1

CANCER CHEMOTHERAPY (Renal Cancers)

Cancer is characterized by uncontrolled gro th o! abnor"al cells# Cancer cells do not respond to the normal processes that regulate cell growth, proliferation, and survival, they can't carry out the physiologic functions of their normal mature cells.

$a"age to cellular $NA can result in "utation %cancer de&elo'"ent#

As normal cells ( The cell cycle contain 4 phases (S, M, 1, !" each responsi#le for a different tas$ necessary for cell division. 1. %uring the first activity phase, the M phase, the cell undergoes mitosis (cell division". !. Then, the cell enters the first gap or resting phase 1. %uring this the cell ma$es the en&ymes necessary for %'( synthesis. ). The synthesis of %'( occurs during the ne*t activity phase called S phase. 4. (fter that, the cell enters a second gap phase, resting !. +'( , other proteins are synthesi&ed during this phase to prepare for cell division during the M phase. A!ter that .. Continue to proceed through the cell cycle to divide again. /. Mature into speciali&ed cells , eventually die.

0. ( third resting phase o, proliferation of some normal cells under fine control to #alance the loss of mature functional cells with the production of new cells.

C)A**+,+CAT+ON O, ANT+ CANCER A-ENT* ./A)0Y)AT+N- A-ENT*( .) Nitrogen "ustards 1) Nitrosoureas 2) Al3yl sul!onates 4) Platinu" Coordination Co"'ounds Most useful agents- Nitrogen "ustards Cyclophosphamide (Cyto*an" o fosfamide

Secondary agents- Al3yl sul!onates Thiopeta (Thiople*" o 2varian cancer

o

Mechlorethamine Melphalan ((l$eran" Chloram#ucil (1eu$eran"

3rinary Cancer

4usulfan (Myleran"
o

Chronic myeloid leu$emia

Ma5or nitrosoureas

Carmustine (4C'3" 1omustine (CC'3" Semustine (methyl CC'3"

Poly!unctional Al3ylating $rugs( Mechanis" o! Action(

C('C6+ T76+(89:+(T766S7

(l$yl group transfer o Ma5or interaction- (l$ylation of %'(

8rimary %'( al$ylation site- '0 position of guanine (other sites as well" interaction may involve single strands or #oth strands (cross lin$ing, due to #ifunctional ;! reactive centers< characteristics"

o o

2ther interactions- these drugs react with car#o*yl, sulfhydryl, amino, hydro*yl, and phosphate groups of other cellular constituents These drugs usually form a reactive intermediate :: ethyleneimonium ion

Poly!unctional Al3ylating $rug Resistance

=ncreased a#ility to repair %'( defects %ecreased cellular permea#ility to the drug =ncreased glutathione synthesis
o

inactivates al$ylating agents through con5ugation reactions (cataly&ed #y glutathione S:transferase"

Phar"acological E!!ects( Poly!unctional Al3ylating $rugs

=n5ection site damage (vesicant effects" and systemic to*icity. To*icityo o

dose related primarily affecting rapidly dividing cells

#one marrow = tract

nausea and vomiting within less than an hour:: with mechlorethamine, carmustine (4C'3" or cyclophosphamide 6metic effects- C'S

reduced #y pre:treatment with phenothia&ines or canna#inoids.

Cyclophosphamide cytoto*icity depends on activation #y microsomal en&yme system.

7epatic microsomal 84.> mi*ed:function o*idase conversion of cyclophosphamide to the active forms

cataly&es

4:hydro*ycyclophosphamide aldophosphamide

Ma5or To*icity- #one marrow suppression

dose:related suppression of myelopoiesis- primary effects on

mega$aryocytes(#one marrow cells" platelets granulocytes

4one marrow suppression is worse when al$ylating agents are com#ined with other myelosuppressive drugs and?or radiation (dose reduction re@uired" =f #one marrow suppression is severe, treatment may have to #e suspended and then re:initiated upon hematopoietic recovery. 1ong:term conse@uences of al$ylating agent treatment include

ovarian failure (common" testicular failure (common" acute leu$emia (rare"

