Chemotherapy involves the use of cytotoxic drugs to treat cancer. The goals of chemotherapy are to cure cancer, improve survival rates, or relieve symptoms. Key principles of chemotherapy include: (1) using drug combinations to increase efficacy and decrease resistance, (2) treating micrometastatic disease early on, and (3) dose intensity being important for response. Adjuvant chemotherapy after surgery or radiation has improved survival rates for several cancers like breast cancer and osteosarcoma by targeting remaining micrometastatic disease.

1. PRINCIPLES OF
CHEMOTHERAPY
Dr. R. RAJKUMAR M.D; D.M.Dr. R. RAJKUMAR M.D; D.M.
ASSISTANT PROF.& CONSULTANTASSISTANT PROF.& CONSULTANT
MEDICAL ONCOLOGISTMEDICAL ONCOLOGIST

2. ETIOLOGY OF
CANCER CarcinogenesisCarcinogenesis
 A cancer, is thought to developA cancer, is thought to develop
from a cell in which the normalfrom a cell in which the normal
mechanisms for control ofmechanisms for control of
growth and proliferation aregrowth and proliferation are
altered.altered.
 Current evidence supports theCurrent evidence supports the
concept of carcinogenesis as aconcept of carcinogenesis as a
multistage process that ismultistage process that is
genetically regulatedgenetically regulated

3. ETIOLOGY OF
CANCER
Genetic and Molecular Basis of CancerGenetic and Molecular Basis of Cancer
 Two major classes of genes are involved inTwo major classes of genes are involved in
carcinogenesis: oncogenes and tumorcarcinogenesis: oncogenes and tumor
suppressor genessuppressor genes

4. Invasivity
Motility
Aneuploidy
Angiogenesis
Imune Defense
Evasion
Deregulated
Proliferation
Altered Energy
Metabolism
Immortalization
(Anti-Apoptosis)
HallmarksHallmarks oof Cancerf Cancer
Target Areas for Therapeutic InterventionsTarget Areas for Therapeutic Interventions

5. MODALITIES OF
TREATMENT
 1-local therapy:1-local therapy:
 -surgery.-surgery.
 -radiation therapy.-radiation therapy.
 2-systemic treatment:2-systemic treatment:
 chemotherapy.chemotherapy.
 Hormonal therapyHormonal therapy..
 Monoclonal antibodies.Monoclonal antibodies.
 Radioactive material.Radioactive material.
 3-supportive care.3-supportive care.
 4-non-conventional therapy4-non-conventional therapy..

6. SURGERY
 Surgery was the first modality usedSurgery was the first modality used
successfully in the treatment ofsuccessfully in the treatment of
cancer.cancer.
 It is the only curative therapy for someIt is the only curative therapy for some
common solid tumors.common solid tumors.
 The most important determinant of aThe most important determinant of a
successful surgical therapy are thesuccessful surgical therapy are the
absence of distant metastases and noabsence of distant metastases and no
local infiltrationlocal infiltration..

7. Cont:
 Microscopic invasion of surroundingMicroscopic invasion of surrounding
normal tissue will necessitatenormal tissue will necessitate
multiple frozen section.multiple frozen section.
 Resection or sampling of regionalResection or sampling of regional
lymph node is usually indicated.lymph node is usually indicated.
 Surgery may be used for palliation inSurgery may be used for palliation in
patients for whom cure is notpatients for whom cure is not
possible.possible.
 Has significant role in cancerHas significant role in cancer
preventionprevention..
 E.gE.g familial polyposis coli.familial polyposis coli.

8. RADIATION THERAPY

9. RADIATION
THERAPY
 Radiation therapy: is a local modalityRadiation therapy: is a local modality
used in the treatment of cancer .used in the treatment of cancer .
 Success depend in the difference inSuccess depend in the difference in
the sensitivity between the tumor andthe sensitivity between the tumor and
normal tissue.normal tissue.
 It involves the administration ofIt involves the administration of
ionizing radiation in the form of x-rayionizing radiation in the form of x-ray
or gamma rays to the tumor site.or gamma rays to the tumor site.
 Method of delivery: ExternalMethod of delivery: External
beam(teletherapy). Internal beambeam(teletherapy). Internal beam
therapy(Brachytherapytherapy(Brachytherapy).).

