase inhibitors-• Topoisomerases are enzymes our

cells use to break the DNA bonds before copying and repair of breaks after copying. Topoisomerase inhibitors interfere with DNA repair causing the cancer cell to die because damaged DNA cannot be translated into proteins, such as transport and digestive proteins that each cell needs to breathe or eat.

• Topoisomerase inhibitors are cell cycle specific, that is, they only kill cells that are in a particular phase of cell division and generally do not have any effect on other cells. Examples of Topoisomerase inhibitors are Etoposide and Topotecan.

• Topoisomerase inhibitors are agents designed to interfere with the action of topoisomerase enzymes (topoisomerase I and II), which are enzymes that control the changes in DNA structureby catalyzing the breaking and rejoining of the phosphodiester backbone of DNA strands during the normal cell cycle.

• In recent years, topoisomerases have become popular targets for cancer chemotherapy treatments. It is thought that topoisomerase inhibitors block the ligation step of the cell cycle, generating single and double stranded breaks that harm the integrity of the genome. Introduction of these breaks subsequently lead to apoptosis and cell death.

• Classification• Topoisomerase inhibitors are often

divided according to which type of enzyme it inhibits.• Topoisomerase I inhibitors:

irinotecan, topotecan, camptothecin and lamellarin D all target type IB topoisomerases,

• Topoisomerase II inhibitors: etoposide (VP-16), teniposide, doxorubicin, daunorubicin, mitoxantrone, amsacrine, ellipticines, aurintricarboxylic acid, and HU-331, a quinolone synthesized from cannabidiol.

• Numerous plant derived natural phenols (ex. EGCG, genistein, quercetin, resveratrol) possess strong topoisomerase inhibitory properties affecting both types of enzymes. They may express function of phytoalexins - compounds produced by plants to combat vermin and pests.

• Use of topoisomerase inhibitors for antineoplastic treatments may lead to secondary neoplasms because of DNA damaging properties of the compounds. Also plant derived polyphenols shows signs of carcinogenity, especially in feuses and neonates who do not detoxify the compounds sufficiently.An association between high intake of tea (containing polyphenols) during pregnancy and elevated risk of childhood malignant central nervous system (CNS) tumours has been found.

5- Cytotoxic antibiotics-• It is bind directly toDNA , thusinhibite

the synthesis of DNA and interfering with transcpition of RNA.• actinomycin ,anthracyclines,

doxorubicin• Daunorubicin,valrubicin ,epirubicin

are example of antibiotics.

Anticancer Drugs: Antibiotics

• Clinically useful anticancer antibiotics: derived from Streptomyces

• These antibiotics act by:– DNA intercalation, blocking synthesis of DNA

and RNA

• Anthracyclines: Doxorubicin (Adriamycin, Rubex, Doxil) and Daunorubicin (DaunoXome)– IV administration; hepatic metabolism; biliary

excretion; some urinary excretion; enterohepatic recirculation.

• Among the most useful anticancer antibiotics–Mechanism of action:• DNA intercalation -- blocking synthesis of

DNA and RNA; DNA strands scission -- by affecting topoisomerase II• Altering membrane fluidity and ion

transport• Semiquinone free radical an oxygen radical

generation (may be responsible for myocardial damage)

– Doxorubicin (Adriamycin, Rubex, Doxil)-- very important anticancer agent --

• Carcinomas-Doxorubicin•  breast carcinoma•  ovarian carcinoma•  thyroid carcinoma•  endometrial carcinoma•  testicular carcinoma•  lung carcinoma • Sarcomas-Doxorubicin•  Ewing's sarcoma•  osteosarcoma•  rhabdomyosarcomas•  

• Hematologic Cancers-Doxorubicin• acute leukemia• multiple myeloma• Hodgkin's disease• non-Hodgkin's lymphoma• Adjuvant therapy in: osteogenic sarcoma and breast

cancer• Generally used in combination protocols with:– cyclophosphamide (Cytoxan)– cisplatin (Platinol)– nitrosoureas

• Major Use: Acute Leukemia• Daunorubicin: limited utility-- limited efficacy in

treating solid tumors.• Idarubicin: approved for acute myeloid leukemia– Idarubicin in combination with cytarabine: more active

than daunorubicin in inducing complete remission in acute myelogenous leukemia.

