Download - Anti Kanker Yustin
ANTI KANKER
By : Youstiana Dwi Rusita, M.Si.,Apt.
KANKER
a/ akibat perubahan regulasi dari proliferasi, diferensiasi dan migrasi yg mrp suatu proses genetika & ada sel yg mempunyai kemampuan proliferasi
FAKTOR PENYEBAB KANKER1. GENETIKA
Ada hub yg kuat antara bbrp peny turunan dg kanker, Mis. : Familial polyposis coli colorectal adenocarcinoma
Fanconi anemia leukemia akut Down's syndrome leukemia
akut Mutasi gen RB1 retinoblastoma
osteosarcoma
2. KIMIARokok CA paru, larynx, bladder, mulutAsbes CA paruAflatoxin CA heparAniline dyes CA ginjal, ureter, bladder
3. VIRALHPV = human pabilloma virus Epstein - Barr virus Hepatitis B
4. FISIK = radiasi, trauma / inflamasi kronik
STADIUM DALAM KANKERSbg suatu ukuran tk keparahan penyakitIndikator prognostikSalah satu cara u/ mengetahui terapi CA
rasionalU/ mambandingkan hasil terapi
STADIUM / STAGING
0 : sel-sel CA dpt dihilangkan dg cara operasi / dg prosedur non invrasine
I : invasi pd drh lokal, blm ada metastaseII : penyebaran msh bersifat lokal & minimal III : sel-sel CA sdh menyebar &
penyebarannya adh ekstensif / meluas
IV : metastase meluas
SIKLUS SEL CA
M
G2 G1 G0
S
mitosis
Sintesa prot& RNA
Sintesa &prod enzim
Faseistirahat
Sel-selmati
Diferensiasi(maturasi mjd sel2yg tdk membelah)
Sintesa DNA
KEMOTERAPI
cell-cycle phase non spesificeg : cyclophospamid, doxorubicin
cell-cycle phase spesificeg : MTX, FU
KEMOTERAPI : suatu terapi kanker dg menggunakan obat2 anti kanker (cytotoxic) u/ menghancurkan sel-sel CA
Cellcycle sel2 CA lebih lama dp sel2 normalSel2 normal : 24 - 48 jam
Sel2 CA : 72 - 120 jam
done
Spesifik
% s
urv
ivin
g
done
Non-spesifik
100%
% s
urv
ivin
g
KEMOTERAPI : suatu terapi kanker dg menggunakan obat2 anti kanker cytotoxic u/ menghancurkan sel-sel CA
100%
KECEPATAN PERTUMBUHAN SEL2 CAlo
g [J
um
lah s
el]
Pertumb sel2 normal
Pertumb sel2 CA
diving resting
Massa sel2 CA Massa sel2 normal
PENDEKATAN TERAPI1. Pencegahan2. Deteksi awal
mis. : - perubahan kebiasaan BAB - luka yg tidak sembuh2
- perdarahan yg tdk normal - sulit menelan / mencerna - pap smear, mammography,
PASARI3. Terapi4. Terapi paliatif
TERAPIOperasiRadio terapiKemo terapi : sitostatika, hormon, ImmunotherapyKombinasi
Pemberian sitostatika :Diberikan pd bbrp siklusDiberikan kombinasi ( 2, 3 macam obat )Dpt sbg inj bolus tiap 3-4 minggu / 3-5 hr
infus kontinue
Pemberian sitostatika bdskan Jenis kankerKerja kemoterapi relatif thd selKinetika proliferasi sel tumor dibanding jaringan
normalDerajat metastaseKemungkinan u/ adanya mutasi (reisten)Usia Derajat kesehatanGangguan organ vital ( hati & ginjal )
Tujuan Pemberian Sitostatika1. Menyembuhkan (cure)2. Survival / control3. Paliatif
Cure : Bila sel2 tumor dibawah level of detection Relapse tdk tjd dlm 5-10 th sth terapi Mis. : - CA Testicular
- Hodgkinsdisease - Choriocarcinoma
Survival / control :- bila cure tdk memungkinkan- agar sel - sel CA berhenti berkembang- quality of life ( QOL ) dg sisa - sisa sel CA- surgery / radiotherapi dilanjutkan
