Pengobatan Kanker Paru - RS PARU Dr.HA ROTINSULU

TATALAKSANA
KANKER PARU
dr. Reza Kurniawan T., SpP
RS Paru dr. H.A. Rotinsulu
PEDOMAN TATALAKSANA
• Jenis histologi
• Derajat atau Stadium klinis penyakit
• Tampilan atau “Performace status”
• Tatalaksana komplikasi
JENIS HISTOLOGI
Staging SCLC
• Limited / Tingkatan terbatas :
- Tumor ditemukan dalam satu paru
- Penjalaran ke KGB paru yang sama.
• Extensive / Tingkatan luas :
- Tumor telah menyebar keluar dari satu
paru atau ke organ lain di luar paru
Staging NSCLC
• Kalisifikasi berdasarkan 3 komponen
prognosis:
– Tumor (T)
– Nodes (N)
– Metastasis (M)
• Saat ini: TNM versi 7 thn 2007  versi 8 thn
2015
International Association for the Study of Lung Cancer (IASLC), 2007
PERFORMANCE STATUS
KARNOFSKY
WH0
BATASAN
90 – 100
70 – 80
0
1
50 – 60
2
30 – 40
10 – 20
3
4
0 – 10
5
Aktivitas normal
Ada keluhan tapi masih akif, dapat
mengurus diri sendiri
Cukup aktif; kadang memerlukan
bantuan
Kurang aktif, perlu perawatan
Tidak dapat meninggalkan tempat tidur
Tidak sadar
PENGOBATAN KANKER PARU
• Pengobatan Standar selama ini adalah :
–
–
–
–
Pembedahan
Radioterapi
Kemoterapi
Targeted therapy
• Terapi tersebut biasanya diberikan secara kombinasi
atau Multi-modality
• Pendekatan pengobatan lain yaitu terapi pendukung
dikenal dengan BSC atau Best Supportive Care
PEMILIHAN OBAT KEMOTERAPI
 Platinum based ( Sisplatin atau Karboplatin )
 Umumnya kombinasi 2 obat anti-kanker (Etoposid,
Dosetaksel, Gemsitabin, Paklitaksel, Vinorelbin)
 Pilih efek samping (Toksisitas) obat yang minimal
 Respon terapi dinilai dengan kriteria RECIST
Tersedia di Fornas dan e-katalog
PENGOBATAN KANKER PARU
JENIS KARSINOMA SEL KECIL
1. Stage terbatas
• Kemoterapi + radiasi dada
dan profilaxis cranial
irradiation (PCI)
• EP : sisplatin/karboplatin
dengan etoposid
(rotinsulu)
• Reseksi bedah diikuti
dengan kemoterapi atau
kemoterapi plus radiasi jika
tidak ada pembesaran KGB
Pedoman Nasional Penanganan Kanker – Kanker Paru, Kemenkes RI, 2015
2. Stage lanjut
– Kemoterapi kombinasi
– Radiasi paliatif pada lesi primer dan lesi metastasis
• Rekuren:
– Terapi radiasi paliatif
– Kemoterapi paliatif
– Uji klinik
Pedoman Nasional Penanganan Kanker – Kanker Paru, Kemenkes RI, 2015
PENGOBATAN KANKER PARU
JENIS KARSINOMA BUKAN SEL KECIL
Stadium I:
•
•
•
•
Reseksi bedah
Radiasi: bila bedah tidak dapat dilakukan
Kemoterapi: bila bedah tidak dapat dilakukan
Kombinasi terapi memberi hasil lebih baik
Pedoman Nasional Penanganan Kanker – Kanker Paru, Kemenkes RI, 2015
Stadium II :
• Reseksi bedah
• Radiasi:
– bila bedah tidak dapat dilakukan atau pascabedah
(adjuvant) dilakukan bila ada sisa tumor atau
keterlibatan KGB intratoraks
• Kemoterapi:
– bila bedah tidak dapat dilakukan atau pascabedah
(adjuvant) jika ada keterlibatan KGB intratoraks
• Kombinasi terapi memberi hasil lebih baik
Pedoman Nasional Penanganan Kanker – Kanker Paru, Kemenkes RI, 2015
Stadium III-A:
• Kemoterapi neoadjuvat
• Reseksi bedah (bila tumor masih operabel)
• Radiasi pada pasien yang tidak dapat
dilakukan bedah atau pascabedah
• Kombinasi terapi memberikan hasil lebih baik.