• Adverse Effects:– Bone marrow depression (short duration)– Cumulative, dose-related, possibly irreversible

cardiotoxicity.– Total, severe alopecia

• Dactinomycin (Cosmegen)– IV administration; 50 percent remains

unmetabolized.–Mechanism of action: intercalation between

guanine-cytosine base pairs• inhibits DNA-dependent RNA synthesis• blocks protein synthesis

– Clinical Uses:• dactinomycin in combination with

vincristine (Oncovin)and surgery (may include radiotherapy) in treatment of Wilms' tumor• dactinomycin with methotrexate: maybe

curative for localized or disseminated gestational choriocarcinoma.

 Adverse Effects: Major dose limiting toxicity: bone marrow suppression (all blood elements affected -- particularly platelets and leukocytes)

occasional severe thrombocytopenianauseavomitingdiarrheaoral ulcersDactinomycin: immunosuppressive (patient should not receive live virus vaccines)alopecia/skin abnormalitiesinteraction with radiation ("radiation recall")

• Plicamycin (Mithramycin)• Mechanism of action:binds to DNA --

interrupts DNA-directed RNA synthesis–Also decreases plasma calcium

(independent tumor cell action;acts on osteoclasts)

• Clinical Uses:–some efficacy in testicular cancer that is

unresponsive to standard treatment:–especially useful in managing severe

hypercalcemia associated with cancer

•  Adverse Effects:–nausea–vomiting–thrombocytopenia–leukopenia–hypocalcemia–liver toxicity–bleeding disorders

• Mitomycin: (Mutamycin)–Mechanism of action:•metabolic activation to produce a DNA

alkylating agent.• Solid tumor hypoxic stem cells may be more

sensitive to the action of mitomycin.• Best available drug, in combination with x-rays,

to kill hypoxic tumor cells.– Clinical Use:• in combination chemotherapy {with vincristine

and bleomycin}: squamous sell carcinoma of the cervix

• adenocarcinoma of the stomach, pancreas, and lung {along with flurouracil and doxorubicin}• second-line drug: metastatic colon cancer• topical intravesical treatment of small bladder

papillomas.– Adverse Effects:• severe myelosuppression, especially after repeated

doses, suggest action on hematopoietic stem cells.• Vomiting• anorexia• occasional nephrotoxicity• occasional interstitial pneumonitis

• Bleomycin (Blenoxane)• Mechanism of Action:binds to DNA --

produces single- and double-strand breaks (free radical formation)– Cell cycle specific: arrests division in G2– Synergistic effects with vinblastine and

cisplatin (curative protocol for testicular cancer)

• Clinical Uses:– Testicular cancer– Squamous cell carcinoma: head, neck, cervix,

skin, penis, and rectum

–combination treatment: lymphoma– intracavity treatment: malignant effusions

in ovarian breast cancer• Adverse Effects:–Anaphylactoid reaction (potentially fatal)–Fever–anorexia, blistering, hyperkeratosis (palms)–pulmonary fibrosis (uncommon)

• No significant myelosuppression

6-Nitrosourceas-

•It is like alkylating agents,break DNA helix.

• Structural Features• Nitrosourea• Mechanism of Action• Hydrolysis of Nitrosourea group produces two

active species• Alkylating Agents with Nitro group provides

crosslinking in DNA for Chemotherapy• Carbamoylating agent O=C=N-R causing toxic

effects of blocking DNA Polymerase and DNA Repair enzymes by binding to nucleophilic sites on proteins

• Toxicity• Carbamoylating agent • Carcinogenic• Mutanogenic• Infertility• Bone marrow depression

Agent Structure Details

Lomustine

Indications Brain Tumor Hodgkins

LymphomaSide Effects Delayed

Myelosuppression

Pulmonary Toxicity

Streptozocin

Indications Pancreatic Cancer

 (Beta Cells)Side Effects GLUT-2 Transporter

Substrate, leading to lower levels of Insulin and a form of Type II Diabetes

Renal ToxicityDrug interactions Doxorubicin

ChlorozotocinEthylchloride

instead of methyl on nitrosourea

Not a GLUT-2 Transporter Substrate

Otherwise Per Streptozocin

7-Mitotic inhibitors-•Anti microtubule agent that

interefere with mitosis act during the late G2 phse and mitosis to stabilize microtubules, thus inhibiting cell division

Use of mitotic inhibitors in cytogenetics

• Cytogenetics, the study of chromosomal material by analysis of G-Banded chromosomes, uses mitotic inhibitors extensively. In order to prepare a slide for cytogenetic study, a mitotic inhibitor is added to the cells being studied.

