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