10. Cont:
 Radiation therapy is planned andRadiation therapy is planned and
performed by a team of nurses,performed by a team of nurses,
dosimetrists,physician and radiationdosimetrists,physician and radiation
oncologist.oncologist.
 A course of radiation therapy isA course of radiation therapy is
preceded by a simulation session inpreceded by a simulation session in
which low-energy beam are used towhich low-energy beam are used to
produce radiograghic images thatproduce radiograghic images that
indicate the exact beam locationindicate the exact beam location..

11. Cont:
 Radiation therapy is usually deliveredRadiation therapy is usually delivered
in fractionated doses such as 180 toin fractionated doses such as 180 to
300 cGy per day,five times a week for300 cGy per day,five times a week for
a total course of 5-8 weeks.a total course of 5-8 weeks.
 Radiation therapy with curative intentRadiation therapy with curative intent
is the main treatment in limited stageis the main treatment in limited stage
Hodgkin’s disease , some NHL,Hodgkin’s disease , some NHL,
limited stage CA prostate, gynecologiclimited stage CA prostate, gynecologic
tumors & CNS tumortumors & CNS tumor ..
 Also can be used in palliative &Also can be used in palliative &
emergency setting.emergency setting.

12. COMPLICATION OF
RADIATION
 There are two types of toxicities - acute andThere are two types of toxicities - acute and
long term toxicity.long term toxicity.
 Systemic symptoms such as Fatigue , localSystemic symptoms such as Fatigue , local
skin reaction , GI toxicity , oropharyngealskin reaction , GI toxicity , oropharyngeal
mucositis , xerostomia & myelosuppression.mucositis , xerostomia & myelosuppression.
 Long-term sequelae: may occur manyLong-term sequelae: may occur many
months or years after radiation therapy.months or years after radiation therapy.
 Radiation therapy is known to be mutagenic,Radiation therapy is known to be mutagenic,
carcinogenic ,and teratogenic ,and havingcarcinogenic ,and teratogenic ,and having
increased risk of developing both secondaryincreased risk of developing both secondary
leukemia and solid tumorleukemia and solid tumor..

13. NUCLEAR MEDICINE

14. RADIONUCLIDES
 For decades have been usedFor decades have been used
systemically to treat malignantsystemically to treat malignant
disorders.disorders.
 They are administer by specialists inThey are administer by specialists in
nuclear medicine or radiationnuclear medicine or radiation
oncologist.oncologist.
 Radioactive iodine in the from ofRadioactive iodine in the from of 131131
I isI is
effective therapy for welleffective therapy for well
differentiated thyroid cadifferentiated thyroid ca
 Strontium-89. Is used for theStrontium-89. Is used for the
treatment of bony metastasis .It is antreatment of bony metastasis .It is an
alkaline earth element in the samealkaline earth element in the same
family as calciumfamily as calcium

15. CHEMOTHERAPY

16. Paul Ehrlich 1854 -
1915
• Father of Chemotherapy
• Salvarsan for Treatment
of Syphilis
• Nobel Prize 1908
• “Magic Bullet Concept”

17. HISTORICAL PERSPECTIVE
 Nitrogen mustards were a product ofNitrogen mustards were a product of
the secret war gas programs in boththe secret war gas programs in both
world warsworld wars
 In WWII, an explosion at Bar HarborIn WWII, an explosion at Bar Harbor
exposed seamen to mustard gas - theyexposed seamen to mustard gas - they
developed severe marrow anddeveloped severe marrow and
lymphoid hypoplasialymphoid hypoplasia
 Led to the useLed to the use of theseof these agents toagents to
treat Hodgkins and non-Hodgkinstreat Hodgkins and non-Hodgkins
lymphomas at Yale in 1943lymphomas at Yale in 1943

18. HISTORICAL PERSPECTIVE
 In the 1950’s, folic acid wasIn the 1950’s, folic acid was
shown to accelerate theshown to accelerate the
progression of childhoodprogression of childhood
leukemias; led to development ofleukemias; led to development of
folic acid antagonistsfolic acid antagonists
 In the 1960’s, combinationIn the 1960’s, combination
chemotherapy for childhoodchemotherapy for childhood
leukemias and Hodgkinsleukemias and Hodgkins
lymphoma began to be usedlymphoma began to be used

19. CHEMOTHERAPY
 Systemic chemotherapy is the mainSystemic chemotherapy is the main
treatment available for disseminatedtreatment available for disseminated
malignant diseases.malignant diseases.
 Progress in chemotherapy resulted inProgress in chemotherapy resulted in
cure for several tumors.cure for several tumors.
 Chemotherapy usually require multipleChemotherapy usually require multiple
cycles.cycles.

