Principles of chemotherapy ppt

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

2. ETIOLOGY OF
CANCER
CarcinogenesisCarcinogenesis

A cancer, is thought to develop A cancer, is thought to develop
from a cell in which the normal from a cell in which the normal
mechanisms for control of mechanisms for control of
growth and proliferation are growth and proliferation are
altered. altered.

Current evidence supports the Current evidence supports the
concept of carcinogenesis as a concept of carcinogenesis as a
multistage process that is multistage 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 in Two major classes of genes are involved in
carcinogenesis: oncogenes and tumor carcinogenesis: oncogenes and tumor
suppressor genessuppressor genes

4. Invasivity
Motility
Aneuploidy
Angiogenesis
Imune Defense
Evasion
Deregulated
Proliferation
Altered Energy
Metabolism
Immortalization
(Anti-Apoptosis)
Hallmarks Hallmarks 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 used Surgery was the first modality used
successfully in the treatment of successfully in the treatment of
cancer.cancer.
It is the only curative therapy for some It is the only curative therapy for some
common solid tumors.common solid tumors.
The most important determinant of a The most important determinant of a
successful surgical therapy are the successful surgical therapy are the
absence of distant metastases and no absence of distant metastases and no
local infiltrationlocal infiltration..

7. Cont:
Microscopic invasion of surrounding Microscopic invasion of surrounding
normal tissue will necessitate normal tissue will necessitate
multiple frozen section.multiple frozen section.
Resection or sampling of regional Resection or sampling of regional
lymph node is usually indicated.lymph node is usually indicated.
Surgery may be used for palliation in Surgery may be used for palliation in
patients for whom cure is not patients for whom cure is not
possible.possible.
Has significant role in cancer Has 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 modality Radiation therapy: is a local modality
used in the treatment of cancer .used in the treatment of cancer .
Success depend in the difference in Success depend in the difference in
the sensitivity between the tumor and the sensitivity between the tumor and
normal tissue.normal tissue.
It involves the administration of It involves the administration of
ionizing radiation in the form of x-ray ionizing radiation in the form of x-ray
or gamma rays to the tumor site.or gamma rays to the tumor site.
Method of delivery: External Method of delivery: External
beam(teletherapy). Internal beam beam(teletherapy). Internal beam
therapy(Brachytherapytherapy(Brachytherapy ). ).

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

11. Cont:
Radiation therapy is usually delivered Radiation therapy is usually delivered
in fractionated doses such as 180 to in fractionated doses such as 180 to
300 cGy per day,five times a week for 300 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 intent Radiation therapy with curative intent
is the main treatment in limited stage is the main treatment in limited stage
Hodgkin’s disease , some NHL, Hodgkin’s disease , some NHL,
limited stage CA prostate, gynecologic limited stage CA prostate, gynecologic
tumors & CNS tumor tumors & 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 and There are two types of toxicities - acute and
long term toxicity.long term toxicity.
Systemic symptoms such as Fatigue , local Systemic symptoms such as Fatigue , local
skin reaction , GI toxicity , oropharyngeal skin reaction , GI toxicity , oropharyngeal
mucositis , xerostomia & myelosuppression.mucositis , xerostomia & myelosuppression.
Long-term sequelae: may occur many Long-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 having carcinogenic ,and teratogenic ,and having
increased risk of developing both secondary increased risk of developing both secondary
leukemia and solid tumorleukemia and solid tumor..

13. NUCLEAR MEDICINE

14. RADIONUCLIDES
For decades have been used For decades have been used
systemically to treat malignant systemically to treat malignant
disorders.disorders.
They are administer by specialists in They are administer by specialists in
nuclear medicine or radiation nuclear medicine or radiation
oncologist.oncologist.
Radioactive iodine in the from of Radioactive iodine in the from of
131131
I is I is
effective therapy for well effective therapy for well
differentiated thyroid ca differentiated thyroid ca
Strontium-89. Is used for the Strontium-89. Is used for the
treatment of bony metastasis .It is an treatment of bony metastasis .It is an
alkaline earth element in the same alkaline earth element in the same
family as calcium family 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 of Nitrogen mustards were a product of
the secret war gas programs in both the secret war gas programs in both
world warsworld wars
In WWII, an explosion at Bar Harbor In WWII, an explosion at Bar Harbor
exposed seamen to mustard gas - they exposed seamen to mustard gas - they
developed severe marrow and developed severe marrow and
lymphoid hypoplasialymphoid hypoplasia