• Kemoterapi 4 – 6 siklus pada pasien yang tidak
dapat dibedah
Pedoman Nasional Penanganan Kanker – Kanker Paru, Kemenkes RI, 2015
Stadium III-B:
• Pilihan pengobatan tergantung pada klinis dan
tampilan umum pasien
• Radiasi: pada lesi primer, lesi metastasis dan KGB
supraklavikula
• Kemoterapi 4-6 siklus
• Kombinasi dengan radiasi memberikan hasil yang
lebih baik
Pedoman Nasional Penanganan Kanker – Kanker Paru, Kemenkes RI, 2015
Stadium IV:
• Radiasi paliatif
• Kemoterapi paliatif
• Kombinasi terapi tergantung kondisi klinis
Pedoman Nasional Penanganan Kanker – Kanker Paru, Kemenkes RI, 2015
New Response Evaluation Criteria in Solid Tumours: Revised RECIST Guideline, European Journal of Cancer, 2009
Bila progresif / rekuren..
• Kemoterapi lini kedua:
– Monoterapi doksetaksel
– Monoterapi pemetreksat
– Kombinasi dua obat baru (non platinum rejimen)
TERGETED THERAPY
Epidermal Growth Factor Receptor –
Tyrosine Kinase Inhibitor
(EGFR-TKI)
Epidermal Growth Factor Receptor (EGFR)
 EGFR is a receptor located at
the cell membrane
 Activated by binding of specific
ligand (EGF, TGFα)
 EGFR will undergo dimerization
(homo or heterodimer), which
in turns activates Tyrosine
kinase
Epidermal Growth Factor Receptor (EGFR)
Tyrosine Kinase inhibitor
EGFR mutation incidence
OPTIMAL: 1L Erlotinib vs chemotherapy in
EGFR Mut+ NSCLC
 Chemo naїve
Erlotinib
150mg/day
 Stage IIIB/IV NSCLC
 EGFR activating Mut+
R
(exon 19 deletion or exon 21
L858R mutation)
1:1
Gemcitabine (1,000mg/m2 d1,8) +
carboplatin (AUC5 d1)
q3w, up to 4 cycles
 ECOG PS 0–2
(n=165)
Phase III, open-label, active-controlled
Primary endpoint
Secondary endpoints
Stratification factors
 PFS
 OS
 Mutation type
 ORR
 Histology
 TTP
 Smoking status
 DoR
 HR QoL
Zhou C, et al. J Clin Oncol 2012;30 (Suppl. 15 Pt I):485s (Abs. 7520)
OPTIMAL
:
PFS
Result
OPTIMAL: PFS Results
Wang J, et al. Chicago Multidisciplinary Symposium in Thoracic Oncology 2010. Abstract 18.
EURTAC: 1L Tarceva vs chemotherapy in
EGFR Mut+ NSCLC
Erlotinib
150mg/day
 Chemo naїve
 Stage IIIB/IV NSCLC
 EGFR exon 19 deletion or exon
21 L858R mutation
R
1:1
 ECOG PS 0–2
Platinum-based doublet
chemotherapy
q3wks x 4 cycles*
(n=173)
Phase III, open-label, active-controlled
Primary endpoint
Secondary endpoints
Stratification factors
 PFS
 ORR
 Mutation type
 OS
 ECOG PS
 EGFR mutation analysis in serum
*Cisplatin 75mg/m2 d1 / docetaxel
75mg/m2 d1; cisplatin 75mg/m2 d1 /
gemcitabine 1,250mg/m2 d1,8;
carboplatin AUC6 d1 / docetaxel
75mg/m2 d1; carboplatin
AUC5 d1 / gemcitabine 1,000mg/m2 d1,8
Rosell R, et al. Lancet Oncol 2012;13:239–46
EURTAC
:
PFS
Result
OPTIMAL: PFS Results
Wang J, et al. Chicago Multidisciplinary Symposium
in Thoracic
Oncology
Abstract 18.