20. MODES OF CHEMOTHERAPY
 PRIMARY CHEMOTHERAPYPRIMARY CHEMOTHERAPY - chemotherapy- chemotherapy
is used as the sole anti-cancer treatment inis used as the sole anti-cancer treatment in
a highly sensitive tumor typesa highly sensitive tumor types
 Example – CHOP for Non-HodgkinsExample – CHOP for Non-Hodgkins
lymphomalymphoma
 ADJUVANT CHEMOTHERAPYADJUVANT CHEMOTHERAPY – treatment is– treatment is
given after surgery to “mop up” microscopicgiven after surgery to “mop up” microscopic
residual diseaseresidual disease
 Example – Adriamycin, cyclophosphamideExample – Adriamycin, cyclophosphamide
for breast cancerfor breast cancer
 NEOADJUVANT CHEMOTHERAPYNEOADJUVANT CHEMOTHERAPY ––
treatment is given before surgery to shrinktreatment is given before surgery to shrink
tumor and increase chance of successfultumor and increase chance of successful
resectionresection
 Example – Adriamycin, ifosfamide forExample – Adriamycin, ifosfamide for
osteosarcomaosteosarcoma

21. MODES OF
CHEMOTHERAPY
 CONCURRENT CHEMOTHERAPYCONCURRENT CHEMOTHERAPY ––
treatment is given simultaneous totreatment is given simultaneous to
radiation to increase sensitivity ofradiation to increase sensitivity of
cancer cells to radiationcancer cells to radiation
 Example – Cisplatin, 5-fluourouracil,Example – Cisplatin, 5-fluourouracil,
XRT for head and neck tumorsXRT for head and neck tumors

22. There is a wide variation in
sensitivity of various cancers
to chemotherapy
HighHigh IntermediateIntermediate LowLow
LymphomaLymphoma BreastBreast Head and neckHead and neck
LeukemiaLeukemia ColonColon ProstateProstate
Small Cell LungSmall Cell Lung
cancercancer
Non-small cell lungNon-small cell lung
cancercancer
GastricGastric
Testicular cancerTesticular cancer PancreaticPancreatic

23. CANCER CHEMOTHERAPY:
PRINCIPLES
1. The “Silver Bullet” isn’t out there1. The “Silver Bullet” isn’t out there..
2.2. Conventional chemotherapy targetsConventional chemotherapy targets
have been the cell cycle, microtubuleshave been the cell cycle, microtubules
and DNAand DNA
3. Combination chemotherapy improves3. Combination chemotherapy improves
responses over single agent, but doseresponses over single agent, but dose
intensity must be maintained.intensity must be maintained.

24. CANCER CHEMOTHERAPY:
PRINCIPLES
44.. It is better to treatIt is better to treat
micrometastatic diseasemicrometastatic disease
5. Phase I trials define an5. Phase I trials define an
MTD --a Maximum ToleratedMTD --a Maximum Tolerated
Dose - this may not equateDose - this may not equate
to the Maximum Therapeuticto the Maximum Therapeutic

25. CANCER CHEMOTHERAPY:
PRINCIPLES
6.6. For classical chemotherapy to beFor classical chemotherapy to be
effective, cell proliferation iseffective, cell proliferation is
required. Indolent (slowlyrequired. Indolent (slowly
growing) cancers are typicallygrowing) cancers are typically
resistant. If therapy isresistant. If therapy is
ineffective, tumor indolenceineffective, tumor indolence
determines survival.determines survival.
7.Almost7.Almost all who die with cancerall who die with cancer
have been treated withhave been treated with
chemotherapychemotherapy ---- thus drugthus drug
resistance is a major cause ofresistance is a major cause of

26. GOMPERTZIAN
GROWTH Growth rates are exponential atGrowth rates are exponential at
early stagesearly stages of development andof development and
slowerslower at later stages ofat later stages of
developmentdevelopment
Biological growth follows this characteristicBiological growth follows this characteristic
curve.curve.