2ral +oute of (dministration-cyclophosphamide (Cyto*an", melphalan ((l$eran", chloram#ucil (1eu$eran", #usulfan (Myleran", lomustine (CC'3,Cee'3" Cyclophosphamide (Cyto*an"- most useful al$ylating agent at present. 4usulfan (Myleran"- specificity for granulocytes :: chronic myelogenous leu$emia Nitrosoureas(
o o o

not cross reactive ( with respect to tumor resistance" with other al$ylating drugs. 'onen&ymatic #y transformation re@uired to activate compounds. 7ighly lipid: solu#le:: crosses the #lood:#rain #arrier (444"

useful in treating #rain tumors

o o o o

(ct #y cross:lin$ing- %'( al$ylation More effective against cells in plateau phase than cells in e*ponential growth phase Ma5or route of elimination-urinary e*cretion Steptozocin:

sugar:containing nitrosourea minimal #one marrow suppression effective in insulin:secreting islet cell pancreatic carcinoma and sometimes in non:7odg$in's lymphoma

Other Al3ylating $rugs

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8rocar#a&ine (Matulane" o Methylhydra&ine derivative

o o o

(ctive in 7odg$in's disease (com#ination therapy" Teratogenic, mutagenic, leu$emogenic. Side effects

nausea, vomiting, myelosuppression hemolytic anemia pulmonary effects

%acar#a&ine (%T=C"
o

Clinical use

Melanoma(cancer of muscle,#ones" 7odg$in's disease(lymphoid cancer" soft tissue sarcoma

o o o

Synthetic drugA re@uires activation #y liver microsomal system. 8arenteral administration Side effects

nausea, vomiting, myelosuppression

Platinum Coordination Compounds

Cisplatin (Platinol) o Clinical use

Genitourinary cancers

testicular ovarian bladder

=n com#ination with #leomycin and vin#lastine- curative treatment for nonseminomatous testicular cancer Car#oplatin (less = and renal to*icityA with myelosuppressive to*icity"- alternative to cisplatin

o o o

=nhi#its %'( synthesisA cross:lin$ingA guanine '0 site 8latinum compounds- synergistic with other anticancer agents Site effects

ma5or acute effect- nausea, vomiting relatively little #one marrow effects

significant renal hydration?diuretics"

dysfunction

(minimi&ed

#y

ade@uate

acoustic nerve dysfunction(hearing"

Al3ylating Agent To5icity(

mechlorethamine, cyclophosphamide, carmustine- 'ausea and Bomiting (common" 2ral cyclophosphamide- 'ausea and Bomiting (less fre@uently" Most =mportant throm#ocytopenia
o

To*ic

6ffect-4one

marrow

suppression,

leu$openia,

secondary to myelosuppression ::

severe infection septicemia

hemorrhage

Cyclophosphamide (Cyto*an"-alopecia, hemorrhagic cystitis (may #e avoided #y ade@uate hydration"

1/ANT+ META6O)+TE( (S phase, cell cycle specific"

Methotre5ate (MT7)
o o o

Mechanism of (ction- Colic acid antagonist- acts at catalytic side of dihydrofolate reductase 8olyglutamate- important in methotre*ate action Tumor resistance to methotre*ate

decreased drug transport into the cell

C('C6+ T76+(89:+(T766S7

altered dihydrofolate reductase en&yme :: lower affinity for methotre*ate decreased polyglutamate formation @uantitative increase in dihydrofolate reductase en&yme concentration in the cell (gene amplification, increased message"

(dverse effects

4one marrow suppression %ermatologic = mucosa Adverse effects reversed by leucovorin (citrovorum factor)

1eucovorin DrescueD may #e used in cases of over dosage or in high:dose methotre*ate protocols

2ther uses

Treatment of rheumatoid arthritis =n com#ination with a prostaglandin- induces a#ortion

P8R+NE ANTA-ON+*T*
o o

/:Thiopurines (Mercaptopurine ;/:M8<A Thioguanine ;/:T <" Merca'to'urine (Purinethol)

Mechanism of (ction- (ctivation #y hypo*anthine:guanine phosphori#osyl transferase (7 8+T" to form /:thioinosinic acid which inhi#its en&ymes involved in purine meta#olism. (thioguanylic acid and /:methylmercaptopurine ri#otide (MM8+" also active" Clinical 3se

childhood acute leu$emia the analog, a&athioprine (=muran":: immunosuppressive agent.

