farmakologi anti kanker
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FARMAKOLOGI
OBAT ANTI KANKERPSFKKO
Universitas Gadjah Mada2014
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* CELL - CYCLE SPECIFIC DRUGS : = phase non specific
Paling efektif jika cell tersebut aktif dalamcell cycle
- Class Type ObatAlkylating Nitrogen mustard Chlorambucil, cyclophosphamide
agent MelphalanAlkyl sulfonate BusulfanTriazine DTICMetal salt Cisplatin
Natural product Antibiotic Actinomycin -D
DaunorubicinDoxorubicin
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Identify Candidate Compounds
Screening
Preclinical Evaluation
Production and Formulation
Phase I, II, III, IV Clinical Trials
General Medical Practice
Toxicology Pharmacology Biochemistry
ONCOLOGYDrug development
Steps in cancer drug development
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Procedure for the Development, Testing and Use of Chemotherapeutic Drugs
Drugs Development
Random Screening Logical Design
Animal Data
Formulation
Phase 1 Trials (Toxicity maximum tolerateddose)Phase 2 Trials (Efficacy in different tumours)
Phase 3 Trials (Comparative Randomizedstudies)
Clinically Useful New Agent
Use AsAdjuvant If
Circumstances Exist
Combine With OtherActive Agent In
Advanced Disease
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ONCOLOGYDrug development
Identification of candidate compounds: Natural products
Drug Type Source
Antitumor antibiotic (daunorubicin, doxorubicin) Streptomyces fungus
Vinca alkyloid (vincristine, vinblastine) Vinca rosea plant
Taxane Yew tree
Camptothecin (topotecan, CPT-11) Camptotheca accuminata tree
Podophyllin (etoposide, teniposide) Podophyllum peltatum plant
Bryostatin, dolastatin, halichondrin Marine organisms
Grever MR, Chabner BA. Cancer: Principles & Practice of Oncology . 1997;387-388.Haskell CM. Cancer Treatment . 1995;35-36.
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Grever MR, Chabner BA. Cancer: Principles & Practice of Oncology . 1997;385-394.
Identification of candidate compounds: Molecular-targeted screening
ONCOLOGYDrug development
Computer-aided construction ofmolecules
Mutant oncogenes (BCR-ABL)Aberrant tumor suppressor genes (RB)
Protein kinases
Transcription activators
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Prostate
IN VITRO HUMAN TUMOR CELL LINE PANELS
OvarianMelanomaCNSBreastColonLung
Preclinical developmentfollowed by broad-based clinical trials
In Vivo tumor panel human tumor xenograft studies
Specific disease -oriented Phase I/II trials
Targeted preclinical development
Nonspecific antitumor activity Highly specific antitumor activity
Adapted from NCI drug screening strategy,1985.
ONCOLOGYDrug development
Screening for anticancer activity
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ONCOLOGYDrug development
Target level Maximum tolerated dose Spectrum of activity
Cellular level Dose-limiting toxicities Schedule dependency
Efficacy Route administration
Cross resistance
Combination therapies
IN VITRO IN VIVO
Preclinical evaluation of cytotoxic agents
Mechanis m of act ion Stage I Stage II
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ONCOLOGYDrug development
Preclinical studies in mice, rats,and dogs provide an importantbridge from in vitro studies toclinical studies
Objectives Define major toxicities Identify initial safe starting dose
for clinical trials
Use of animal models in evaluation of cytotoxic agents
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Study Phase Objectives Patient Population
Phase I Identify maximum tolerated dose Small (3-6 patients/dose level) Define key toxicities Various tumor types
Phase II Evaluate tumor response Larger than Phase I (10-50 Determine whether drug patients/treatment group)warrants Phase III study More uniform disease characteristics
Phase III Compare new treatment with Larger than Phase II (100s ofstandard patients/treatment group)
Support marketing approval Same tumor type Broader patient pool
Phase IV Integrate clinical study experience Very large cohorts (100s-1000s)into general clinical practice Represent general patient Monitor safety after approval population
ONCOLOGYDrug development
Clinical evaluation of cytotoxic agents
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ONCOLOGYDrug development
Response rate
Survival
Disease-free survival
Time to disease progression
Duration of response
Quality of life
Pharmacoeconomics
Clinical trials: Efficacy endpoints
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Adapted from World Health Organization, 1980.