kemoterapi- respon awal tjd ttp sering timbul relapse- mis. : CA mammal
Small cell lung CA Non Hodgkin's Pymphoma
Paliatif :- CA sdh terminal kemo u/ memperbaiki gejala CA shg
QOL
- Tdk diharapkan tjdnya remisi
- Sitostatika hanya u/ partial remisi gejala klinis membaik
- Pertimbangan pd intensitas & durasi terapi tetap QOL
ADJUVANT CHEMOTHERAPY• Tujuan cure rate dg membasmi sel2 tumor yg
tersisa sth dilakukan terapi primer (mis.: op, rad) • U/ CA yg sdh menyebar u/ control CA• Mencegah pertumbuhan sel-sel CA sth op / rad
( level of detection )
ADJUVANT CHEMO
Jml sel tumor 0-103
Tujuan : menyembuhkan
s/d 75 % penderita bebas dr sel2 tumor
Short term toxicity : highlong term toxicity : low
CONVENTIONAL
CHEMO Jml sel tumor 0-109
Tujuan : survival/paliatif( kadang2 cure )
Tdk ada pend yg bebas dr sel tumor
Toksisitas dpt diterima
INTENSIFICATION
Terapi diberikan sth terapi awal yg tdk terlalu intensif
Std terapi u/ penderita :◦yg memp. respon bagus pd terapi awal◦kemungkinan besar memp long term
remission◦kemungkinan u/ sembuh
Penderita pd klasifikasi tsb diberikan terapi yg lbh intensif
Transplantasi sumsum tulang diberikan kmd.
CONSOLIDATION◦Sth 1x complate remission didapatkan◦Diberikan u/ kemungkinan cure rate
MAINTENANCE◦u/ pend dg resiko relapse tinggi pd saat
remisi◦Long term & dosis rendah
SALVAGE THERAPY◦u/ tujuan penyembuhan sth terapi awal
gagal
NEO ADJUVANT / PRIMARYSbg bag dr terapi kuratifKemoterapi diberikan sebelum operasi / radiasiUntuk mengecilkan sel CA shg mudah diambilDiterapkan bila
◦CA cenderung bersifat lokal◦CA diketahui responsif thd sitostatika pd stadium
lanjut
Cara Pemberian Kemo :◦Intra vena - Intrathecal◦Tablet / kapsul - Intracavity◦Intra muscular - Cream◦Subcutan
KLASIFIKASI SITOSTATIKA
Alkylating agentsnitrogen mustard : mustine HCl, cyclophosphamide, ifosfamide, chlorambucilnitrosoureas : lomustine, carmustine, streptozineplatinum/metal salts : cisplatin, carboplatinalkyl sulfonate : busulfan
Natural Productsmitotic inhibitor : vinblastin, vincristinmicrotubule polymer stabilizer : paclitaxel, doxitaxelpodophyllum derv : etoposideantibiotic : doxorubicin/Adriamycin, daunorubicin, bleomycin, mitomycinenzyme : asparaginase
Anti-metabolitesfolic acid analog : methrotrexatepyrimidine analog : fluorouracilcytidine analog: cytarabine, gemcitabinepurine analog : mercaptopurine, fludarabinehydroxyurea
Vinca alkaloids : vincristine, vinblastineEpidophyllotoxins : etoposide, teniposide
Carboplatin : ovarian Ca, cervix Ca, endometrium Ca, Ca of head & neck, breast Ca, lung Ca
Cisplatin : idem, brain tumors, NHL Carmustine : Hodgkin’s & non-Hodgkin’s, MM,
lymphoma, colorectal, stomach & liver Ca, brain tumors
Cyclophosphamide : Hodgkin’s & non-Hodgkin’s, neuroblastoma, Ca ovary, breast Ca, MM
Bleomycin : endometrium Ca, Ca ovary, Ca kidney/bladder, Kaposi’s sarcoma, soft tissue sarcoma
Daunorubicin : ANLL, ALL, CML, NHL, Kaposi’s sarcoma, neuroblastoma