• Specific agents• Taxanes• Taxanes are complex terpenes produced by the

plants of the genus Taxus (yews). Originally derived from the Pacific yew tree, they are now synthesized artificially. Their principal mechanism is the disruption of the cell's microtubule function by stabilizing microtubule formation. Microtubules are essential to mitotic reproduction, so through the inactivation of the microtubule function of a cell, taxanes inhibit the cell's division.

• Paclitaxel—used to treat lung cancer, ovarian cancer, breast cancer, and advanced forms of Kaposi's sarcoma.[5]

• Docetaxel—used to treat breast, ovarian, and non-small cell lung cancer•  

• Vinca alkaloids• Vinca alkaloids are amines

 produced by the hallucinogenic plant Catharanthus roseus (Madagascar Periwinkle). Vinca alkaloids inhibit microtubulepolymerization, thereby inhibiting mitosis.

• Vinblastine—used to treat leukaemia, Hodgkin's lymphoma, non-small cell lung cancer, breast cancer and testicular cancer. It is also a component in a large number of chemotherapy regimens.[8]

• Vincristine—used to treat lymphoma, breast cancer, lung cancer, and acute lymphoblastic leukemia.[8]

• Vindesine—used to treat leukaemia, lymphoma, melanoma, breast cancer, and lung cancer.[8]

• Vinorelbine—used to treat breast cancer and non-small-cell lung cancer

• Colchicine• Colchicine is an alkaloid derived from the autumn crocus (Colchicum autumnale). It inhibits mitosis by inhibiting microtubule polymerization. While colchicine is not used to treat cancer in humans, it is commonly used to treat acute attacks of gout

• Podophyllotoxin• Podophyllotoxin and Podophyllin,

derived from the may apple plant, are used to treat viral skin infections.• Griseofulvin• Griseofulvin, derived from a

Penicillium mold, is an antifungal drug.

• A mitotic inhibitor is a drug that inhibits mitosis, or cell division. These drugs disrupt microtubules, which are structures that pull the cell apart when it divides. Mitotic inhibitors are used in cancer treatment, because cancer cells are able to grow and eventually spread through the body (metastasize) through continuous mitotic division and so are more sensitive to inhibition of mitosis than normal cells

8-Corticosteroids-•Discrupt the cell membrain

and inhibit synthesis of protein,decrease circulting lymphocytes, inhibit mitosis.

• Discrupt the cell membrain and inhibit synthesis of protein,decrease circulting lymphocytes, inhibit mitosis.• Pharmacologic doses of steroid

inhibited growth of various tumor systems. Tissue culture studies confirmed that lymphoid cells were the most sensitive to glucocorticoids, and responded to treatment with decreases in DNA,

• ribonucleic acid (RNA), and protein synthesis. Studies of proliferating human leukemic lymphoblasts supported the hypothesis that glucocorticoids have preferential lymphocytolytic effects. The mechanism of action was initially thought to be caused by impaired energy use via decreased glucose transport and/or phosphorylation; it was later discovered that glucocorticoids induce apoptosis, or programmed cell death, in certain lymphoid cell populations

• Corticosteroids can be used to kill lymphoma, leukemia and multiple myeloma cells and may also be used to ease the side effects of other chemotherapy drugs. In addition to their chemotherapy action, corticosteroids also help reduce nausea, vomiting and allergic reactions caused by cancer treatment

9-Hormone therapy-•Selectively attach to estrogen receptors, cuasing downregulation of them and inhibiting tumor growth

Anticancer Agents: Hormones• Introduction• Breast and prostatic cancer: palliation with sex

hormone therapy• Adrenal corticosteroid treatment-- useful in:– acute leukemia– myeloma– lymphomas– other hematologic cancers

• Pharmacological effects:–Steroid hormones bind to steroid

receptors:–Efficacy of steroid treatment depends

on specific receptor presence on malignant cell surface.

