FARMAKOLOGI

OBAT ANTI KANKER

PSFKKO
Universitas Gadjah Mada
2014

* CELL - CYCLE SPECIFIC DRUGS : = phase non specific

Paling efektif jika cell tersebut aktif dalam
cell cycle
- Class
Alkylating
agent

Type
Nitrogen mustard
Alkyl sulfonate
Triazine DTIC
Metal salt

Natural product Antibiotic

Obat
Chlorambucil, cyclophosphamide
Melphalan
Busulfan

Cisplatin
Actinomycin -D
Daunorubicin
Doxorubicin

ONCOLOGY
Drug development
Steps in cancer drug development

Identify Candidate Compounds

Screening
Preclinical Evaluation
Production and Formulation
Toxicology

Pharmacology

Phase I, II, III, IV Clinical Trials

General Medical Practice

Biochemistry

Procedure for the Development, Testing and Use of Chemotherapeutic Drugs

Drugs Development
Random Screening

Logical Design

Animal Data
Formulation
Phase 1 Trials (Toxicity maximum tolerated
dose)

Phase 2 Trials (Efficacy in different tumours)

Phase 3 Trials (Comparative Randomized
studies)

Clinically Useful New Agent

Use As
Adjuvant If
Circumstances Exist

Combine With Other

Active Agent In
Advanced Disease

ONCOLOGY
Drug 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.

ONCOLOGY
Drug development
Identification of candidate compounds: Molecular-targeted screening

Computer-aided construction of
molecules
Mutant oncogenes (BCR-ABL)
Aberrant tumor suppressor genes (RB)
Protein kinases

Transcription activators

Grever MR, Chabner BA. Cancer: Principles & Practice of Oncology. 1997;385-394.

ONCOLOGY
Drug development
Screening for anticancer activity

IN VITRO HUMAN TUMOR CELL LINE PANELS

Lung

Colon

Breast

Nonspecific antitumor activity

CNS

Melanoma

Ovarian

Prostate

Highly specific antitumor activity

In Vivo tumor panel

human tumor xenograft studies

Targeted preclinical development

Preclinical development
followed by broad-based clinical trials

Specific disease-oriented
Phase I/II trials

Adapted from NCI drug screening strategy,1985.

ONCOLOGY
Drug development
Preclinical evaluation of cytotoxic agents

IN VITRO

IN VIVO

Mechanism of action

Stage I

Stage II

Target level

Maximum tolerated dose Spectrum of activity

Cellular level

Dose-limiting toxicities

Schedule dependency

Efficacy

Route administration
Cross resistance
Combination therapies

ONCOLOGY
Drug development
Use of animal models in evaluation of cytotoxic agents

Preclinical studies in mice, rats,

and dogs provide an important
bridge from in vitro studies to
clinical studies
Objectives
Define major toxicities
Identify initial safe starting dose
for clinical trials

ONCOLOGY
Drug development
Clinical evaluation of cytotoxic agents
Study Phase

Objectives

Patient Population

Phase I

Identify maximum tolerated dose

Small (3-6 patients/dose level)

Define key toxicities

Various tumor types

Evaluate tumor response

Larger than Phase I (10-50

Determine whether drug

patients/treatment group)
More uniform disease characteristics

Phase II

warrants Phase III study

Phase III

Phase IV

Compare new treatment with

Larger than Phase II (100s of

standard
Support marketing approval

patients/treatment group)
Same tumor type
Broader patient pool

Integrate clinical study experience

Very large cohorts (100s-1000s)

into general clinical practice

Monitor safety after approval

Represent general patient

population

ONCOLOGY
Drug development
Clinical trials: Efficacy endpoints

Response rate
Survival
Disease-free survival
Time to disease progression
Duration of response

Quality of life
Pharmacoeconomics

ONCOLOGY
Drug development
Clinical endpoints: Complete remission

Primary
Tumor
Nodes

Treatment

Metastases

Disappearance of all clinical,

radiologic and biologic
signs of tumor
Adapted from World Health Organization, 1980.

ONCOLOGY
Drug development
Clinical endpoints: Partial remission

Treatment

Decrease of the multiple of two

tumor diameters by at least 50%
Adapted from World Health Organization, 1980.