27. GOMPERTZIAN GROWTH
MODEL
Initial tumour growth is first order, with
later growth being much slower
Smaller tumour grows slowly but large % of
cell dividing
Medium size tumour grows more quickly but
with smaller growth fraction
Large tumour has small growth rate and
growth fraction

29. AIM OF COMBINATION
CHEMOTHERAPY
INCREASED EFFICACYINCREASED EFFICACY
Different mechanisms of action Compatible side effects
Different mechanisms of resistance
ACTIVITYACTIVITY SAFETYSAFETY

30. PRINCIPLES OF
CHEMOTHERAPY
Rationale for combinationRationale for combination
chemotherapychemotherapy
 Different drugs exert their effectDifferent drugs exert their effect
through different mechanismsthrough different mechanisms
and at different stages of the celland at different stages of the cell
cycle, thus maximize cell killcycle, thus maximize cell kill
 Decease the chance of drugDecease the chance of drug
resistanceresistance

31. Combination chemotherapy:
Metastatic Breast
Cancer
Agents Dose Intensity PR (%)* CR (%)*
Cyclophosphamide 1 1 35 0
Methotrexate 1 1 25 0
Fluorouracil 1 1 25 0
Doxorubicin (A) 1 1 50 5
CMF 0.5+0.33+0.33 1.17 50 5
CAF 0.5+0.7+0.33 1.53 75 10
* Patients with overt metastases and no prior chemotherapy except in the
adjuvant setting
PR = partial response
CR = complete response
(“Cancer Medicine”, Holland and Frey (eds.), 5th
Ed., 2002)

32. CANCER CHEMOTHERAPY:
PRINCIPLES
More is better, to a point!
A
B
V
D
FFP: 81%
M
O
P
P/
A
B
V
FFP: 67%
A
B
V
D
FFP: 65%
M
O
P
P
FFP: 63%
S
I
N
G
L
E
A
G
E
N
T
FFP: 20%
Advanced Hodgkin’s Disease

33. Careful Sequencing is Critical
Docetaxel Doxorubicin
Doc Dox
40 mg/m2 50 mg/m2
Dox Doc
50 mg/m2 70 mg/m2
Itoh et al. Study of Sequence Switching of Administration
Clin. Cancer Res 6:4082-4090, 2000

34. CANCER CHEMOTHERAPY:
Adjuvant Chemotherapy Improves
Survival
Osteosarcoma: Sarcoma of the bone
1970’s: Surgery if no evidence of metastatic
disease
One-half developed metastatic disease,
Usually within 6 mos of surgery
20% 5 year survival.
Thus:80% had micrometastatic disease.
With adjuvant chemotherapy:
60-70% long-term survival

35. CANCER CHEMOTHERAPY:
adjuvant chemotherapy improves
survival
Breast Cancer C CMF ∆
Odds
1970’s: 3 yr RFS 1 -3 Nodes+ 64% 78% 39%
>3 Nodes+ 44% 49% 9%
CAF vs. CMF: 2% - 12% improvement reported
Widely adopted: Adriamycin + Cytoxan
Increasingly, followed by Taxol

37. Interphase Prophase Metaphase
Anaphase Interphase Cytokinesis
STAGES OF MITOSIS:

38. Cancer Chemotherapy
 After completion of mitosis, the resulting daughterAfter completion of mitosis, the resulting daughter
cells have two options:cells have two options:
 (1) they can either enter G1 & repeat the cycle or(1) they can either enter G1 & repeat the cycle or
 (2) they can go into G0 and not participate in the cell(2) they can go into G0 and not participate in the cell
cycle.cycle.
 Growth fraction - at any particular time some cellsGrowth fraction - at any particular time some cells
are going through the cell cycle whereas other cellsare going through the cell cycle whereas other cells
are resting.are resting.
 The ratio of proliferating cells to cells in G0, isThe ratio of proliferating cells to cells in G0, is
called the growth fraction.called the growth fraction.
 A tissue with aA tissue with a large percentage of proliferatinglarge percentage of proliferating
cellscells & few cells in& few cells in G0G0 has ahas a high growth fraction.high growth fraction.
 Conversely, a tissue composed ofConversely, a tissue composed of mostly of cells inmostly of cells in
G0G0 has ahas a low growth fractionlow growth fraction..