• Clinical Use:Treatment of:–female and male breast cancer–prostatic cancer–endometrial cancer of uterus

• Adverse Effects:–Fluid retention (secondary to Na-retaining

properties)–Androgens-masculinization (long-term use)–Estrogens-feminization (long-term use)–Adrenocortical steroids:•hypertension•diabetes• enhanced susceptibility to infection• cushingoid appearance

• Estrogen and Androgen Inhibitors: (Tamoxifen and Flutamide)• Tamoxifen: Breast cancer treatment–Oral administration.–Activity against progesterone-

resistant endometrial neoplasm–Chemopreventive:women -- high-

risk for breast cancer

–Mechanism of Action:• Competitive partial agonist-inhibitor of

estrogen• Binds to estrogen-sensitive tissues (receptors

present)• Best antiestrogen effect requires minimal

endogenous estrogen presence {estradiol has a much higher affinity for the estrogen receptor than tamoxifen's affinity for the estrogen receptor}• Suppresses serum levels of insulin-like growth

factor-1; and up-regulates local TGF-beta production. These properties may explain tamoxifen antitumor activity in melanoma and ovarian cancer.

– Adverse Effects:• Generally mild• Most frequent: hot flashes• Occasionally: fluid retention, nausea

–  Clinical Use:• Advanced breast cancer–Most likely to be effective if:» lack endogenous estrogens {oophorectomy;

postmenopausal}» Presence of cytoplasmic estrogen

receptor;presence of cytoplasmic progesterone receptorColeman

• Prolongs survival {surgical adjuvant therapy} in postmenopausal women with estrogen receptor-positive breast cancer.

• Flutamide (Eulexin): prostatic cancer–Antagonizes remaining androgenic

effects after orchiectomy or leuprolide treatment

• Gonadotropin-Releasing Hormone Agonists (Leuprolide and Goserelin (Zoladex))• Leuprolide and goserelin: synthetic

peptide analogues of gonadotropin-releasing hormone (GnRH, LHRH)

–Mechanism of Action: Analogues more potent -- behave as GnRH agonists.• pituitary effects: when given continuously -- initial

stimulation then inhibition of follicle-stimulating hormone and leutinizing hormone.

•  Clinical Use: treating metastatic prostate carcinoma

• Comparing leuprolide with diethylstilbestrol (DES):– Similar suppression of androgens synthesis

and serum prostatic acid phosphatase .

– Adverse Effects: Leuprolide less frequently causes:•nausea• vomiting•edema• thromboembolism•painful gynecomastia

–Leuprolide and goserelin: medication more costly, the more cost-effective given reduced frequency of complications.

• Aromatase Inhibitors (Aminoglutethimide and Anastrozole (Arimidex))• Aminoglutethimide: –Mechanisms of action: Reduction in

estrogen concentration•Aminoglutethimide: inhibitor of adrenal steroid synthesis ( blocks conversion of cholesterol to pregnenolone {first-step})

• Aminoglutethimide inhibits extra-adrenal estradiol and estrone synthesis.• Aminoglutethimide inhibits an aromatase

enzyme {catalyzes conversion of androstenedione to estrone}–This conversion may occur in fat.

–Clinical Use:•Metastatic breast cancer (tumors contain

estrogen or progesterone receptors)–Aminoglutethimide is administered with

adrenalreplacement doses of hydrocortisone to ensure avoidance of adrenal insufficiency.

» Hydrocortisone is used in preference to dexamethasone, because dexamethasone increases the degradation of aminoglutethimide.

• Aminoglutethimide in combination with hydrocortisone: Second-Line Therapy for women treated with tamoxifen (aminoglutethimide causes more adverse side effects than tamoxifen)

• Anastrozole  (Arimidex): new, selective, nonsteroidal aromatase inhibitor.– appears to have no effect on glucocorticoid

or mineralocorticoid synthesis– Clinical Use:

• Treatment of advanced estrogen-or progesterone-receptor positive non--tamoxifen responsive breast cancer

10-Miscellneous-• Inhibite the protein synthesis,

enzymes derived from the yeast Enwinia used to deplete the supply of asparagines for leukemic cells that are dependent on exogenous source of this amino acid