ONCOLOGY
Drug development
Clinical endpoints: Disease progression

Treatment

Increase of the multiple of two

tumor diameters by at least 25%
Adapted from World Health Organization, 1980.

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 low
sensitivity 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

Osteosarcoma
Incidence : 2,1 cases/ 1000.000
Peak : 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%

TREATMENT NEO ADJUVANT

PREOPERATIVE CHEMOTHERAPY
SURGERY
ADJUVANT CHEMOTHERAPY
Rehabilitation
Psychological Support

HUVOS SYSTEM FOR HISTOLOGIC GRADING

Of Effect of CHEMOTHERAPY on Primary OSTEOSARCOMA

Grade
I
II

III

IV

Effect

Little or no effect identified

Areas of acellular tumor osteoid,necrotic,and/or
fibrotic material attributable to the effect of
chemotherapy with other areas of histologically
variable tumor
Predominant areas of acellular tumor osteoid,
necrotic ,and/or fibrotic material attributable
to the effect of chemotherapy,with only
scattered foci of histologically viable tumor cells
identified
No Histologic evidence of viable tumor identified
within the entire specimen

From Huvos AG et al Arch.Pathol Lab Med 101:14-18,1977 with permission

THE GRADING SYSTEM FOR HISTOLOGIC RESPONSE

of CHEMOTHERAPY on Primary OSTEOSARCOMA (Modified)

Grade

Effect

POOR RESPONSE
I
II

No effect identified
5% to 95% viable tumor remaining

GOOD RESPONSE
III
IV

Scattered foci of viable tumor seen

( < 5% of the tumor )
No viable tumor seen in extensive sampling
(at least a full cross-section of the tumor)

Histological Grading of Resected Tumor

Specimen.
5 Years DFS by HUVOS IV : 91%
III : 72%
II : 66%
I : 50%

CELL - CYCLE NON SPECIFIC DRUGS

Efektif pada cell baik yang active dalam cell cycle
ataupun yang sedang resting
~ : Photon irradiation

- Class
Type
Alkylating
Nitrogen mustard
agent Nitrosurea Carmustine = BCNU

Obat
Mechlorethamine
Lomustine = CCNU
Semustine = methyl CCNU

ONCOLOGY
Cancer biology
Tumor growth and detection

Number of
cancer cells

1012

Diagnostic
threshold
(1cm)

109

time
Undetectable
cancer

Detectable
cancer

Limit of
clinical
detection

Host
death

DIAGRAMMATIG PRESENTATION OF THE REDUCTION OF THE

NUMBER OF TUMOUR CELLS IN THE BODY
number
of tumour
cells in
the body

1012

No response to therapy

early

1 kg

late

kecenderungan tumor
berkembang

clinically
dietectab
tumor

109
1g

long-term
remission

106

immune
resistance host

1 mg

humoral +
cellular

103
1ug

1
induction

consolidation

maintenance

cure

ONCOLOGY
Cancer biology
Dormancy of tumor cells
Malignant tumor cells can remain
dormant yet viable for years
Emergence from dormancy can lead
to disease recurrence
Possible mechanisms:
Cells may arrest in G0 phase
Rate of cell death counterbalances rate of
cell division

Fidler IJ. Cancer: Principles & Practice of Oncology. 5th ed. 1997;141.

ONCOLOGY
Principles of chemotherapy
Classification of cytotoxic agents
Alkylating
Agents

AntiMetabolites

Mitotic
Inhibitors

Antibiotics

Others

L-asparaginase

Busulfan

Cytosine

Etoposide

Bleomycin

Carmustine

Arabinoside

Teniposide

Dactinomycin Hydroxyurea

Chlorambucil

Floxuridine

Vinblastine

Daunorubicin Procarbazine

Cisplatin

Fluorouracil

Vincristine

Doxorubicin

Cyclophosphamide Mercaptopurine Vindesine

Mitomycin-c

Ifosfamide

Mitoxantrone

Melphalan

Methotrexate

Taxoids

Plicamycin

ONCOLOGY
Principles of chemotherapy
Action sites of cytotoxic agents
DNA synthesis
Antimetabolites

DNA

DNA transcription

Alkylating agents

DNA duplication
Mitosis

Cellular level

Intercalating agents
Spindle poisons

ONCOLOGY
Principles of chemotherapy
Action sites
of cytotoxic agents
PURINE SYNTHESIS