Led to the use Led to the use of these of these agents to agents to
treat Hodgkins and non-Hodgkins treat Hodgkins and non-Hodgkins
lymphomas at Yale in 1943lymphomas at Yale in 1943

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

19. CHEMOTHERAP Y
Systemic chemotherapy is the main Systemic chemotherapy is the main
treatment available for disseminated treatment available for disseminated
malignant diseases.malignant diseases.
Progress in chemotherapy resulted in Progress in chemotherapy resulted in
cure for several tumors.cure for several tumors.
Chemotherapy usually require multiple Chemotherapy usually require multiple
cycles.cycles.

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

21. MODES OF
CHEMOTHERAPY
CONCURRENT CHEMOTHERAPY CONCURRENT CHEMOTHERAPY – –
treatment is given simultaneous to treatment is given simultaneous to
radiation to increase sensitivity of radiation 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 Lung Small Cell Lung
cancercancer
Non-small cell lung Non-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 targets Conventional chemotherapy targets
have been the cell cycle, microtubules have been the cell cycle, microtubules
and DNAand DNA
3. Combination chemotherapy improves 3. Combination chemotherapy improves
responses over single agent, but dose responses over single agent, but dose
intensity must be maintained.intensity must be maintained.

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

25. CANCER CHEMOTHERAPY:
PRINCIPLES
6.6.For classical chemotherapy to be For classical chemotherapy to be
effective, cell proliferation is effective, cell proliferation is
required. Indolent (slowly required. Indolent (slowly
growing) cancers are typically growing) cancers are typically
resistant. If therapy is resistant. If therapy is
ineffective, tumor indolence ineffective, tumor indolence
determines survival.determines survival.
7.Almost 7.Almost all who die with cancer all who die with cancer
have been treated with have been treated with
chemotherapy chemotherapy -- -- thus drug thus drug
resistance is a major cause of resistance is a major cause of
death. Drug resistance can stem death. Drug resistance can stem
from host, tumor and cellular from host, tumor and cellular
factors.factors.

26. GOMPERTZIAN
GROWTH
Growth rates are exponential at Growth rates are exponential at
early stages early stages of development andof development and
slowerslower at later stages of at later stages of
developmentdevelopment
Biological growth follows this characteristic Biological 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 combination Rationale for combination
chemotherapychemotherapy
Different drugs exert their effect Different drugs exert their effect
through different mechanisms through different mechanisms
and at different stages of the cell and at different stages of the cell
cycle, thus maximize cell killcycle, thus maximize cell kill
Decease the chance of drug Decease 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.), 5
th
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 daughter After 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 cells Growth fraction - at any particular time some cells
are going through the cell cycle whereas other cells are going through the cell cycle whereas other cells
are resting. are resting.
The ratio of proliferating cells to cells in G0, is The ratio of proliferating cells to cells in G0, is
called the growth fraction. called the growth fraction.
A tissue with a A tissue with a large percentage of proliferating large percentage of proliferating
cellscells & few cells in & few cells in G0G0 has a has a high growth fraction. high growth fraction.
Conversely, a tissue composed of Conversely, a tissue composed of mostly of cells in mostly of cells in
G0G0 has a has a low growth fractionlow growth fraction..