Miscellaneous Anticancer Drugs• Amsacrine: – Hepatic metabolism– Mechanism of Action:• DNA intercalation: produces single-and double-strand breaks• interaction with topoisomerase II-DNA complexes

– Clinical Uses:• Anthracyclines- and cytarabine-resistant acute myelogenous

leukemia• Advanced ovarian cancer• Lymphomas

– Adverse Effects:• Does-limiting hepatic toxicity• Cardiac arrest has been noted with amsacrine infusion

• Asparaginase (El-spar):– Mechanism of action: depletion of serum asparagine

{forming aspartic acid and ammonia}• Decreased blood levels of asparagine and glutamine inhibit

protein synthesis in those neoplastic cells that express decreased levels of asparagine synthase.• Most normal cells express sufficient levels of asparagine

synthase to avoid toxicity.

• Hydroxyurea:– Mechanism of action:• Inhibits ribonucleotide reductase; depletes

deoxyribonucleoside triphosphate pools• Acts at S phase.

– Clinical Uses:• Melanoma [secondary role]• Chronic myelogenous leukemia [secondary role]

– Adverse Effects:• Bone marrow suppression• nausea• vomiting• diarrhea

• Mitoxantrone (Novantrone):– Mechanism of action:

• Induces DNA strand breaks• Inhibits RNA and DNA synthesis

– Clinical Uses:• Refractory acute leukemia• Pediatric and adult acute myelogenous leukemia• non-Hodgkin's lymphoma's• breast cancer

– Adverse Effects:• Dose-limiting: leukopenia• mild nausea• vomiting• stomatitis• alopecia• some cardiotoxicity {arrhythmias}

• Mitotane  (Lysodren):–  Clinical Use:Single indication-- adrenal

carcinoma• Reduces excessive steroid secretion

– Adverse Effects:• diarrhea• mental depression• skin eruption• anorexia• nausea• somnolence• dermatitis

• Retinoic acid Derivatives:– Clinical Uses:• Remissions -- acute promyelocytic

leukemia• 13-cis-Retinoic acid: chemopreventive --

second primary tumors in patients with hand and neck squamous cell carcinoma.

–  Adverse Effects:• skeletal effects• hepatic effects• teratogenic effects• mucocutaneous effects

• Bone Marrow Growth Factors (sargramostim and filgrastim):–Reduces neutropenic sepsis and other

complications of chemotherapy–Filgrastim shortens neutropenic state

following induction chemotherapy for acute nonlymphocytic leukemia.

• Amifostine • Cytoprotective from effects of chemotherapy

CONCEPT IN CHEMOTHERAPY• ADJUVANT CHEMOTHERAPY-• Adjuvant chemotherapy is the utilization of

antineoplastics agents in additionto surgery orradiotherapy. The rationale is to destroy cancer cells left behind in the operative field or disseminated through the blood stream to metastaticlocation.

• NEOADJUVANT CHEMOTHERAPY• It refers to the initial use of chemotherapy to

reduce the bulk and lower the stage of atumor, making it amenable to cure with subsequent localtherapy.

• COMBINATION CHEMOTHERAPY• It refers to the use of cytotoxic drugs in

combination. It isconsistently superior to single agent therapy.

ADMINISTRATION OF CHEMOTHERAPY

• Depending on clinical setting , chemotherapy may be administered by the physician,staffnurse or specialized team ember,such as the oncology clinical nurse specialist or intravenous therapist.

ROUTE OF ADMINISTRATION• 1-Oral • This rout is normally used for cyclophosphamide,

capecitabine drugs.• 2-Intramuscular• This rout is normally used for Bleomycin drug.• 3-Intravenous-• This rout is normally used for Daxarubicine,

vincristine,cisplatin, 5-fu drugs.

• 4- Intracavitary(pleural,peritoneal) –• This rout is normally used for radioisotopes ,

alklying agents, methotrexate.• 5-Intrathecal • For mithotraxate and cytarabine.• 6-Intraartical-• For DTIC,5-fu, Methotraxate.• 7-Perfusion • For alkylating agents

• 8-Continuous infusion-• For 5-fu,methotraxate and cytarabine.• 9-Subcutaneous-• For cytarabine• 10-Topical• For 5-fu crem.