PYRIMIDINE SYNTHESIS

6-MERCAPTOPURINE

6-THIOGUANINE

RIBONUCLEOTIDES

METHOTREXATE
5-FLUOROURACIL
HYDROXYUREA
DEOXYRIBONUCLEOTIDES

CYTARABINE

ALKYLATING AGENTS
ANTIBIOTICS

DNA

ETOPOSIDE

RNA

PROTEINS

L-ASPARAGINASE
VINCA ALKALOIDS

ENZYMES

MICROTUBULES

TAXOIDS

ONCOLOGY
Principles of chemotherapy

Metabolism of cytotoxic agents

CYCLOPHOSPHAMIDE

Cyclophosphamide

HEPATIC
CYTOCHROMES
P 450

ACTIVATION

INACTIVATION
4-KETOCYCLOPHOSPHAMIDE
CARBOXYPHOSPHAMIDE

ALDEHYDE

4-OH CYCLOPHOSPHAMIDE

DEHYDROGENASE

ALDOPHOSPHAMIDE

ACROLEIN

PHOSPHORAMIDE
MUSTARD

TOXICITY

CYTOTOXICITY

ONCOLOGY
Principles of chemotherapy
Side effects of chemotherapy
Mucositis
Nausea/vomiting
Diarrhea

Cystitis

Alopecia

Pulmonary fibrosis

Cardiotoxicity
Local reaction

Sterility
Myalgia
Neuropathy

Renal failure

Myelosuppression
Phlebitis

ONCOLOGY
Patient management
Cancer patient management: Solid tumors
Clinical findings

Biopsy

Cancer diagnosis

Staging/Grading

Therapeutic intention

Therapeutic decision

CT scans

ONCOLOGY
Patient management
Tumor markers:
Examples
Prostate
cancer
PSA
EAP

Pancreatic
cancer
CA 19-9

Breast
cancer
CA 15-3

Ovarian
cancer
CA 125

Testicular
cancer
AFP, hCG

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
Patient management
TNM classification

Tumor

Nodes
Metastasis

ONCOLOGY
Patient management
Tumor extent/staging
Tumor extent/staging

Metastatic disease

Extent

Chemotherapy
Radiotherapy
Surgery
Immunotherapy
Hormonal therapy
Palliative care

Localized disease
= limited stage
Resectable
tumor
Operable
patient

Surgery
+ Radiation therapy
+ Chemotherapy
+ Hormonal-immunotherapy

Nonresectable
tumor
Inoperable
patient

Radiation therapy
Chemotherapy
and/or
Hormonal therapy
Immunotherapy

ONCOLOGY
Patient management
Classification: Leukemias (NON SOLID CANCER)

Morphology and
cytochemistry (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.

ONCOLOGY
Patient management
Staging: Lymphomas

Number of nodal sites involved

Presence of disease above or
below diaphragm
Presence or absence of
systemic symptoms
Presence or absence of
extranodal disease

Shipp AA, et al. Cancer: Principles & Practice of Oncology. 5th ed. 1997:2165-2220.

ONCOLOGY
Patient management
Surgery in cancer

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

Rosenberg SA. Cancer: Principles & Practice of Oncology, 5th ed. 1997;295-306.

ONCOLOGY
Patient management
Radiation therapy

Teletherapy (eg, orthovoltage,

supervoltage, intraoperative
radiotherapy, stereotaxic radiosurgery)
Brachytherapy (eg, internal radiation
therapy, interstitial radiation therapy,
intracavitary radiation, intraluminal
radiation therapy)
Hellman S. Cancer: Principles & Practice of Oncology, 5th ed. 1997;307-332.

ONCOLOGY
Patient management
Systemic therapies

Chemotherapy

Cytotoxic agent
Hormonal therapy

Biologic therapy

Haskell CM. Cancer Treatment. 4th ed. 1995;31-56.