Rosell R,
et al. Lancet
Oncol2010.
2012;13:239–46
TATALAKSANA KOMPLIKASI
Cancer pain
Type of Cancer Pain
• Chronic Pain
• Pain lasting for more
than 3 months.
• More subjective and not
as easily described as
acute pain.
• Chronic cancer pain
often involves persistent
pain and breakthrough
pain
Toth, US Pharm, 2009; 34(11):3-12
Oral or Transdermal?
Fentanyl has better profile of side effects
compare to Oral Morphine
SR-morphine 15-30 mg/12h (n=641)
Durogesic 25 mcg/h(n=1884)
50
% Pasien
45
*p<0.001
40
*
35
30
25
*
20
15
10
*
*
5
0
dizziness
Nausea
Somnolence
Vomiting
Constipation
Clark AJ, et al. Curr Med Res Opin 2004;20:1419-28
Incidence of Abuse after Medical Use of Opioids
0.8
0.7
0.6
Oxycodon
0.5
0.4
0.3
Meperidine
0.2
Morphine
0.1
Fentanyl patch
0
1990
1991
1992
1993
1994
1995
David E. Joranson, JAMA 2000.
1996
Transdermal Fentanyl:
Low Addictive Potential
DAWN mentions
per adjusted gram
in the population (USA)
200
150
100
Oxycodone
50
Morphine
Fentanyl
0
1997
1998
1999
2000
2001
Based on mentions as recorded in the Drug Abuse Warning Network database (Substance Abuse
& Mental Health Service Administration), divided by grams per 100.000 populations (adjusted for
equivalency)
Nowak S, et all. Pain Medicine 2004; 2: 59-65
Fentanyl patch May Be The 1st Choice:
•
•
•
•
•
•
•
Difficulty or pain when swallowing
Persistent nausea and/or vomiting
Gastrointestinal obstruction
Poor compliance with oral medications
Tablet/morphine phobia
Unacceptable morphine side effects
Renal failure
Palliative Care Formulary (PCF)
The Scottish Intercollegiate Guidelines Network (SIGN) Guidelines No 44
John Welsh, Palliative Medicine 2005; 19: 9/16
Fentanyl Transderm Patch: Easy to Use
When is Fentanyl Transderm
Patch Appropriate?
• Indicated for the management of chronic
pain that
– cannot be managed by lesser means such as
acetaminophen-opioid
combinations, nonsteroidal analgesics, or prn
dosing with short-acting opioids
– requires continuous opioid administration
• No ceiling dose for effective analgesia
(Durogesic® PI, 2000)
Optimal Dose Fentanyl for Cancer Pain
62 yr man, Rectal cancer
Home care hospice unit during last 3.5 months
C.C ; severe anal pain(verbal pain scale 10/10)
. 150 ug/hr TTS
. Adjuvant Tx
- amitriptyline 50mg/d
- dexamethasone 4mg/d
. Increased gradually to
1,000 ug/hr
with good pain control
(verbal pain scale 1-4 /10)
<Menahem S, et al. J Am Board Fam Pract 2004;17:388-390>
Summary
• Tatalaksana berdasarkan:
–
–
–
–
Histologi
Stadium
Performance status
Komplikasi
• Pengobatan:
–
–
–
–
Pembedahan
Kemoterapi
Radioterapi
Targeted therapy
Multi modality
• Penilaian terapi dengan RECIST
• Targeted therapy (gefitinib, erlotinib) harus
berdasarkan status mutasi EGFR
• Fentanyl transderm patch sangat baik untuk
chronic cancer pain (moderate – severe pain)
dg efek samping minimal
• Semua modalitas pengobatan telah tersedia di
BPJS dan Fornas