Clinical endpoints: Complete remission
ONCOLOGYDrug development
PrimaryTumor
Nodes
Metastases
Disappearance of all clinical,radiologic and biologic
signs of tumor
Treatment
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Treatment
Decrease of the multiple of twotumor diameters by at least 50%
ONCOLOGYDrug developmentClinical endpoints: Partial remission
Adapted from World Health Organization, 1980.
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Increase of the multiple of twotumor diameters by at least 25%
ONCOLOGYDrug development
Clinical endpoints: Disease progression
Adapted from World Health Organization, 1980.
Treatment
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Contraindications for Chemotherapy
A. ABSOLUTE CONTRAINDICATIONS- Terminal diseases (patients with very short life expectancy)- Pregnancy (first trimester)- Septicaemia- Coma
B. RELATIVE CONTRAINDICATION- Infants under 3 months- Old age (in particular elderly patients with slow-growing tumours with lowsensitivity to chemotherapy)
- Very low performance status (less than 40)- Severe organ failure (for certain drugs) e.g. kidney, heart, liver, bone-marrow- Brain metastases (if not treatable by radiotherapy)- Dementia- Inability of patient to attend clinic regularly- Lack of co-operation on part of patient- Tumour resistance to anticancer chemotharapy
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Osteosarcoma
Incidence : 2,1 cases/ 1000.000Peak : 10-14 yrs. : = 1,6 : 1
Goal : cure with Preoperative Chemo +Limb Sparing/Amputation + Adjuvant Chemo
Prognosis : 5 y DFS : 60%-65%Amputation alone : 5Y.S : 12%-15%Combine Modality: 5Y.S : 60%-70%
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TREATMENT NEO ADJUVANT
PREOPERATIVE CHEMOTHERAPYSURGERYADJUVANT CHEMOTHERAPYRehabilitationPsychological Support
HUVOS SYSTEM FOR HISTOLOGIC GRADING
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HUVOS SYSTEM FOR HISTOLOGIC GRADINGOf Effect of CHEMOTHERAPY on Primary OSTEOSARCOMA
Grade EffectI Little or no effect identifiedII Areas of acellular tumor osteoid,necrotic,and/or
fibrotic material attributable to the effect ofchemotherapy with other areas of histologicallyvariable tumor
III Predominant areas of acellular tumor osteoid,necrotic ,and/or fibrotic material attributableto the effect of chemotherapy,with onlyscattered foci of histologically viable tumor cellsidentified
IV No Histologic evidence of viable tumor identifiedwithin the entire specimen
From Huvos AG et al Arch.Pathol Lab Med 101:14-18,1977 with permission
THE GRADING SYSTEM FOR HISTOLOGIC RESPONSE
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THE GRADING SYSTEM FOR HISTOLOGIC RESPONSEof CHEMOTHERAPY on Primary OSTEOSARCOMA (Modified)
Grade EffectPOOR RESPONSE
I No effect identifiedII 5% to 95% viable tumor remaining
GOOD RESPONSE
III Scattered foci of viable tumor seen( < 5% of the tumor )
IV No viable tumor seen in extensive sampling(at least a full cross-section of the tumor)
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Histological Grading of Resected TumorSpecimen.
5 Years DFS by HUVOS IV : 91%
III : 72%II : 66%
I : 50%
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CELL - CYCLE NON SPECIFIC DRUGS
Efektif pada cell baik yang active dalam cell cycleataupun yang sedang resting
~ : Photon irradiation
- Class Type ObatAlkylating Nitrogen mustard Mechlorethamine
agent Nitrosurea Carmustine = BCNULomustine = CCNUSemustine = methyl CCNU
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ONCOLOGYCancer biology
Tumor growth and detection
10 12
10 9
time
Diagnosticthreshold
(1cm)
Undetectablecancer
Detectablecancer
Limit ofclinical
detection
Hostdeath
N u m
b e r o
f
c a n c e r c e
l l s
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early lateNo response to therapy10 12
1 kg
10 9
1 g
10 6
1 mg
10 3 1ug
1induction consolidation maintenance cure
clinicallydietectabtumor
long-termremission
immuneresistance host
humoral +cellular
numberof tumourcells inthe body
DIAGRAMMATIG PRESENTATION OF THE REDUCTION OF THENUMBER OF TUMOUR CELLS IN THE BODY
kecenderungan tumorberkembang
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ONCOLOGYCancer biology
Malignant tumor cells can remaindormant yet viable for years
Emergence from dormancy can leadto disease recurrence
Possible mechanisms: Cells may arrest in G 0 phase Rate of cell death counterbalances rate ofcell division
Dormancy of tumor cells
Fidler IJ. Cancer: Principles & Practice of Oncology. 5th ed. 1997;141.