39. MECHANISMS OF CHEMOTHERAPY
Damage the DNADamage the DNA of the affected cancer of the affected cancer
cells. It is not always possible to be selective, but cells. 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 etoposide doxorubicin (Adriamycin®), and etoposide
(VePesid®). (VePesid®).
Inhibit the synthesis of new DNAInhibit the synthesis of new DNA
strands to stop the cell from replicating, because strands to stop the cell from replicating, because
the replication of the cell is what allows the tumor the replication of the cell is what allows the tumor
to grow. to grow. e.ge.g.., , methotrexate (Abitrexate®), methotrexate (Abitrexate®),
mercaptopurine (Purinethol®), fluorouracil mercaptopurine (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) of Stopping mitosis stops cell division (replication) of
the cancer and may ultimately halt the progression the 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 roughly Cytotoxic agent can be roughly
categorized based on their categorized based on their
activity in relation to the cell activity in relation to the cell
cycle.cycle.
p h a s e n o n s p e c i f i c . p h a s e s p e c i f i c
c y t o t o x i c d r u g

41. Cont :
What is the difference between phase What is the difference between phase
specific & phase non specific?…..specific & phase non specific?…..
Phase non-specific: Phase non-specific:

The drugs generally have a linear The drugs generally have a linear
dose-response curve(dose-response curve(­­ the drug the drug
administration ,the administration ,the ­­ the fraction of the fraction of
cell killed).cell killed).
Phase specific:Phase specific:

Above a certain dosage level,further Above a certain dosage level,further
increase in drug doesn’t result in increase in drug doesn’t result in
more cell killing.but you can play more 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 enzymes 5-Fluourouracil – blocks enzymes
necessary for RNA and DNA synthesisnecessary for RNA and DNA synthesis

Docetaxel – inhibits microtubule Docetaxel – inhibits microtubule
formationformation
Targeted therapiesTargeted therapies

Erlotinib – small molecule inhibitor the Erlotinib – 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
oral oral
intravenousintravenous
intramuscularintramuscular
intrathecalintrathecal
intraperitonealintraperitoneal
intrapleuralintrapleural
►isolated organ isolated organ
perfusionperfusion
►intrapericardialintrapericardial
portal veinportal vein
LimbLimb
intraarterialintraarterial

45. PLANNING DRUG DOSES
AND SCHEDULES
Doses Doses
- 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 taking nutritional status, have already taken or taking
other medications, have already received or other medications, have already received or
are currently receiving radiation therapy, have low are 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 normal days 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 and The 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 days Supplies mature cells for 8-10 days

Onset 9-10th daysOnset 9-10th days

Lowest (nadir) 14-18Lowest (nadir) 14-18
thth
days days

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 some Every 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 most Stomatitis,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 detectable the 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 the 50% in the sum of the products of the
perpendicular diameters of all measurable perpendicular 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 new lesion 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 of at least 25% in the sum of the products of
the perpendicular diameters of measurable the perpendicular diameters of measurable
lesion or the appearance of new lesion 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 or Many 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 for Are frequently used in combination regimen for
the treatment of lymphocytic leukemia and the 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 and specific receptors present in lymphoid cells and
initiate programmed cell deathinitiate programmed cell death
They most commonly used agent are They most commonly used agent are
prednisone,methylprednisone,dexamethosone. prednisone,methylprednisone,dexamethosone.

56. ANTIANDROGENS
Flutamide :Flutamide :
Effectively blocks the binding of androgen to Effectively 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 disseminated It 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 to body’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 an normal and cancer cells that bind with an
epidermal growth factor (EGF) causing cells to epidermal 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 cell signals it to divide and multiply; enhances cell
growth. Still investigationalgrowth. Still investigational

62. TK TK
ATP ATP
Cell Cell
ProliferationProliferation
AntiapoptosiAntiapoptosi
ss
AngiogenesisAngiogenesis
Gene Transcription
Cell Cycle
Progression
+
MetastasesMetastases
SurvivalSurvival
Tumor Cell StimulationTumor Cell Stimulation

63. TK TK TK
Strategies to Inhibit Signaling
--
-- --
tyrosine tyrosine
kinase kinase
inhibitorsinhibitors
““-ibs”-ibs”
Anti- mAbsAnti- mAbs
““-mab”-mab”
Anti-ligand Anti-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 to The 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 and New treatments of various kinds are available and
there is no need to sufferthere is no need to suffer