TOXIC EFFCT OF CHEMOTHERAPY

• Toxicity associated with chemotherapy can be acue or chronic. Cell with rapid growth rates(e.g epithelium, bone marrow, hair follicles,and sperm) are very susceptible to damage from these agents. Varius body system may also be affected by these drugs

GASTROINTESTINAL SYSTEM• Nausea and voming• Anorexia• Taste alteration• Weight loss• Oral mucositis• Diarrhea• Constipation

HEMATOPIETIC SYSTEM

• Leukopenia•Anemia• Thrombocytopeniautropenia•Neutopenia• Increase risk of infection and

bleeding

INTEGUMETARY SYSTEM

• Alopesia• Skinreaction such as Red

patches(erythema),urticaria,• hyper pigmentation in the nailbeds, • mouth or gums or

teeth,Photosensitivity

REPRODUCTIVE SYSTEM• Testicular and ovarian function

impairedso result Azoospermia,oligospermia and sterility in male and• Amenorrhea,menopausal manifestations

and• sterility in female with increase risk of

abortion and fetal malformation.• In second and third trimester result low

birth weight or prematurity.

IMMUNE SYSTEM

•Risk for fatal infection•Stomatitis,enteritis,gingivitis and more infection•Fatique•Hair loss

Damage to specific organs may occur, with resultant symptoms:

• Cardiotoxicity (heart damage)• Hepatotoxicity (liver damage)• Nephrotoxicity (kidney damage)• Ototoxicity (damage to the inner ear),

producing vertigo• Encephalopathy (brain dysfunction)

Chemotherapy regimens Name Components

Example of uses, and other notes

ABVDAdriamycin (doxorubicin), bleomycin, vinblastine, dacarbazine

Hodgkin's lymphoma

ACAdriamycin (doxorubicin), cyclophosphamide

Breast cancer

BEACOPP

Bleomycin, etoposide, Adriamycin (doxorubicin), cyclophosphamide, Oncovin (vincristine), procarbazine,prednisone

Hodgkin's lymphoma

BEPBleomycin, etoposide, platinum agent (cisplatin)

Testicular cancer, germ cell tumors

CACyclophosphamide, Adriamycin (doxorubicin) (same as AC)

Breast cancer

CAFCyclophosphamide, Adriamycin (doxorubicin), fluorouracil (5-FU)

Breast cancer

CAVCyclophosphamide, Adriamycin (doxorubicin), vincristine

Lung cancer

CBVCyclophosphamide, BCNU (carmustine), VP-16 (etoposide)

Lymphoma

ChlVPP/EVA

Chlorambucil, vincristine (Oncovin), procarbazine, prednisone, etoposide, vinblastine, Adriamycin (doxorubicin)

Hodgkin's lymphoma

CHOP

Cyclophosphamide, hydroxydoxorubicin (doxorubicin), vincristine (Oncovin), prednisone

Non-Hodgkin lymphoma

CHOP-R or R-CHOP CHOP + rituximabB cell non-Hodgkin lymphoma

COP or CVPCyclophosphamide, Oncovin (vincristine), prednisone

Non-Hodgkin lymphoma in patients with history ofcardiovascular disease

CMFCyclophosphamide, methotrexate, fluorouracil (5-FU)

Breast cancer

COPP

Cyclophosphamide, Oncovin (vincristine), procarbazine, prednisone

Non-Hodgkin lymphoma

ECEpirubicin, cyclophosphamide

Breast cancer

ECFEpirubicin, cisplatin, fluorouracil (5-FU)

Gastric cancer and oesophageal cancer

EPEtoposide, platinum agent (cisplatin)

Testicular cancer, germ cell tumors

EPOCH

Etoposide, prednisone, Oncovin, cyclophosphamide, and hydroxydaunorubicin

Lymphomas

FECFluorouracil (5-FU), epirubicin, cyclophosphamide

Breast cancer

FL (Also known as Mayo)

Fluorouracil (5-FU), leucovorin (folinic acid)

Colorectal cancer

FOLFOXFluorouracil (5-FU), leucovorin (folinic acid), oxaliplatin

Colorectal cancer

FOLFIRIFluorouracil (5-FU), leucovorin (folinic acid), irinotecan

Colorectal cancer

ICEifosfamide, carboplatin, etoposide (VP-16)