39. MECHANISMS OF CHEMOTHERAPY
 Damage the DNADamage the DNA of the affected cancerof the affected cancer
cells. It is not always possible to be selective, butcells. It is not always possible to be selective, but
selectivity is the ultimate goal of any drug.selectivity is the ultimate goal of any drug. e.g.e.g.,,
cisplatin (Platinol®), daunorubicin (Cerubidine®),cisplatin (Platinol®), daunorubicin (Cerubidine®),
doxorubicin (Adriamycin®), and etoposidedoxorubicin (Adriamycin®), and etoposide
(VePesid®).(VePesid®).
 Inhibit the synthesis of new DNAInhibit the synthesis of new DNA
strands to stop the cell from replicating, becausestrands to stop the cell from replicating, because
the replication of the cell is what allows the tumorthe replication of the cell is what allows the tumor
to grow.to grow. e.ge.g..,, methotrexate (Abitrexate®),methotrexate (Abitrexate®),
mercaptopurine (Purinethol®), fluorouracilmercaptopurine (Purinethol®), fluorouracil
(Adrucil®), and hydroxyurea (Hydrea®).(Adrucil®), and hydroxyurea (Hydrea®).
 Stop the mitotic processesStop the mitotic processes of a cell.of a cell.
Stopping mitosis stops cell division (replication) ofStopping mitosis stops cell division (replication) of
the cancer and may ultimately halt the progressionthe cancer and may ultimately halt the progression
of the cancer.of the cancer. e.g.e.g., Vinblastine (Velban®),, Vinblastine (Velban®),
Vincristine (Oncovin®)Vincristine (Oncovin®) and Pacitaxel (Taxol®).and Pacitaxel (Taxol®).

40. CLASSIFICATION OF
CYTOTOXIC DRUG
 Cytotoxic agent can be roughlyCytotoxic agent can be roughly
categorized based on theircategorized based on their
activity in relation to the cellactivity in relation to the cell
cycle.cycle.
p h a s e n o n s p e c ific . p h a s e s p e c ific
c y to to x ic d r u g

41. Cont :
 What is the difference between phaseWhat is the difference between phase
specific & phase non specific?…..specific & phase non specific?…..
 Phase non-specific:Phase non-specific:
 The drugs generally have a linearThe drugs generally have a linear
dose-response curve(dose-response curve(↑↑ the drugthe drug
administration ,theadministration ,the ↑↑ the fraction ofthe fraction of
cell killed).cell killed).
 Phase specific:Phase specific:
 Above a certain dosage level,furtherAbove a certain dosage level,further
increase in drug doesn’t result inincrease in drug doesn’t result in
more cell killing.but you can playmore cell killing.but you can play
with duration of infusion.with duration of infusion.

42. Two Broad Classes of
Chemotherapy Drugs:
 Cytotoxic agentsCytotoxic agents
 Cisplatin – causes DNA damageCisplatin – causes DNA damage
 5-Fluourouracil – blocks enzymes5-Fluourouracil – blocks enzymes
necessary for RNA and DNA synthesisnecessary for RNA and DNA synthesis
 Docetaxel – inhibits microtubuleDocetaxel – inhibits microtubule
formationformation
 Targeted therapiesTargeted therapies
 Erlotinib – small molecule inhibitor theErlotinib – small molecule inhibitor the
EGFR tyrosine kinaseEGFR tyrosine kinase
 Cetuximab – antibody that binds to EGFRCetuximab – antibody that binds to EGFR

43. CHEMOTHERAPEUTIC
AGENTS
 Alkylating agents:Alkylating agents:
 Antimetabolites:Antimetabolites:
 Antitumor antibiotic:Antitumor antibiotic:
 Plant alkaloidsPlant alkaloids::
 Other agentsOther agents
 Hormonal agent:Hormonal agent:
 Immunotherapy:Immunotherapy:

44. Chemotherapy – routes
of administration
 oraloral
 intravenousintravenous
 intramuscularintramuscular
 intrathecalintrathecal
 intraperitonealintraperitoneal
 intrapleuralintrapleural
►isolated organisolated organ
perfusionperfusion
►intrapericardialintrapericardial
 portal veinportal vein
 LimbLimb
intraarterialintraarterial

45. PLANNING DRUG DOSES
AND SCHEDULES
 DosesDoses
- based on body surface area- based on body surface area
- differ between children and adults- differ between children and adults
- adjusted for people who are elderly, have poor- adjusted for people who are elderly, have poor
nutritional status, have already taken or takingnutritional status, have already taken or taking
other medications, have already received orother medications, have already received or
are currently receiving radiation therapy, have loware currently receiving radiation therapy, have low
blood cell counts, or have liver or kidney diseasesblood cell counts, or have liver or kidney diseases

46. PLANNING DRUG DOSES
AND SCHEDULES
 Schedule (Cycles)Schedule (Cycles)
- A cycle = one dose followed by several- A cycle = one dose followed by several
days or weeks without treatment for normaldays or weeks without treatment for normal
tissues to recover from the drug’s side effectstissues to recover from the drug’s side effects
The number of cycles = based on the type andThe number of cycles = based on the type and
stage of cancer, and side effectsstage of cancer, and side effects

47. HEMATOLOGICAL
CONSIDERATIONS FOR DOSE
SCHEDULING
 LifespanLifespan
 Platelet - 7-10 daysPlatelet - 7-10 days
 Red blood cell - 120 daysRed blood cell - 120 days
 Neutrophils - 6-12 hoursNeutrophils - 6-12 hours
 Time from Stem Cell to Mature NeutrophilTime from Stem Cell to Mature Neutrophil
 ~7-10 days~7-10 days

48. DECIDING ON TREATMENT
INTERVALS
 As short as possibleAs short as possible
 Recovery of bone marrowRecovery of bone marrow
 Supplies mature cells for 8-10 daysSupplies mature cells for 8-10 days
 Onset 9-10th daysOnset 9-10th days
 Lowest (nadir) 14-18Lowest (nadir) 14-18thth
daysdays
 Recovery by day 21-28.Recovery by day 21-28.
 Usual schedule is q21-28 days.Usual schedule is q21-28 days.

49. COMPLICATION OF
CHEMOTHERAPY
 Every chemotherapeutic will have someEvery chemotherapeutic will have some
deleterious side effect on normal tissue .deleterious side effect on normal tissue .
 E.G; Myelosuppression,nausea&vomiting,E.G; Myelosuppression,nausea&vomiting,
Stomatitis,and alopecia are the mostStomatitis,and alopecia are the most
frequently observed side effects.frequently observed side effects.

50. MucositisMucositis
Nausea/vomitingNausea/vomiting
DiarrheaDiarrhea
CystitisCystitis
SterilitySterility
MyalgiaMyalgia
NeuropathyNeuropathy
Alopecia
Pulmonary fibrosis
Cardiotoxicity
Local reaction
Renal failure
Myelosuppression
Phlebitis
SIDE EFFECTS OF CHEMOTHERAPYSIDE EFFECTS OF CHEMOTHERAPY

51. CRITERIA USED TO
DESCRIBE RESPONSE ARE:
 Complete response (complete remission)is(complete remission)is
the disappearance of all detectablethe disappearance of all detectable
malignant disease.malignant disease.
 Partial response : is decrease by more than: is decrease by more than
50% in the sum of the products of the50% in the sum of the products of the
perpendicular diameters of all measurableperpendicular diameters of all measurable
lesions.lesions.
 Stable disease : no increase in size of any: no increase in size of any
lesion nor the appearance of any newlesion nor the appearance of any new
lesionslesions..
 Progressive disease : means an increase by: means an increase by
at least 25% in the sum of the products ofat least 25% in the sum of the products of
the perpendicular diameters of measurablethe perpendicular diameters of measurable
lesion or the appearance of newlesion or the appearance of new lesions.lesions.