Pola Sensititivitas Kanker terhadap Sitostatika

-------------------------------------------------------------------------------------------------------Kelompok I :
Kanker dengan sitostatika mutakhir menghasilkan efek
sitoreduktif yang cepat dan kesembuhan umumnya terjadi
pada kanker yang secara intrinsik sensitif terhadap kemoterapi
sitostatika (contohnya: leukemia limfoblastik akut pada anak
anak, penyakit Hodgkin, beberapa jenis limfoma non-Hodgkin,
kanker testis, dan lain lain).
Kelompok II :

Kelompok III :

Kanker yang biasanya berespon baik pada saat permulaan

diberikan sitostatika namun kemudian sering berubah
menjadi refrakter` terhadap sitostika berikutnya (contohnya:
kanker payudara, kanker paru sel kecil, kanker ovarium yang
kambuh, dan lain lain).

Tumor yang secara intrinsik resisten terhadap hampir semua

kemoterapi sitostatika (contohnya: melanoma maligna,
kanker colon, dan lain lain)
------------------------------------------------------------------------------------------------------

Problems of Schedules in Combination

Chemotherapy

Choice of drug used in combinations :

(a) empirical basis :
- drugs most effective in a tumour type, when
used alone
- no cross resistance, different mechanism of
action
- toxicity spectrum of drugs differing from each
other : no additive toxicity
(b) information from animal models : gives little direct
information

ONCOLOGY
Principles of chemotherapy
Aim of combination therapy

INCREASED EFFICACY

ACTIVITY
Different mechanisms of action
Different mechanisms of resistance

SAFETY
Compatible side effects

Theoritical Basis for the Effect of

Combination Chemotherapy
Cell Kinetic Factors
1.

Drugs with differing toxicities to host tissues and different mechanism of action
may, 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 in

decreas ed effectiveness of combinations, or oven preferential killing of normal
host cell

Factors to be Considered in the Planning of Chemotherapy

A.

B.

C.

FACTOR TO BE CONSIDERED IN THE PLANNING OF CHEMOTHERAPY

- Choice of drug
- Dose
- Route
- Schedule
- Single or combination
- Sequence
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
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)

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

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

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 cell
kinetic characteristics)
- Presence of effusion (possible reservoir of drug
activity)

ONCOLOGY
Patient management
Performance status scales
Correspondence between ECOG and Karnofsky scales
ECOG
Grade
0

Criteria (simplified)
Normal activity

KARNOFSKY
%
100
90

Symptoms but ambulatory

In bed <50% of time

60
50

In bed >50% of time

40
30

100% bedridden

Dead

Able to carry on normal activity;

no special care is needed

80
70

Functional status

Unable to work; able to live at home;

cares for most personal needs;
a varying amount of assistance is needed

Unable to care for self; requires

equivalent of institutional or hospital
care; disease may be progressing rapidly

20
10
0

Dead

Clinical Trials
in Head & Neck Cancer
TAX 323/EORTC
TAX 323/Q of L
TAX 324/Dana Farber
TAX GORTEC 200001

TAX 323/EORTC
Neck dissection

Inoperable
SCCHN
Stage 3/4
Stratification:
1 tumour site
Institution

TCF arm:
Taxotere (75 mg/m)
Cisplatin (75 mg/m)
5-FU (750 mg/m/dx5)
Q 3 weeks x 4 cycles

R
CF arm:
Cisplatin (100 mg/m)
5-FU (1000 mg/m/dx5)
Q 3 weeks x 4 cycles

Eva Remenar et al. ASCO 2006, abstract 5516.

Jacques Bernier et al. ASCO 2006, abstract 5522.

Surgery for residual

disease

Radiotherapy
(~70 Gy over
7 weeks)

Follow-up

PFS = Progression free

TAX 323/EORTC: Study objectives
survival
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: Patient characteristics

Performance status
(EGOC)
0
1
Median age (years,
range)

Gender
Male
Female

PF (n=181)
N (%)

TPF (n=177)
N (%)

91 (50.3)
90 (49.7)

90 (50.8)
86 (48.6)

53 (3071)

162 (89.5)
19 (10.5)

53 (3170)

159 (89.8)
18 (10.2)

TAX 323/EORTC: Patient/tumour characteristics

PF (n=181)
N (%)

TPF (n=177)
N (%)

Primary tumour site

Oral cavity
Oropharynx
Hypopharynx
Larynx

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 + 2
Grade 3 = 4
U+X

122 (64.7)
31 (17.1)
28 (15.4)

111 (62.7)
40 (22.5)
26 (14.7)