Aggressive lymphomas, progressive neuroblastoma

ICE-R ICE + rituximabHigh-risk progressive or recurrent lymphomas

m-BACOD

Methotrexate, bleomycin, Adriamycin (doxorubicin), cyclophosphamide, Oncovin (vincristine), dexamethasone

Non-Hodgkin lymphoma

MACOP-B

Methotrexate, leucovorin (folinic acid), Adriamycin (doxorubicin), cyclophosphamide, Oncovin (vincristine),prednisone, bleomycin

Non-Hodgkin lymphoma

MOPPMechlorethamine, Oncovin (vincristine), procarbazine, prednisone

Hodgkin's lymphoma

MVACmethotrexate, vinblastine, adriamycin, cisplatin

Advanced bladder cancer[2]

PCVProcarbazine, CCNU (lomustine), vincristine

Brain tumors

ProMACE-MOPP

Methotrexate, Adriamycin (doxorubicin), cyclophosphamide, etoposide + MOPP

Non-Hodgkin lymphoma

ProMACE-CytaBOM

Prednisone, doxorubicin (adriamycin), cyclophosphamide, etoposide, cytarabine, bleomycin, Oncovin (vincristine),methotrexate, leucovorin

Non-Hodgkin lymphoma

R-FCMRituximab, fludarabine, cyclophosphamide, mitoxantrone

B cell non-Hodgkin lymphoma

Stanford V

Doxorubicin, mechlorethamine, bleomycin, vinblastine, vincristine, etoposide, prednisone

Hodgkin's lymphoma

Thal/DexThalidomide, dexamethasone

Multiple myeloma

TIPPaclitaxel, ifosfamide, platinum agent cisplatin

Testicular cancer, germ cell tumors in salvage therapy

VACVincristine, Actinomycin, Cyclophosphamide

Rhabdomyosarcoma

VAD

Vincristine, Adriamycin (doxorubicin), dexamethasone

Multiple myeloma

VAMPVincristine and others

Hodgkin's lymphoma, leukemia, multiple myeloma

VAPEC-B

Vincristine, Adriamycin (doxorubicin), prednisone, etoposide, cyclophosphamide, bleomycin

Hodgkin's lymphoma

VIPVinblastin, ifosfamide, platinum agent cisplatin

Testicular cancer, germ cell tumors

Care of the patient with chemotherapy

•Before care•During care•After care

RADIOTHERAPY• introduction•More than 60% of all clients with

cancer receive radiation therapy at some point during the course of their disease Radiation therapy may be used as a primary,adjuvant or palliative treatment modality.

• RT is the only treatment used and aims to achieve local cure of the cancer.• e.g. early stage Hodkin’s disease,

skincancer and carcinoma of cervix.

HISTORICAL BACKGROUND

• X-rays were discovered in 1885 by the German physicist,Wilhelm Conrad Roentgen, alsocalled the father of diagnostic radiology.

• Parallel to the discovery of X-rays, Becquerel discovered radioactivity in 1898.

• During the early 1900s,radiobiological experiments were conducted.

TYPES OF RADIATION• ionizing radiation• non-ionizing radiation• Photons (x-rays and gamma

rays),• Particle radiation

METHOD OF RADIATION • EXTERNAL RADIATION THERAPY • INTERNAL RADIATION THERAPY• A-SEALED SOURCE RADIOTHERAPY• B-UNSEALED SOURCE RADIATION

THERAPY• MULTI-FIELD THERAPT• CONFORMAL RADIATION

EXTERNAL RADIATIN THERAPY-

A-Conformal radiotherapy

• Conformal radiotherapy is a common type of external beam radiotherapy. It is also called 3D conformal radiotherapy (3D CRT). Conformal radiotherapy uses the same types of radiotherapy machine as standard beam external radiotherapy. But the radiotherapists put metal blocks in the path of the radiation beam. The blocks change the shape of the beam so that it ‘conforms’ more closely to the shape of the tumour.