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ONCOLOGYPrinciples of chemotherapy
Busulfan Cytosine Etoposide Bleomycin L-asparaginase
Carmustine Arabinoside Teniposide Dactinomycin Hydroxyurea
Chlorambucil Floxuridine Vinblastine Daunorubicin Procarbazine
Cisplatin Fluorouracil Vincristine Doxorubicin
Cyclophosphamide Mercaptopurine Vindesine Mitomycin-c
Ifosfamide Methotrexate Taxoids Mitoxantrone
Melphalan Plicamycin
AlkylatingAgents
Anti-Metabolites
MitoticInhibitors
Antibiotics Others
Classification of cytotoxic agents
ONCOLOGY
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ONCOLOGYPrinciples of chemotherapy
DNA synthesis
Antimetabolites
DNA
DNA transcription DNA duplication
Mitosis
Alkylating agents
Spindle poisons
Intercalating agentsCellular level
Action sites of cytotoxic agents
ONCOLOGY
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ONCOLOGYPrinciples of chemotherapy
6-MERCAPTOPURINE
6-THIOGUANINE
METHOTREXATE
5-FLUOROURACIL
HYDROXYUREA
CYTARABINE
PURINE SYNTHESIS PYRIMIDINE SYNTHESIS
RIBONUCLEOTIDES
DEOXYRIBONUCLEOTIDES
DNA
RNA
PROTEINS
MICROTUBULESENZYMES
L-ASPARAGINASE
VINCA ALKALOIDS
TAXOIDS
ALKYLATING AGENTS
ANTIBIOTICS
ETOPOSIDE
Action sitesof cytotoxic agents
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ONCOLOGYPrinciples of chemotherapy
CYCLOPHOSPHAMIDE
4-OH CYCLOPHOSPHAMIDE
ALDOPHOSPHAMIDE
PHOSPHORAMIDEMUSTARD
4-KETOCYCLOPHOSPHAMIDE
CARBOXYPHOSPHAMIDE
ACROLEIN
HEPATICCYTOCHROMES
P 450ACTIVATION
CYTOTOXICITYTOXICITY
INACTIVATION ALDEHYDE
DEHYDROGENASE
Cyclophosphamide
Metabolism of cytotoxic agents
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ONCOLOGYPrinciples of chemotherapy
Mucositis
Nausea/vomiting
DiarrheaCystitis
Sterility
Myalgia
Neuropathy
Alopecia
Pulmonary fibrosis
Cardiotoxicity
Local reaction
Renal failure
Myelosuppression
Phlebitis
Side effects of chemotherapy
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ONCOLOGYPatient management
Cancer patient management: Solid tumors
Therapeutic decision
Clinical findings
Cancer diagnosis
Therapeutic intention
Biopsy CT scans
Staging/Grading
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ONCOLOGYPatient management
Tumor markers:Examples
Prostatecancer
PSA
EAP
Testicularcancer
AFP, hCG
Pancreaticcancer
CA 19-9
BreastcancerCA 15-3
Ovariancancer
CA 125
Tretter C. Current Cancer Therapeutics. 1998;224-237.Rosenbaum EH. Everyones Guide to Cancer Therapy, 3rd ed. 1997;616-622.
Haskell CM. Cancer Treatment, 4th ed. 1995;322-337.Berek JS. Cancer Treatment, 4th ed. 1995;628-634.
ONCOLOGY
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ONCOLOGYPatient management
TNM classification
Tumor
Nodes
Metastasis
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ONCOLOGYPatient management
Tumor extent/staging
Localized disease= limited stage
ChemotherapyRadiotherapy
SurgeryImmunotherapy
Hormonal therapyPalliative care
Tumor extent/staging
Metastatic disease
ExtentResectable
tumorNonresectable
tumor
Operablepatient
Inoperablepatient
Surgery+ Radiation therapy+ Chemotherapy
+ Hormonal-immunotherapy
Radiation therapyChemotherapyHormonal therapyImmunotherapy
and/or
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Classification: Leukemias (NON SOLID CANCER)
ONCOLOGYPatient management
Morphology andcytochemistry (ie, lineage)
Maturational stage
Genotype
Scheinberg DA, et al. Cancer: Principles & Practice of Oncology. 5th ed. 1997;2293-2321.Deisseroth AB, et al. Cancer: Principles & Practice of Oncology. 5th ed. 1997;2321-2343.