Thioguanine

purine nucleotide pathway en&yme:inhi#itor

decreased intracellular concentration of guanine nucleotides inhi#ition of glycoprotein synthesis Mechanism of (ction- inhi#its %'(?+'( synthesis

Clinical 3se

Synergistic with cytara#ine in treating adult acute leu$emia.

%rug resistance

%ecreased 7 8+T activity

=n acute leu$emia :: increased al$aline phosphatase, which dephosphorylates thiopurines nucleotides

(dverse 6ffects

4oth mercaptopurine and thioguanine, given orally, are e*creted in the urine.

/:M8 is converted to an inactive meta#olite, /:thioruric acid, #y *anthine o*idase . =n cancer (hematologic" chemotherapy, allopurinol is used to inhi#it *anthine o*idase, to prevent hyperuricemia associated with tumor cell lysis E*anthine o*idase inhi#ition #loc$s purine degradation :: purines (more solu#le" are e*creted instead of uric acid (less solu#le"F

use of allopurinol thus #loc$s acute gout and nephroto*icity.

7owever, the com#ination of allopurinol and /: mercaptopurine, #ecause of *anthine o*idase inhi#ition, can lead to mercaptopurine to*icityA This interaction does not occur with /:T .

PYR+M+$+NE ANTA-ON+*T*(
o

Clurouracil (.:C3", normally given #y =B administration (oral a#sorption erratic"

4iotransformed to ri#osyl: and deo*yri#osyl: derivatives.

Mechanism of (ction

2ne derivative, .:fluoro:!':deo*yuridine .':phosphate (Cd3M8", inhi#its thymidylate synthase and its cofactor,a tetrahydrofolate derivative, resulting in inhi#ition of thymidine nucleotide synthesis. (nother derivative, .:fluorouridine triphosphate is incorporated into +'(, interfering with +'( function. Cytoto*icity-effects on #oth +'( and %'(

Clinical 3se- Systemically :: adenocarcinomasA Topically- s$in cancer Clo*uridine (C3%+"- similar to .:C3, used for hepatic artery infusion. Ma5or To*icity- myelosuppression, mucositis.

Cytara#ine (ara:C" =B administration

Mechanism of (ction-S phase:specific antimeta#olite

4iotransformed to active forms- ara:CT8, competitive inhi#itor of %'( polymerase.

C('C6+ T76+(89:+(T766S7

4loc$s %'( synthesisA no effect on +'( or protein synthesis

cytara#ine incorporated into +'( and %'( :: interfering with chain elongation

Clearance- deamination (inactive form" S phase specificity- highly schedule:dependent Clinical 3se- almost e*clusively for acute myelogenous leu$emia (dverse 6ffects

nausea alopecia stomatitis severe myelosuppression

P)ANT A)0A)O+$*# ./&inca al3aloids( ("Bin#lastin , BincristineMechanis" o! action( =nhi#ition of tubulin 'oly"eraization mitotic arrest leading to cell death. Microtu#ule- :a hollow tu#ular structure composed of the protein tu#ulin that helps to maintain the shape and movement of a living cell and the transportation of material within it.

To5icity ( 8hle#itis 9inblastin more potent as "yelosu'ressant(s'inal cord su''ression) 9incristine neuroto*icity ("ainly 'eri'heral neuro'athy: consti'ation.

Clinical uses o! 9inblastin % 9incristine(

Several pediatric tumors.

7ematological malignancies such as 7odg$in , non 7odg$in lymphoma , multiple myeloma. !:ta*ane family-

Eg. Paclitaxal

( al$aloid ester"

Mechanis" o! action o! Paclitaxal( Mitotic spindle poison.4ind to microtu#ules sta#ili&ing them in polymeri&ed state causing inhi#ition of mitosis , cell division. 8ses o! Paclitaxal( (dvanced ovarian , metastatic #reast cancer 'on small cell ,small cell lung cancer.