B-Intensity modulated radiotherapy

• Intensity modulated radiation therapy (IMRT) uses hundreds of tiny devices called collimators to shape the radiotherapy area. The collimators also vary the intensity of the beams during each dose of treatment. The radiotherapy beams are aimed at the tumour from different directions. The collimators can move during treatment so that the machine gives very precise doses to a cancer or to specific areas within the tumour

C-Image guided radiotherapy

• In image guided radiotherapy (IGRT) CT, MRI, or PET scans are taken regularly during the treatment. The scans are processed by computers to show changes in the size and position of the tumour.

D-Tomotherapy

• Part of the tomotherapy machine can rotate completely around the patient to take CT scans and give radiotherapy to a very localised area.

E-Stereotactic radiotherapy and radiosurgery

• Stereotactic radiotherapy gives radiotherapy in fewer sessions, using smaller radiation fields and higher doses than 3D conformal radiotherapy. A single treatment of this type is sometimes called radiosurgery, Gamma Knife or Cyberknife

F- Proton therapy

• One of the newer ways of giving radiotherapy uses a different type of radiation beam called a proton beam. Protons collect energy as they slow down and travel through the body. They then release this energy at their target point – the tumour.

G-Electron beam radiotherapy

• Electron beams cannot travel very far through body tissue. This type of radiotherapy is used to treatskin cancers or tumours very close to the surface of the body.

• External radiation therapy may help relieve the problems caused by the tumors. Treatment may be done to the following body areas:

• Head and neck• Chest: • Arms and legs:• Bones• Abdomen:• Pelvic area

2-INTERNAL RADIATION THERAPY

• Internal radiotherapy is used mainly to treat cancers in the head and neck area, the cervix, womb, prostate or the skin.

• Treatment is given in one of two ways:• Brachytherapy - putting solid radioactive material

(the source) close to or inside the tumour for a limited period of time.

• Radioisotope treatment - by using a radioactive liquid, which is given either as a drink or as an injection into a vein

Brachytherapy

Radioisotope therapy

A-SEALED SOURCE RADIOTHERAPY

• brachytherapy /brachy·ther·a·py/ (-ther´ah-pe) treatment with ionizing radiation whose source is applied to the surface of the body or within the body a short distance from the area being treated

• Surface Applicator or "Mould" brachytherapy. • Interstitial brachytherapy. • Intracavitary brachytherapy places

the sources inside a pre-existing body cavity.

.B-UNSEALED SOURCE RADIATION THERAPY

•Unsealed source radiotherapy relates to the use of soluble forms of radioactivesubstances which are administered to the body by injection or ingestion.

• 1 Iodine• 2 Other unsealed sources• 3 Experimental antibody based methods - alpha emitters

Iodine

• • For example, iodine is an element selectively

taken up by the thyroid gland in healthy people. Thyroid disease (both benign conditions like thyrotoxicosis and malignant conditions like papillarythyroid cancer) can be treated with radioactive iodine (iodine-131) which is then concentrated into the thyroid. Iodine-131 produces beta and gamma radiation.

Other unsealed sources

Isotope Use Description

131I-MIBG (metaiodobenzylguanidine)

for the treatment of phaeochromocytoma andneuroblastoma

32P for overactive bone marrow

the main place of use of phosphorus is the bone marrow

89Sr & 153Smfor secondary cancer in the bones

strontium and samarium behave just like calcium

89Sr & 153Smfor secondary cancer in the bones

strontium and samarium behave just like calcium

90Yradiosynovectomy in the knee joint

Experimental antibody based methods - alpha emitters

• ITU work is being done on Alpha-Immunotherapy, this is an experimental method

MULTI-FIELD THERAPY

• In the planning of X-ray therapy the aim is to deliver a lethal dose to the lesion without doing significant harm to healthy tissue

CONFORMAL RADIATION T

• Three-Dimensional Conformal Radiation Therapy (3D-CRT)

• Tumors are not regular; they come in different shapes and sizes. Three-dimensional conformal radiation therapy, or 3D-CRT,

Common side effects of radiation therapy

• skin problems• fatigue from lack of sleep;• Diarrhea• Nausea and vomiting• Dry mouth• Trouble swallowing• Swelling• Hair loss• Sexual problems• Urinary and bladder changes

Site-specific side effects

• Head and neck• Chest.• Stomach and abdomen• Pelvis.

Nursing care of the patient

•Before care•During care•After care