Medical Team (teamwork) Standard Facility Standard Protocol

Medical Record

Patient

Better Communication Unity of work rhythm

Minimal mistakeMaximal patient service

MANAGEMENT OF CANCER PATIENT

Patient Doctor

Other doctors (consultant)

Cytopathologist

Radiologist

Laboratory

MANAGEMENT OF CANCER PATIENT

diagnose and treatment patient depend on one clinician only

The Relative Frequency of Head & Neck CarcinomaThe Relative Frequency of Head & Neck Carcinoma

Nasal sinuses (4%)

Oral Cavity (55%)

Larynx (25%)Hypopharynx (5%)

Oropharynx (10%)

Nasopharynx (1%)

(Skeel RT,et.al 2000)

TERAPI DENGAN BAHAN KIMIA (HORMON/SITOSTATIKA) YANG DAPAT MENGHAMBAT PERTUMBUHAN SEL KANKER

ADJUVANT setelah operasiNEOADJUVANT sebelum radiasi atau operasiPRIORITAS UTAMARADIOSENSITIZER sebelum atau bersamaan radiasi

1. Mencapai kesembuhan ( kuratif =CURE )2. Mencapai masa bebas penyakit (DFI) yang lebih lama3. Memperbaiki kualitas hidup (SURVIVAL)4. Memperkecil masa tumor sebelum operasi (neoadjuvant) mempermudah operasi

KANKER KELENJAR

(LIMFOMA MALIGNA)

KEMOTERAPIPRIORITAS UTAMA(tanpa harus operasi)

KURATIF

PROBLEM PENANGANAN

Bedah : deformitas & fungsi kosmetik Radiasi : ES (xerostomia, mucositis/stomatitis, disfagi, nekrosis, infeksi) disfungsi

Kemoterapi : ES (mucositis/stomatitis,infeksi)

PEMEILIHAN TERAPI HARUSMEMPERTIMBANGKAN KOMPLIKASI DARI

SETIAP MODAL TERAPI

Oncology aspect

Patients & family aspect

Outcome & Side Effect Monitoring

Oncology Aspect

Diagnose:- pathology :* morphologic class : adenoCa ? * histologic grade * pattern of invasion - tumor biology ? : CD20, Bcl2, p53

c-KIT(CD117), EGFR 1, Her2, EBV ?, IgA

Diagnose: Clinical Staging

Medical Status: Risk group - Anamnesa (co-morbid) - Physic, Laboratory, ECG, Radiology - Performance status (Karnosfky-ECOG)

Mechanism chemotherapy in cellular level Reduction of tumor after Chemotherapy Rational , patient financial ?

Cell Cycle mechanism

Doubling Time

Check point controle mechanism

Target of Actions of drugs( Phase specificity ? / Non phase ?)

2.Tumor cell Apoptosis

Mechanisme of Actions

Mitochondrial pathway (Bcl2 family,p53)

Death receptor pathway (Fas-FasL, caspase family of protein)

1.Tumor cell proliferation

( influence on the response to chemotherapy )

MG2

G1S

Bleomycin

5 Fudrara C6-Hydroxyurea

5 FUMETHOTREXATE

6-Thioguanine

6-Marcaptopurine

Mytomycin

Actinomycin D

Hydrocortisone Chalones

5 FU

VinblastineVincristineColchicineGriseofulvin

Differentiation

Phleomycin

Cyclophosphamide

Purin antagonis

Hydroxy urea

Actinomycin

Cyclophosphamide

5 Fudr .5FU, Ara C. Mitomycin,Doxorubicin Thioguanine

18-30h6-20h

0,5-1h

0.5-1h

2-10h

Doxorubicin

Alkylating agent, Antimetabolic, Mitotic inhibitor, Antibiotic

No response Early recurrence Late recurrence

Tumor detectable(clinically)

Long-term Remission Not palpable

Immune resistanceof host

(humoral&cellular)

Induction Consolidation Maintenance Cure

1012

109

106

103

(1kg)

(1 g)

(1 mg)

Number ofTumor cell

Tumor invisible(Remission)

(1 úg)

Patients & family Aspect

Information about : - indication chemotherapy - regimen & cycle of Chx - Side effect of drug - living with chemotherapy - informed consent

Outcome & Side Effect Monitoring Aspect

SurvivalObjective & Subjective Outcome

Diagnose & management

Outcome Side Effect

1. Onset of SE : - Immediately ( < 1 Hour post Chemotx) Anaphylaxsis - early (1- 48 hours ) Nausea-Vomiting profuse - delayed (2 days -2 months ) leucopenia - Late (after 2 months ) myopathy, neuropathy

2.Organ Target : CNS, Cardiovascular, Respiratory, Gastroentestinal System

3.Level/degree of SE (IUCC,WHO, ECOG) : - grade 0-2 : tolerable ( safety enough ) - grade 3 (severe) : must be alert (Yellow light), need treatment ± - grade 4 (life threatening) : Hazard, early and adequate treatment