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Staging: Lymphomas
Shipp AA, et al. Cancer: Principles & Practice of Oncology. 5th ed. 1997:2165-2220.
ONCOLOGYPatient management
Number of nodal sites involved Presence of disease above or
below diaphragm Presence or absence of
systemic symptoms Presence or absence of
extranodal disease
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Surgery in cancer
Rosenberg SA. Cancer: Principles & Practice of Oncology, 5th ed. 1997;295-306.
ONCOLOGYPatient management
Tissue acquisition for histologic disease
Primary treatment modality in localized disease(alone or in combination with other treatment modalities)
Reduction of tumor bulk Resection with intent to cure
Treatment of oncologic emergencies
Reconstruction or rehabilitation
Palliation of tumor-related symptoms
Prophylactic use in high-risk patients
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ONCOLOGYPatient management
Teletherapy (eg, orthovoltage,
supervoltage, intraoperativeradiotherapy, stereotaxic radiosurgery)
Brachytherapy (eg, internal radiationtherapy, interstitial radiation therapy,intracavitary radiation, intraluminalradiation therapy)
Radiation therapy
Hellman S. Cancer: Principles & Practice of Oncology, 5th ed. 1997;307-332.
ONCOLOGY
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ONCOLOGYPatient management
Chemotherapy
Cytotoxic agent Hormonal therapy
Biologic therapy
Systemic therapies
Haskell CM. Cancer Treatment. 4th ed. 1995;31-56.
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Pola Sensititivitas Kanker terhadap Sitostatika--------------------------------------------------------------------------------------------------------Kelompok I : Kanker dengan sitostatika mutakhir menghasilkan efek
sitoreduktif yang cepat dan kesembuhan umumnya terjadipada kanker yang secara intrinsik sensitif terhadap kemoterapisitostatika (contohnya: leukemia limfoblastik akut pada anakanak, penyakit Hodgkin, beberapa jenis limfoma non-Hodgkin,kanker testis, dan lain lain).
Kelompok II : Kanker yang biasanya berespon baik pada saat permulaandiberikan sitostatika namun kemudian sering berubahmenjadi refrakter` terhadap sitostika berikutnya (contohnya:kanker payudara, kanker paru sel kecil, kanker ovarium yangkambuh, dan lain lain).
Kelompok III : Tumor yang secara intrinsik resisten terhadap hampir semuakemoterapi sitostatika (contohnya: melanoma maligna,kanker colon, dan lain lain)
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Problems of Schedules in CombinationChemotherapy
Choice of drug used in combinations :(a) empirical basis :
- drugs most effective in a tumour type, whenused alone
- no cross resistance, different mechanism ofaction
- toxicity spectrum of drugs differing from eachother : no additive toxicity
(b) information from animal models : gives little directinformation
ONCOLOGY
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ONCOLOGYPrinciples of chemotherapy
INCREASED EFFICACY
Different mechanisms of action Compatible side effectsDifferent mechanisms of resistance
ACTIVITY SAFETY
Aim of combination therapy
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Theoritical Basis for the Effect ofCombination Chemotherapy
Cell Kinetic Factors
1. Drugs with differing toxicities to host tissues and different mechanism of actionmay, when used in combinations :(a) increase tumour-cell kill without a corresponding increase in host
toxicity :improved preferential killing
(b) allow fore more rapid host recovery and better selectivity :more rapid preferential killing
(c) kill various segment of neoplastic cells in different phases of the cycle :more complete remissions , delay of resistant cell
populations
2. Additive toxicity to host tissues without additive tumour-cell kill results indecreas ed effectiveness of combinations, or oven preferential killing of normalhost cell
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Factors to be Considered in the Planning of Chemotherapy
A. FACTOR TO BE CONSIDERED IN THE PLANNING OF CHEMOTHERAPY- Choice of drug
- Dose- Route- Schedule- Single or combination- Sequence
B. FACTOR RELATED TO THE PATIENT- Age, sex- Socio-economic status- Nutritional status- Performance status- Bone-marrow reserve- Pulmonary, renal, hepatic and cardiac function- Associated diseases