52. Methods to increase
the efficacy of
chemotherapy
 standard dosingstandard dosing
 high dosehigh dose
 dose-densedose-dense

53. ENDOCRINE THERAPY

54. ENDOCRINE THERAPY
 Many hormonal antitumor agents are functional agonist orMany hormonal antitumor agents are functional agonist or
antagonist of the steroid hormone family.antagonist of the steroid hormone family.
 Adrenocorticoids:Adrenocorticoids:
 Antiandrogen:Antiandrogen:
 Estrogen:Estrogen:
 Antiestrogen:Antiestrogen:
 ProgestinsProgestins
 Aromatase inhibitor:Aromatase inhibitor:
 Gonadotropin-releasing hormone agonists:Gonadotropin-releasing hormone agonists:
 Somatostatin analogues:Somatostatin analogues:

55. ADRENOCORTICOSTEROID
 Are frequently used in combination regimen forAre frequently used in combination regimen for
the treatment of lymphocytic leukemia andthe treatment of lymphocytic leukemia and
lymphoma.lymphoma.
 They function by binding to glucocorticoid-They function by binding to glucocorticoid-
specific receptors present in lymphoid cells andspecific receptors present in lymphoid cells and
initiate programmed cell deathinitiate programmed cell death
 They most commonly used agent areThey most commonly used agent are
prednisone,methylprednisone,dexamethosone.prednisone,methylprednisone,dexamethosone.

56. ANTIANDROGENS
 Flutamide :Flutamide :
Effectively blocks the binding of androgen toEffectively blocks the binding of androgen to
its receptor in the periphral tissue .its receptor in the periphral tissue .
It is used in the treatment of disseminatedIt is used in the treatment of disseminated
prostate caprostate ca

57. BIOLOGIC THERAPY
 Immunotherapy:Immunotherapy:
 CytokinesCytokines
 Cellular therapy.Cellular therapy.
 Tumor vaccine:Tumor vaccine:
 Hematopoietic growth factors.Hematopoietic growth factors.

58. Definition
New technology and drugs that allow the
cancer treatment to “target” a certain cancer cell
by interfering with the natural functions of tumor
growth
How they work
They “target” specific parts of a cancer cell or
its actions; hand in a glove analogy
What it means in cancer treatment
 Potentially fewer side effects
“TARGETED” THERAPIES

59. Targeted Therapies

60. SIGNALLING PATHWAYS

61. TARGETED THERAPIES
 Monoclonal antibodiesMonoclonal antibodies: proteins that trigger the: proteins that trigger the
body’s pathways involved in cancer growth tobody’s pathways involved in cancer growth to
fight cancer more effectively.fight cancer more effectively.
 EGFREGFR: family of receptors found on surface of: family of receptors found on surface of
normal and cancer cells that bind with annormal and cancer cells that bind with an
epidermal growth factor (EGF) causing cells toepidermal growth factor (EGF) causing cells to
divide.divide.
 Tyrosine Kinase InhibitorsTyrosine Kinase Inhibitors: Part of the cell that: Part of the cell that
signals it to divide and multiply; enhances cellsignals it to divide and multiply; enhances cell
growth. Still investigationalgrowth. Still investigational

62. TK TKATP ATP
CellCell
ProliferationProliferation
AntiapoptosiAntiapoptosi
ss
AngiogenesisAngiogenesis
Gene Transcription
Cell Cycle
Progression
+
MetastasesMetastasesSurvivalSurvival
Tumor Cell StimulationTumor Cell Stimulation

63. TK TK TK
Strategies to Inhibit Signaling
--
-- --
tyrosinetyrosine
kinasekinase
inhibitorsinhibitors
““-ibs”-ibs”
Anti- mAbsAnti- mAbs
““-mab”-mab”
Anti-ligandAnti-ligand
mAbsmAbs
““-mab”-mab”
ATP

64. CONCLUSIONS
 People with cancer are living longerPeople with cancer are living longer
 The focus is on quality of life in addition toThe focus is on quality of life in addition to
quantityquantity
 People surviving cancer want to live normal livesPeople surviving cancer want to live normal lives
 New treatments of various kinds are available andNew treatments of various kinds are available and
there is no need to sufferthere is no need to suffer