DIAGNOSE of Side Effect

PHARMACOLOGYWhen Side effect become: NADIR point (degree of SE)Onset of SE, Specificity of organ target

MANAGEMENT of Side Effect

Anticipation & PreventionDose related side effect monitoringEarly treatment of side effect

SIDE EFFECT MONITORING

PROFILE EPISODE of FEBRIL NEUTROPENI SELAMA KEMOTERAPI

Chemotherapy day

Chemotherapy day

nadir1 6 11 16 21 26

Hiperpigmentation (Fluorouracili )

Emetogenic potency of cytostatic drugs

• Weak :• mitomycin, mitoxantron, ifosfamid, 5 FU,

bleomycin,etoposide,melphalan, gemcitabin• Moderate :

cyclophosphamide,anthracyclines,cytarabin,carboplatin,taxanes,irinotecan,topotecan

• Strong : cisplatin,dacarbazine,dactinomycin,any high dose therapy

Management Side Effect

1. ANTIDOTUM to specific agent : - Antidotum of MTX : Calcium leucovorin, Ca Lefofolinat - Cardiomyopathy prophylaxis – Doxorubicin > 450 mg/m2 * Dexrazosane 10 mg – Doxorubicin 1 mg

2. Dose modification : - Toxicity grade 3 and 4 : decrease dose 25% - 50%

3. Supportive Drugs : - Haemopoetic GF : G-CSF, GM-SF, IL-3, Epo - Component Blood transfuse - Selective antibiotic

4. Sterile Room technology

TREATMENT of FEBRIL NEUTROPENI SELAMA KEMOTERAPI

Empiric antibacterial

Empiric antibacterial

Chemotherapy day

Chemotherapy day

nadir

G-CSFSterile room

1.Objective Response Evaluation2.Subjective Response Evaluation(3). Survival

CANCER OUTCOME of TREATMENT

OBJECTIVE RESPONSE EVALUATIONS

1. TUMOR SIZE : - Complete remission (CR) - Partial remission (PR) - No Changes (Stable Disease = St D) - Progressive Disease (PD)

2. Marker Tumour : - CEA, CA15-3, MCA Breast Ca - CEA, CA19-9 Pancreas Ca, Colorectal Ca - HCG Chorio Ca - PSA Prostat Ca

3. Objective-Qualitative : - Change of Clinical sign : Brain Ca-neurology sign

Treatment % 5-Year Survival

RT without salvage <30

RT with salvage ±40

Concurrent CT + RT 50-55

Sequential CT RT 50-55

RTCT 50-55

CT + RT CT 75

CTCT + RT >90CT = chemotherapy , RT = radiotherapy

Stage IV Nasopharyngeal Cancer:

Change in Overall Survival, 1980-2000

(Muhyi Al-Sarraf,2002)

Tepat indikasi : kemoterapi tepat dipilih berdasar titik tangkap kerjanya berdasar patogenesis kanker sehingga dapat tercapai tujuan : 1.kuratif 2.mencapai bebas penyakit (DFI) yang lebih lama 3.neoadjuvant (mengecilkan volume tumor preoperasi- down staging) 4.mempertahankan atau meningkatkan quality of life (terapi paliatif)

RINGKASAN :

Tepat cara pemberian obat : oral, IV, bolus, infusion dsb yang penting : penderita nyaman , tidak takut dan dengan kesadaran sendiri ingin melanjutkan kemoterapi Tepat monitoring efek obat : - penilaian hasil / respons terapi - kemampuan hidup (quality of life) dan - efek samping obat

Tepat jenis obat : sebaiknya lebih spesifik, selektif, mem- punyai Response rate tinggi, established, dan dapat dijangkau oleh penderita

Tepat dosis obat : sesuai Maximum Tolerated Dose ( Risk group )

RESUME :

Better Communication Unity of work rhythmMinimal mistakeMaximal patient service

Oncology aspect Patients & family aspect

Outcome & Side Effect Monitoring

Diagnose:- pathology - biology cell type ?

Diagnose: Staging

Medical Status: Risk group

Information about : - indication chemotherapy - regimen & cycle of Chx - Side effect of drug - living with chemtherapy - informed consent

SurvivalObjective & Subjective Outcome

Side Effect : Diagnose & management

RESUME :

TERIMA KASIH

Regimens of Chemotherapy

Regimen Response

Regimen Doses RR

Methotrexate 40-60 mg/m2/weekly 25-50%Bleomycin 10-30 mg/m2/weekly 15-25%Cisplatin 4-60 mg/m2/3 weeks 25%Carboplatin 360-400 mg/m2/4 weeks 25% divided in 3 daily5 FU 500-750 mg/m2/d1-5/ 15% 4 weeksAnthracyclines 50 mg/m2/3 weeks 25%Ifosfamide 2 g/m2/3-4 weeks 28-42%Taxan(P) 250 mg/m2/3 weeks 40%Gemcitabine 1250 mg/m2/d1,8/3 weeks ??

(Skeel RT,et.al 2000)