Hormon & hormone antagonist androgen : fluoxymesteronecorticosteroid : prednison, dexamethasoneestrogen : diethylstilbestrolprogestin : megestrol acetate, medroxyprogesterone acetateestrogen antagonist : tamoxifen LHRH : leuprolide, goserelin
Miscellaneous agent :substituted urea : hydroxyureamethylhydrazine derv : procarbazinesteroid synthesis inhibitor : aminoglutethimide
Asparaginase :almost all types of leukemia
Etoposide : ALL, ANLL, breast Ca, prostate Ca, Hodgkin’s & non-Hodgkin’s, neuroblastoma, lung Ca, bladder Ca, Kaposi’s sarcoma
Vinblastine : Hodgkin’s & non-Hodgkin’s, Ca of testis, breast Ca, Kaposi’s sarcoma, choriocarcinoma
Vincristine : ANLL, ALL, Hodgkin’s & non-Hodgkin’s, rhabdomyosarcoma, MM, Ca cervix, head & neck Ca, kidney
Cytarabine : almost all types of leukemiaFluorouracil : Ca colon, rectum pancreas,
breast Ca, Ca cervix, endometrium, ovary, Ca prostate, bladder, lung, liver
Hydroxyurea : CML, melanoma, Ca head & neck, Ca ovary, cervix, prostate, MM
Mercaptopurine : ANLL, ALL, CML, NHLMTX : choriocarcinoma, Ca cervix, ovary,
prostate, testis, kidney, breast Ca, ALL, ANLL, NHL, MM, Ca esophagus, stomach
EFEK SAMPING SITOSTATIKA
1. Supresi Sumsum Tulang Belakang (BM)a. Infeksi bakteri, fungi atau vius
Neutropenia Sebab lain : perubahan sistem imun k/ sel2 tumorperubahan permukaan kulit / mukosa malnutrisi
Kuman patogen :- streptococcus pneumoniae - H. influenzae- sthapylococcus epidermidis - E-coli- Pseudomonas aeruginosa - G(-) & G(+)- jamur (candida sp, aspergillus)- virus (herpes simplex, CMV, varicella, zoster, adeno virus)
b. Thrombocytopeniac. Anemia
2. Nausea & Vomiting dpt dose limiting tox3. Diare, konstipasi4. Mouth ulcer mucous membrane ulceration5. Allopecia6. Cachexia
ANEMIA
Penyebab utama : kemoterapiPenyebab lain : malnutrisi, blood loss, inflitrasi
marrow k/ tumor, prod eritropoietinEtiologi dr blood loss hrs diketahui. Blood loss mens bleeding, thrombositopenia, GI
bleedingCisplatin, cytarabine, paclitaxel plg seringFaktor resiko : kondisi klinis , multiple metastase,
geriatri, gangg jantung, malnutrisi, Hb di siklus awal kemoterapi
Terapi : transfusi SDM, recombinant Epterapi supportive
NEUTROPENIA
ANC < 1500 sel/mm3 resiko infeksi ANC = (neutrophil + band)/100 x WBCPrognosa infeksi derajat neutropeniaTimbul opportunistic inf t.u. dr
endogenous orgn.Strategi :
1. Memicu sistem imunR/ granulocyte colony-stimulating factors (G-CSF)
Gejala Klinis InfeksiSuhu > 38oCMengginggil
InflamasiGatal RR
General malaiseBengkak
Sakit kepalaTdk dpt menganggukUrinary +/- rasa sakit
Batuk +/- sputumtendernes
2. Mempertahankan barrier tubuh yg alami
Menghindari injeksi sedpt mungkinMenghindari catheter sedpt mungkin higienitas di drh oral, rektum, uretra, vagina, jari tangan & kakiKumur dg lar antiseptik / chorhexidine Hindari enema, supp, termometer rektumBila konstipasi : laksatif, stool softenersMembersihkan drh injeksi dg antiseptik
3. Mempertahankan integritas mukosa intestin
Mkn dg Low-microbial containedHigh-fiber diet tgt jenis CA dan kondisi
klinis PxHigh in calories, protein, vitaminCukup fluid intakeNutrisi mgn glutamin, fiber, albuminKumur chlorhexidine