Ad&erse e!!ects o! Paclitaxal( The common triad 4M depression ( neutropenia" 7ypersensitivity reactions, .H of patients characteristic< 'euroto*icity 6dema in the legs

Podo'hylloto5ins (eto'oside ;9P/ .<=and teni'oside ;9M/1<=) o 6toposide and teniposide- structurally similar o Mechanism of action- 4loc$ cell cycle- in late S: ! phase inhi#ition of topoisomerase == :: %'( damage

o =B administration o 3rinary e*cretionA some in #ile o Clinical 3se 6toposide (B8:1/,Be8e:sid" o monocytic leu$emia testicular cancer lung carcinoma

Teniposide (Bumon"- lymphomas

(dverse 6ffects nausea

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vomiting alopecia significant hematopoietic to*icity and lymphoid to*icity

Ca"'tothecins (to'otecan and irinotecan ) o Mechanism of action- interfere with activity of topoisomerase = (cuts and religates single stranded %'(. %'( is damaged o Clinical 3ses Topotecan- metastatic ovarian cancer :: including cisplatin:resistant forms (as effective as paclita*el" (dverse 6ffects- Topotecan :: 8rimary o neutropenia o throm#ocytopenia o anemia 2ther o nausea o nominee o alopecia ANT+CANCER $R8-*( ANT+6+OT+C*

Clinically useful anticancer anti#iotics- derived from Streptomyces These anti#iotics act #yo

DNA intercalation, blocking synthesis of DNA and RNA ubex, Doxil) and Daunorubicin

Anthracyclines: Doxorubicin (Adriamycin, (Dauno!ome)

o o o

=B administrationA hepatic meta#olismA #iliary e*cretionA some urinary e*cretionA enterohepatic recirculation. (mong the most useful anticancer anti#iotics Mechanism of action

%'( intercalation :: #loc$ing synthesis of %'( and +'(A %'( strands scission :: #y affecting topoisomerase == (ltering mem#rane fluidity and ion transport Semi@uinone free radical causes an o*ygen radical generation.

Clinical 3seso

%o*oru#icin ((driamycin, +u#e*, %o*il":: very important anticancer agent I Carcinomas:%o*oru#icin

#reast carcinoma endometrial carcinoma

ovarian carcinoma testicular carcinoma Sarcomas:%o*oru#icin

thyroid carcinoma lung carcinoma

6wing's sarcoma

osteosarcoma 7ematologic Cancers:%o*oru#icin

+ha#domyosarcomas

acute leu$emia

multiple myeloma

7odg$in's disease

non:7odg$in's lymphoma

(d5uvant therapy in- osteogenic sarcoma and #reast cancer enerally used in com#ination protocols witho o o

cyclophosphamide (Cyto*an" cisplatin (8latinol" nitrosoureas

Ma5or 3se- (cute 1eu$emia %aunoru#icin- limited utility:: limited efficacy in treating solid tumors. =daru#icin- approved for acute myeloid leu$emia
o

=daru#icin in com#ination with cytara#ine- more active than daunoru#icin in inducing complete remission in acute myelogenous leu$emia.

(dverse 6ffectso o o

4one marrow depression (short duration" Cumulative, dose:related, possi#ly irreversi#le cardioto*icity. Total, severe alopecia %actinomycin (Cosmegen"
o o

=B administrationA .> percent remains unmeta#oli&ed. Mechanism of action- intercalation #etween guanine:cytosine #ase pairs

inhi#its %'(:dependent +'( synthesis #loc$s protein synthesis

Clinical 3ses-

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1)

dactinomycin in com#ination with vincristine (2ncovin"and surgery (may include radiotherapy" in treatment of Jilms' tumor dactinomycin with methotre*ate- may#e curative for locali&ed or disseminated gestational choriocarcinoma.

(dverse 6ffects

Ma5or dose limiting to*icity- #one marrow suppression (all #lood elements affected :: particularly platelets and leu$ocytes"

occasional severe throm#ocytopenia

nausea vomiting diarrhea oral ulcers %actinomycin- immunosuppressive (patient should not receive live virus vaccines" alopecia?s$in a#normalities interaction with radiation (Dradiation recallD"

Plica"ycin (Mithra"ycin)

Mechanism of action-#inds to %'( :: interrupts %'(:directed +'( synthesis

o

(lso decreases plasma calcium (independent tumor cell actionAacts on osteoclasts"

Clinical 3seso o

some efficacy in testicular cancer that is unresponsive to standard treatmentespecially useful in managing severe hypercalcemia associated with cancer

(dverse 6ffectso o o o o o

nausea vomiting throm#ocytopenia leu$openia hypocalcemia liver to*icity

.
o

#leeding disorders

Mitomycin- (Mutamycin"
o

Mechanism of action

meta#olic activation to produce a %'( al$ylating agent. Solid tumor hypo*ic stem cells may #e more sensitive to the action of mitomycin. 4est availa#le drug, in com#ination with *:rays, to $ill hypo*ic tumor cells.