- Possible individual drug metabolismC. FACTORS RELATED TO THE TUMOUR- Histology, histological subtypes, grading- Primary or metastatic- Site of metastases- Dimension of tumour mass (if possible cell kinetic characteristics)- Presence of effusion (possible reservoir of drug activity)
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Factors to be Considered in the Planning of Chemotherapy
A. FACTOR TO BE CONSIDERED IN THE PLANNING OFCHEMOTHERAPY- Choice of drug- Dose- Route
- Schedule- Single or combination- Sequence
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Factors to be Considered in the Planning of Chemotherapy
B. FACTOR RELATED TO THE PATIENT- Age, sex- Socio-economic status- Nutritional status
- Performance status- Bone-marrow reserve- Pulmonary, renal, hepatic and cardiac function- Associated diseases- Possible individual drug metabolism
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Factors to be Considered in the Planning of Chemotherapy
C. FACTORS RELATED TO THE TUMOUR- Histology, histological subtypes, grading- Primary or metastatic- Site of metastases- Dimension of tumour mass (if possible cellkinetic characteristics)- Presence of effusion (possible reservoir of drugactivity)
ONCOLOGY
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ONCOLOGYPatient management
Performance status scalesCorrespondence between ECOG and Karnofsky scales
Grade Criteria (simplified) % Functional status
0 Normal activity 100 Able to carry on normal activity;no special care is needed
90
1 Symptoms but ambulatory 80
70 Unable to work; able to live at home;cares for most personal needs;a varying amount of assistance is needed
2 In bed 50% of time 40 Unable to care for self; requiresequivalent of institutional or hospital
30 care; disease may be progressing rapidly
4 100% bedridden 2010
5 Dead 0 Dead
ECOG KARNOFSKY
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TAX 323/EORTC TAX 323/Q of L TAX 324/Dana Farber TAX GORTEC 2000 01
Clinical Trials
in Head & Neck Cancer
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TAX 323/EORTC
Neck dissection
InoperableSCCHNStage 3/4
Stratification:1 tumour site
Institution
Taxotere (75 mg/m)Cisplatin (75 mg/m)
5-FU (750 mg/m/dx5)
TCF arm:
Q 3 weeks x 4 cycles
Cisplatin (100 mg/m)5-FU (1000 mg/m/dx5)
CF arm:
Q 3 weeks x 4 cycles
Radiotherapy(~70 Gy over
7 weeks)Follow-up
Surgery for residualdisease
R
Eva Remenar et al. ASCO 2006, abstract 5516.Jacques Bernier et al. ASCO 2006, abstract 5522.
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Primary objective PFS (Progression free survival)
Secondary objectives Response after chemotherapy and overall
Local symptoms Duration of response Time to treatment failure Survival Toxicity Quality of life (QOL)
TAX 323/EORTC: Study objectives PFS = Progression freesurvival
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PF (n=181)N (%)
TPF (n=177)N (%)
Performance status(EGOC)
01
91 (50.3)90 (49.7)
90 (50.8)86 (48.6)
Median age (years,range)
53 (30 71) 53 (31 70)
GenderMaleFemale
162 (89.5)19 (10.5)
159 (89.8)18 (10.2)
TAX 323/EORTC: Patient characteristics
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PF (n=181)N (%)
TPF (n=177)N (%)
Primary tumour siteOral cavityOropharynxHypopharynxLarynx
32 (17.7)84 (46.4)52 (28.7)13 (7.2)
31 (17.5)81 (45.8)53 (29.9)12 (6.8)
Tumour grading
Grade 1 + 2Grade 3 = 4U + X
122 (64.7)31 (17.1)28 (15.4)
111 (62.7)40 (22.5)26 (14.7)
TAX 323/EORTC: Patient/tumour characteristics
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TAX 323/EORTC: Progression-free survival
Median: 12.7 months (10.2 14.2)
Median: 8.4 months (95% CI: 7.5 9.6)
Years
0 1 2 3 4 5 0
20
40
60
80
100 Cox model (primary): p=0.006Hazard ratio=0.7295% CI (0.56 0.91)Unadjusted log-rank test: p=0.006
Randomisedarm
CF
TCF
PFS = Progression free
survival
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TAX 323/EORTC: Overall survival
Eva Remenar et al.,ASCO 2006,abstract 5516
P r o
b a
b i l i t y
( % )
CF TCF
Mean survival 14.2 m 18.6 m
Hazard ratio 0.73 [0.56 0.90]
p-value 0.0052
010
20
30405060
708090
100
0 6 12
18
24
30
36
42
48 54
Months
60
66
72
TCFCF
Phase III
OS = Overall
survival
Survival from high grade localised osteosarcoma: combined
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Survival from high grade localised osteosarcoma: combinedresult and prognostic factors from three European