4. Mengurangi koloni environmental microorganisms
PRINSIP MANAGEMENT FEBRILE NEUTROPENIA
Broad spectrum AB bila : ANC < 500/mm3, suhu >38.5oC, 3x kenaikan suhu menuju > 38oC
Kultur & sensitivitas dr catheterMonitor thd secondary infectionsFever > 1 minggu teruskan AB + terapi
antifungalAB hentikan bila ANC > 500/mm3 , psn dg
resiko rendahMycostatin cream bila candidiasis di mulutPrecautions u/ mempertahankan higienitas
THROMBOCYTOPENIA
Platelet < 100.000 sel/mm3
K/ chemoterahpy induces myelosuppresion dose-limitingside effectCarboplatin, carmustine, cyclophosphamide, lomustine, mitomycin, doxorubicin, daunorubicin, vincristin, dactinomycinPlt < 50.000 sel/mm3 resiko bleedingPlt < 10.000 sel/mm3 GI bleed, CNS bleed, resp tract hemorrhage
Gejala :BruisingPetechiaePurpuraHypermenorrheaHematemesisMelenaEpistaxisHematuria
Terapi : transfusi platelet
GASTROINTESTINAL TOXICITY
Nausea, vomiting antiemetic therapy3 pola N-V akut, delayed, anticipatoryAkut dlm 24 jam pertama sth kemoterapiDelayed tjd stlh > 24 jam pertama kemoterapi, durasi 1-7 hari, puncak hr ke-3Delayed dpt tjd msk terapi u/ akut efektifAnticipatory tjd sebelum kemoterapi
TERAPI Tgt emetogenic potential dr
kemoterapi Mod – highly serotonin antagonist
iv / PPI iv + dexamethasone iv Mod serotonin antagonist po, PPI Low risk prochloperazine,
serotonin antagonist, PPI Corticosteroid efektif bila
kombinasi dg anti-emetik yg lain Delayed emesis highly
emetogenic chemo
STOMATITIS
Higienitas oral Bisa muncul sekitar 7 hari sth kemotx
diberikan Bleomycin, daunorubicin, doxorubicin, 5-FU,
busulfan, etoposide, , 6-mercaptopurine, vinblastine, vincristine
Faktor resiko : dosis, siklus, kombinasi kemotx, fungsi liver & hepar
Profilaksis : kumur chlorhexidine, saline, Nabic Terapi : salep myconazole
DIARE∞ Penyebab : anxiety, diet, terapi, infeksi,
radiasi, tumor, obstruksi, kemotx.∞ Cytarabine, 5-FU, hydroxyurea, MTX, ∞ Pencegahan :hindari mkn yg mengiritasi
& menstimulasi∞ mkn & mnm kaya K (kentang, pisang,
asparagus)∞ Hindari produk susu∞ Terapi : karbon aktif
KONSTIPASI
Mkn tinggi serat (sayuran, buah, gandum)Minum air putih 8 gelas/h Olah raga ringanMinuman hangat u/ merangsang aktifitas ususStool softener, laksatifm bulk forming agent (Metamucil, laktulosa)Hindari antikolinergik, preparat Fe, diuretik, fenotiazine, antidepresan
CACHEXIA
Hilangnya nafsu mkn berat badanPenyebab :
perubh di GIT fatigue ES terapi perubh hormonal infeksi faktor psikologi antibiotik, analgesik rasa sakit komplikasi dr penyakit
Terapi : Megace
RENAL TOXICITYCyclophosphamide, ifosfamide toksisitas
pd bladder (hemorraghic toxicity)antidote : mesnapencegahan : hydration solution w/ NS
MTX toksisitas pd tubuluspencegahan : hydration, cukup urinasi antidote : leucovorin
Mitomycin Nitrosureas : toksisitas pd tubulus &
glomerular
PULMONARY TOXICITY
Sering tjd bleomycin, carmustine, mitomycin
Jarang tjd cyclophosphamide, doxorubicin, MTX, vinblastine, vincristine
Terapi : corticosteroid & simptomatik