Clinical 3se

in com#ination chemotherapy Ewith vincristine and #leomycinFs@uamous sell carcinoma of the cervi* adenocarcinoma of the stomach, pancreas, and lung {along with flurouracil and do orubicin!,urinary bladder" second:line drug- metastatic colon cancer topical intravesical treatment of small bladder papillomas"

(dverse 6ffects

Severe myelosuppression, especially after repeated doses, suggest action on hematopoietic stem cells. Bomiting anore*ia occasional nephroto*icity occasional interstitial pneumonitis

6leo"ycin (6leno5ane)

Mechanism of (ction-#inds to %'( :: produces single: and dou#le:strand #rea$s (free radical formation"
o o

Cell cycle specific- arrests division in ! Synergistic effects with vin#lastine and cisplatin (curative protocol for testicular cancer"

Clinical 3seso

4leomycin is used in the treatment of a num#er of different cancers, including cancer of the head and nec$, s$in, esophagus, lung, testis, and "enitourinary tract. S@uamous cell carcinoma- head, nec$, cervi*, s$in, penis, and rectum com#ination treatment- lymphoma

o o

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1.
o

intracavity treatment- malignant effusions in ovarian #reast cancer

(dverse 6ffectso o o o o

(naphylactoid reaction (potentially fatal" Cever anore*ia, #listering, hyper$eratosis (palms" pulmonary fi#rosis (uncommon" 'o significant myelosuppression

ANT+CANCER A-ENT*( HORMONE* =ntroduction

4reast and prostatic cancer- palliation with se* hormone therapy Adrenal corticosteroid treat"ent// use!ul ino o o o

acute leu$emia myeloma lymphomas other hematologic cancers

8harmacological effectso o

Steroid hormones #ind to steroid receptors6fficacy of steroid treatment depends on specific receptor presence on malignant cell surface.

Clinical 3se-Treatment ofo o o

female and male #reast cancer prostatic cancer endometrial cancer of uterus

(dverse 6ffectso o o o

Cluid retention properties"

(secondary

to

'a:retaining

(ndrogens:masculini&ation (long:term use" 6strogens:femini&ation (long:term use" (drenocortical steroids

hypertension

dia#etes enhanced suscepti#ility to infection cushingoid appearance

Estrogen and Androgen +nhibitors( (Ta"o5i!en and ,luta"ide)

Tamo*ifen- 4reast cancer treatment o 2ral administration.

o o o

(ctivity against progesterone:resistant endometrial neoplasm Chemopreventive-women :: high:ris$ for #reast cancer Mechanism of (ction

Competitive partial agonist:inhi#itor of estrogen 4inds to estrogen:sensitive tissues (receptors present" 4est antiestrogen effect re@uires minimal endogenous estrogen presence Eestradiol has a much higher affinity for the estrogen receptor than tamo*ifen's affinity for the estrogen receptorF Suppresses serum levels of insulin:li$e growth factor:1A and up: regulates local T C:#eta production. These properties may e*plain tamo*ifen antitumor activity in melanoma and ovarian cancer.

(dverse 6ffects

enerally mild Most fre@uent- hot flashes 2ccasionally- fluid retention, nausea

Clinical 3se

(dvanced #reast cancer

Most li$ely to #e effective if

lac$ endogenous postmenopausalF

estrogens

EoophorectomyA

8resence of cytoplasmic estrogen receptorApresence of cytoplasmic progesterone receptorColeman

8rolongs survival Esurgical ad5uvant therapyF in postmenopausal women with estrogen receptor:positive #reast cancer.