TAX 323/EORTC: Progression-free survival

PFS = Progression free
survival

100

Cox model (primary): p=0.006

Hazard ratio=0.72
95% CI (0.560.91)
Unadjusted log-rank test: p=0.006

80
60

Median: 12.7 months (10.214.2)

40

Randomised
arm

CF

20

TCF

Median: 8.4 months (95% CI: 7.59.6)

0
0

Years

TAX 323/EORTC: Overall survival

OS = Overall
survival

Probability (%)

Phase III
100
90
80
70
60
50
40
30
20
10
0

Mean survival
Hazard ratio

p-value

TCF
CF
0

1
2

1
8

2
4

3
0

3
6

4
2

48

Months

Eva Remenar et al.,ASCO 2006,abstract 5516

5
4

6
0

6
6

7
2

CF

TCF

14.2 m

18.6 m

0.73 [0.560.90]

0.0052

Survival from high grade localised osteosarcoma: combined

result 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/m2 and Cisplastin 100
mg/m2
- Comparators :
- Add of MTX (BO02/80831)
- Multidrug regimen (BO03/80861)
- Dose intense schedule (BO06/80931)
Standard protocols

Treatment Protocols by Trial

Pattern of recurrence

OS = Overall survival

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

Osteosarcoma Chemotherapy
Protocols

Salvage therapy
Ifosfamide 3000 mg/m2 (d1-4) with mesna
uroprotection
Etoposide 75 mg/m2 (d1-4)

To be repeated every 3-4 weeks (2 courses)

Standard regimens:
Baxter 15th ed, 2010

Salvage regimens

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
(Bacci G, et al. Annals of Oncology 14:1126-34, 2003)

Neoadjuvant
chemotherapy
Patients < 40 yo, with newly diagnosed HGOE with metastases at
presentation
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

Treatment protocol

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

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 patients
treated with cisplatin, doxorubicin, and a high dose of methotrexate and ifosfamide. Annals of Oncology 14:1126-34, 2003

Results
Metastases response to chemotherapy
Type of response

Metastases

Response

Radiological
response

- Lung only (43 pts)

Complete : 5 pts
Partial : 10 pts
Stable : 26 pts
Mixed : 2 pts

Radiological
response

- Bone only (3 pts)

- Bone and lung (9 pts)

- Stable : 8 pts
- Progressive : 4 pts

Surgical treatment
and histological
reponse

140 resected metastases in the - Good : 53%

26 patients with pulmonary
- Poor : 46%
nodules

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

Outcomes

EFS = Event free survival

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

Bentuk Pengobatan Kanker

Modalitas Utama

Terapi Suportif

- Pembedahan
- Radiasi
- Terapi sistemik kanker

Untuk mendukung
keberhasilan modalitas
utama pengobatan:
- yg bertujuan kuratif
- yg bertujuan paliatif
- yg bertujuan end of life /
hospice care

dgn obat anti kanker

(kemoterapi, terapi
target, terapi hormon,
terapi biologik)

Terapi Suportif pd Manajemen Kanker

Modalitas Utama:
Pembedahan
Radiasi
Terapi Sistemik

Terapi
SUPORTIF

Tujuan pengobatan
kanker tercapai:
kuratif: sembuh /
disease free survival >
paliatif: keluhan
komplikasi kanker (-)/
<<<<
end of life or
hospice management
(prediksi bertahan
hidup < 6 months)

SyAnti cancer drugs setting

Primary chemotherapy
Neo adjuvant setting Induction therapy (premain modality th/)
Adjuvant setting (post-main modality th/)
Chemo-radiation:
- chemotherapy as as radiosensitizer
- concomitant / concurrent chemo-radiation
- sandwich chemoradiation
Sequential setting

Solid tumors
1. Early stage:
Adjuvant
2. Locally advance/ Bulky tumors:
Neoadjuvant
3. Metastatic / Recurrence:
First line
Maintenance
Second line
Third line

Adjuvant Therapy of
Musculoskeletal Tumors:
-Early / locally stage

Surgery

Adjuvant
Chemotherapy

Radiation +
Chemotherapy as
Radiosensitizer

Sequential Therapy of

Neoadjuvant
chemotherapy
Locally advanced
stage
Bulky tumors

Surgery

Chemotherapy
post surgery

TERIMA KASIH
TERIMA KASIH
TERIMA KASIH
TERIMA KASIH
TERIMA KASIH