Osteosarcoma Intergroup RCT (Whelan,et al. Annals of Oncology 23:1607-16,2012)
- 1067 pts with localised extremity osteosarcoma 3 RCT- Standard treatment : Doxorubicin 75mg/m 2 and Cisplastin 100
mg/m 2
- Comparators :- Add of MTX (BO02/80831)- Multidrug regimen (BO03/80861)- Dose intense schedule (BO06/80931)
Standard protocols
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Treatment Protocols by Trial
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Pattern of recurrence
OS = Overall survival
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Survival
Overall survival : 5-years: 56% (95% CI 53-59%) 10-years: 52% (95% CI 49-55%)
Progression Free Survival : 5-years: 43% (95% CI 40-46%) 10-years: 42% (95% CI 39-46%)
No difference of survival between trials /treatment arms
PFS = Progression free
survival
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Osteosarcoma ChemotherapyProtocols
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Neoadjuvant chemotherapy for osteosarcoma of theextremities with metastases at presentation: recent experience
at the Rizzoli Institute in 57 patients treated with cisplatin,doxorubicin, and a high dose of methotrexate and ifosfamide
(Bacci G, et al. Annals of Oncology 14:1126-34, 2003)
Patients < 40 yo, with newly diagnosed HGOE with metastases atpresentation
New protocol therapy higher dose in Ifosfamide and MTX Site of metastases :
Lung 43 pts Bone 3 pts Lung and bone 9 pts Lymph node 2 pts
Neoadjuvantchemotherapy
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Results
Primary tumor Clinical and radiological response to
chemotherapy 79% Histological response of the primary tumor:
Good (54%) , Poor (46%)
Bacci G, et al. Neoadjuvant chemotherapy for osteosarcoma of the extremities with metastases at presentation: recent experience at the Rizzoli Institute in 57 patientstreated with cisplatin, doxorubicin, and a high dose of methotrexate and ifosfamide. Annals of Oncology 14:1126-34, 2003
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Results Metastases response to chemotherapy
Type of response Metastases Response
Radiologicalresponse
- Lung only (43 pts) - Complete : 5 pts- Partial : 10 pts
- Stable : 26 pts- Mixed : 2 pts
Radiologicalresponse
- Bone only (3 pts)- Bone and lung (9 pts)
- Stable : 8 pts- Progressive : 4 pts
Surgical treatmentand histologicalreponse
140 resected metastases in the26 patients with pulmonarynodules
- Good : 53%- Poor : 46%
Bacci G, et al. Neoadjuvant chemotherapy for osteosarcoma of the extremities with metastases at presentation: recent experience at the Rizzoli Institute in 57 patients
treated with cisplatin, doxorubicin, and a high dose of methotrexate and ifosfamide. Annals of Oncology 14:1126-34, 2003
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Outcomes
Bacci G, et al. Neoadjuvant chemotherapy for osteosarcoma of the extremities with metastases at presentation: recent experience at the Rizzoli Institute in 57 patientstreated with cisplatin, doxorubicin, and a high dose of methotrexate and ifosfamide. Annals of Oncology 14:1126-34, 2003
EFS = Event free survival
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Terapi Suportif pd Manajemen Kanker
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Terapi Suportif pd Manajemen Kanker
Tujuan pengobatankanker tercapai:
kuratif: sembuh /disease free survival >
paliatif: keluhankomplikasi kanker (-)/
-
8/10/2019 Farmakologi Anti Kanker
71/75
SyAnti cancer drugs setting
Primary chemotherapy Neo adjuvant setting Induction therapy (pre-
main modality th/)
Adjuvant setting (post-main modality th/) Chemo-radiation:
- chemotherapy as as radiosensitizer- concomitant / concurrent chemo-radiation- sandwich chemoradiation
Sequential setting
-
8/10/2019 Farmakologi Anti Kanker
72/75
-
8/10/2019 Farmakologi Anti Kanker
73/75
Surgery
Radiation +Chemotherapy asRadiosensitizer
AdjuvantChemotherapy
Adjuvant Therapy ofMusculoskeletal Tumors:
-Early / locally stage
-
8/10/2019 Farmakologi Anti Kanker
74/75
Surgery Chemotherapypost surgery
Sequential Therapy of
Neoadjuvantchemotherapy
Locally advancedstageBulky tumors
-
8/10/2019 Farmakologi Anti Kanker
75/75
TERIMA KASIH
TERIMA KASIH
TERIMA KASIH
TERIMA KASIHTERIMA KASIH