,luta"ide (Eule5in)( 'rostatic cancer

o

(ntagoni&es remaining androgenic effects after orchiectomy(removal of testcle"

-onadotro'in/Releasing Hor"one Agonists ()eu'rolide and -oserelin (>olade5)

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1euprolide and goserelin- synthetic peptide analogues of gonadotropin:releasing hormone ( n+7, 17+7" o Mechanism of (ction- (nalogues more potent :: #ehave as n+7 agonists.

pituitary effects- when given continuously :: initial stimulation then inhi#ition of follicle:stimulating hormone and leutini&ing hormone.

Causes reduced testicular androgen synthesis, the reason why these agents are effective in treating metastatic prostate carcinoma

Clinical 3se- treating metastatic prostate carcinoma

Miscellaneous Anticancer $rugs

(msacrineo 7epatic meta#olism

o

Mechanism of (ction

%'( intercalation- produces single:and dou#le:strand #rea$s interaction with topoisomerase ==:%'( comple*es

Clinical 3ses

(nthracyclines: and cytara#ine:resistant acute myelogenous leu$emia Advanced ovarian and renal cancer 1ymphomas

(dverse 6ffects

%oes:limiting hepatic to*icity Cardiac arrest has #een noted with amsacrine infusion

Mito5antrone (No&antrone)(
o

Mechanism of action

=nduces %'( strand #rea$s =nhi#its +'( and %'( synthesis

Clinical 3ses

+efractory acute leu$emia 8ediatric and adult acute myelogenous leu$emia non:7odg$in's lymphoma's #reast cancer

(dverse 6ffects %ose:limiting- leu$openia mild nausea

vomiting stomatitis alopecia some cardioto*icity EarrhythmiasF 6one Marro -ro th ,actors (sargra"osti" and !ilgrasti")(
o o

+educes neutropenic sepsis and other complications of chemotherapy Cilgrastim shortens neutropenic state following induction chemotherapy for acute nonlymphocytic leu$emia.

A"i!ostine
o

Cytoprotective from effects of chemotherapy

=MM3'2S388+6SS('T 1 lucocorticoids ! Cytoto*ic I I a: (l$ylating agents #: (ntimeta#olites 1 Methotre*ate !.(&athioprine and Mercaptopurine

). %rugs acting on immunophilins I I 1 Cyclosporin !. Sirolimus

$R8-* ACT+N- ON +MM8NOPH+)+N* Cyclosporin is a calcineurin inhi#itor. is one of the most widely used immunosuppressive drugs. =t is a fungal peptide, composed of 11 amino acids. Cyclosporin is thought to #ind to the cytosolic protein cyclophilin (an immunophilin" of immunocompetent lymphocytes, especially T:lymphocytes. This comple* of cyclosporin and cyclophilin inhi#its calcineurin, which under normal circumstances induces the transcription of interleu$in:!. The drug also inhi#its lympho$ine production and interleu$in release, leading to a reduced function of effector T:cells. Cyclosporin is used in the treatment of acute re5ection reactions, #ut has #een increasingly su#stituted with newer immunosuppressants, as it is nephroto*ic.

Sirolimus

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1G

Sirolimus is a macrolide lactone, produced #y the #treptomyce hygroscopicus =t is used to prevent re5ection reactions. (lthough it is a structural analogue of tacrolimus, it acts somewhat differently and has different side effects. Contrary to cyclosporine that affect the first phase of the T lymphocyte activation, sirolimus affects the second one, namely the signal transduction and their clonal proliferation. Therefore, sirolimus acts synergistically with cyclosporine and, in com#ination with other immunosuppressants, has few side effects. =ndirectly it inhi#its several T lympohocyte $inases and phosphatases, preventing the transmission of signal into their activity and the transition of the cell cycle from 1 to S phase. Similarly, it prevents the 4 cell differentiation to the plasma cells, which lowers the @uantity of =gM, =g and =g( anti#odies produced. =t acts immunoregulatory.

=MM3'2ST=M31('TS 4iologic therapy, also called immunostimulants, is a treatment that uses drugs to improve the way your #odyKs immune system fights disease. 9our immune system is your #odyKs natural defense against disease. ( healthy and strong immune system can detect the difference #etween healthy cells and cancer cells. $iologic therapy attempts to stimulate, or enhance the immune system so that it can fight the cancer. 1:Monoclonal (nti#odies Monoclonal anti#odies are proteins produced in the la#oratory from a single clone of a 4Lcell, the type of cells of the immune system that ma$e anti#odies. Jhen used as a treatment for cancer, there are three general strategies with monoclonal anti#odies 2ne uses the a#ility of the anti#odies to #ind to the cancer cells having the tumor antigens on their surface. The immune system will see the cancer cells mar$ed with #ound anti#odies as foreign and destroy them. ( second strategy is to use the anti#odies to #loc$ the #inding of cyto$ines or other proteins that are needed #y the cancerous cells to maintain their uncontrolled growth. Monoclonal anti#odies designed to wor$ li$e this #ind to the cyto$ine receptors that are on the tumor cell surface. ( final strategy involves special anti#odies that are lin$ed (con5ugated" to a su#stance that is deadly to the cancer cells. 6. . radioactive isotopes, have #een successfully con5ugated to anti#odies. The anti#odies are then used to specifically destroy he tumor cells with the radioactivity or to*ic su#stance.

Trastu&uma# Trastu&uma# is a humani&ed monoclonal anti#ody produced #y recom#inant %'( technology that #inds specifically to the human epidermal growth factor receptor ! protein (also $nown as 76+!" that is found on the cell surface of some cancer tumors, most nota#ly #reast cancer(!.L)>H of #reast malignancies" and also targets it for destruction #y the natural $iller cells of immune system.

1/6iological res'onse "odi!iers +esearchers have #een wor$ing on stimulating the immune cells during cancer with su#stances #roadly classified as #iological response modifiers. Cyto$ines are one such su#stance. These are proteins that are predominantly released #y immune cells upon activation or stimulation. (ldesleu$in Aldesleu#in is interleu#in, that is used to treat metastasis renal cell carcinoma (a $orm o$ #idney cancer) and metastasis melanoma% Aldesleu#in is also #no&n as interleu#in'(, )*'( Jhen renal cell carcinoma and metastasis melanoma (cancer of the s$in that arises in the pigmented cells of the s$in or eyes" do not respond to other therapies, they are candidates for treatment with aldesleu$in. (ldesleu$in is a #iological response modifier (4+M". =t promotes the development of T cells, or the cells in the lymphatic system that can fight cancer cells.

Side effect Clu:li$e symptoms (chills, fever, fatigue" 1oss of appetite S$in pro#lems such as a rash, itchiness, scaling Cardiac arrhythmias astrointestinal distur#ance, such as nausea and vomiting 'eurological effects, such as depression and poor concentration

+nter!erons =nterferons are small, natural cyto$ines that are produced #y leucocytes ,TLlymphocytes, and fi#ro#lasts in response to infection and other #iological stimuli. The goal of interferon use is to activate tumorLspecific cytoto*ic TLlymphocytes. Thus, tumor cells would #e destroyed #ased on immunotherapy. =nterferons attach to special receptors on the surface of cell mem#ranes. Then produce variety of functions including enhancing or inhi#iting en&ymes, decreasing cell proliferation, or enhancing the activity of macrophages and TLlymphocytes. There are several different classes of interferons, cancer therapy primarily focuses on alpha interferons.

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(lpha interferons are used to treat cancers such as hairy cell leu$emia, malignant melanoma, and Maposi's sarcoma (an (=%SLrelated cancer" as well as many other cancers *ide e!!ects

muscle aches, unusual metallic taste in the mouth, fever and chills, and general fluLli$e symptoms such as headache, loss of appetite (anore*ia", nausea and vomiting, and fatigue. To reduce the fluLli$e symptoms physicians may suggest that the patient ta$e acetaminophen #efore each dosage. confusion, trou#le thin$ing and focusing, mental depression, nervousness, or num#ness or tingling of fingers,

)e&a"isole 1evamisole act to restore depressed immune function. +t increases the res'onse o! T cells: or cells belonging to the ly"'hatic syste" that can !ight cancer cells# +t also see"s to increase the acti&ity o! cells that attac3 and destroy in&ading cancer cells: including both "onocytes and "acro'hages#

Side 6ffects (llergic reaction. %ecreased #one marrow function, resulting in fatigue or signs of infection 8ro#lems related to the nervous system, such as confusion, loss of consciousness, or speech distur#ances

C('C6+ T76+(89:+(T766S7