kemot terapi
DESCRIPTION
kemoterapiTRANSCRIPT
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KEMOTERAPI
Dra. Endang Martiniani M.Pharm., Apt
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KANKERa/ akibat perubahan regulasi dari proliferasi, diferensiasi dan migrasi yg mrp suatu proses genetika & ada sel yg memp kemampuan proliferasi
FAKTOR PENYEBAB KANKER1. GENETIKA
Ada hub yg kuat antara bbrp peny turunan dg kanker Mis. : Familial polyposis coli colorectal adenocarcinoma Fanconi anemialeukemia akut Down's syndrome leukemia akut Mutasi gen RB1retinoblastomaosteosarcoma
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2. KIMIA Rokok CA paru, larynx, bladder, mulut Asbes CA paru Aflatoxin CA hepar Aniline dyes CA ginjal, ureter, bladder
3. VIRAL HPV = human pabilloma virus Epstein - Barr virus Hepatitis B
4. FISIK = radiasi, trauma / inflamasi kronik
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STADIUM DALAM KANKERSbg suatu ukuran tk keparahan penyakitIndikator prognostikSalah satu cara u/ mengetahui terapi CA rasionalU/ mambandingkan hasil terapi
STADIUM / STAGING0 : sel-sel CA dpt dihilangkan dg cara operasi / dg
prosedur non invrasineI : invasi pd drh lokal, blm ada metastaseII : penyebaran msh bersifat lokal & minimal III : sel-sel CA sdh menyebar & penyebarannya adh
ekstensif / meluasIV : metastase meluas
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SIKLUS SEL CAM
G2 G1 G0
S
mitosis
Sintesa prot& RNA
Sintesa &prod enzim
Faseistirahat
Sel-selmati
Diferensiasi(maturasi mjd sel2
yg tdk membelah)
Sintesa DNA
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KEMOTERAPI
cell-cycle phase non spesific eg : cyclophospamid, doxorubicin
cell-cycle phase spesific eg : MTX, FU
KEMOTERAPI : suatu terapi kanker dg menggunakan obat2 anti kanker (cytotoxic) u/ meng- hancurkan sel-sel CA
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Cellcycle sel2 CA lebih lama dp sel2 normalSel2 normal : 24 - 48 jamSel2 CA : 72 - 120 jam
doneSpesifik
% su
rviv
ing
doneNon-spesifik
100%
% s
urvi
ving
KEMOTERAPI : suatu terapi kanker dg menggunakanobat2 anti kanker cytotoxic u/ menghancur-kan sel-sel CA
100%
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KECAPATAN PERTUMBUHAN SEL2 CA
log
[Jum
lah
sel]
Pertumb sel2 normal
Pertumb sel2 CA
diving resting
Massa sel2 CA Massa sel2 normal
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PENDEKATAN TERAPI1. Pencegahan2. Deteksi awal
mis. : - perubahan kebiasaan BAB - luka yg tidak sembuh2
- perdarahan yg tdk normal - sulit menelan / mencerna - pap smear, mammography, PASARI
3. Terapi4. Terapi paliatif
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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 hrinfus kontinu
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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
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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
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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 )
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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
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INTENSIFICATIONTerapi diberikan sth terapi awal yg tdk terlalu intensifStd terapi u/ penderita :
yg memp. respon bagus pd terapi awalkemungkinan besar memp long term remissionkemungkinan u/ sembuh
Penderita pd klasifikasi tsb diberikan terapi yg lbh intensif Transplantasi sumsum tulang diberikan kmd
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CONSOLIDATIONSth 1x complate remission didapatkanDiberikan u/ kemungkinan cure rate
MAINTENANCEu/ pend dg resiko relapse tinggi pd saat remisiLong term & dosis rendah
SALVAGE THERAPYu/ tujuan penyembuhan sth terapi awal gagal
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NEO ADJUVANT / PRIMARYSbg bag dr terapi kuratifKemoterapi diberikan sebelum operasi / radiasiUntuk mengecilkan sel CA shg mudah diambilDiterapkan bila
CA cenderung bersifat lokalCA diketahui responsif thd sitostatika pd stadium lanjut
Cara Pemberian Kemo :Intra vena - IntrathecalTablet / kapsul - IntracavityIntra muscular - CreamSubcutan
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KLASIFIKASI SITOSTATIKAAlkylating agents
nitrogen 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
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Anti-metabolitesfolic acid analog : methrotrexatepyrimidine analog : fluorouracilcytidine analog: cytarabine, gemcitabinepurine analog : mercaptopurine, fludarabinehydroxyurea
Vinca alkaloids : vincristine, vinblastineEpidophyllotoxins : etoposide, teniposide
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Carboplatin : ovarian Ca, cervix Ca, endometrium Ca, Ca of head & neck, breast Ca, lung CaCisplatin : idem, brain tumors, NHL Carmustine : Hodgkin’s & non-Hodgkin’s, MM, lymphoma, colorectal, stomach & liver Ca, brain tumorsCyclophosphamide : Hodgkin’s & non-Hodgkin’s, neuroblastoma, Ca ovary, breast Ca, MMBleomycin : endometrium Ca, Ca ovary, Ca kidney/bladder, Kaposi’s sarcoma, soft tissue sarcomaDaunorubicin : ANLL, ALL, CML, NHL, Kaposi’s sarcoma, neuroblastoma
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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
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Asparaginase :almost all types of leukemiaEtoposide : ALL, ANLL, breast Ca, prostate Ca, Hodgkin’s & non-Hodgkin’s, neuroblastoma, lung Ca, bladder Ca, Kaposi’s sarcomaVinblastine : Hodgkin’s & non-Hodgkin’s, Ca of testis, breast Ca, Kaposi’s sarcoma, choriocarcinomaVincristine : ANLL, ALL, Hodgkin’s & non-Hodgkin’s, rhabdomyosarcoma, MM, Ca cervix, head & neck Ca, kidney
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Cytarabine : almost all types of leukemiaFluorouracil : Ca colon, rectum pancreas, breast Ca, Ca cervix, endometrium, ovary, Ca prostate, bladder, lung, liverHydroxyurea : CML, melanoma, Ca head & neck, Ca ovary, cervix, prostate, MMMercaptopurine : ANLL, ALL, CML, NHLMTX : choriocarcinoma, Ca cervix, ovary, prostate, testis, kidney, breast Ca, ALL, ANLL, NHL, MM, Ca esophagus, stomach
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EFEK SAMPING SITOSTATIKA1. Supresi Sumsum Tulang Belakang (BM)
a. Infeksi bakteri, fungi atau viusNeutropeniaSebab lain : perubahan sistem imun k/ sel2 tumorperubahan permukaan kulit / mukosamalnutrisiKuman 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
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2. Nausea & Vomiting dpt dose limiting tox3. Diare, konstipasi4. Mouth ulcer mucous membrane ulceration5. Allopecia6. Cachexia
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ANEMIAPenyebab 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 kemoterapiTerapi : transfusi SDM, recombinant Epo
terapi supportive
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NEUTROPENIAANC < 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)
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Gejala Klinis InfeksiSuhu > 38oCMengginggil
InflamasiGatal RR
General malaiseBengkak
Sakit kepalaTdk dpt menganggukUrinary +/- rasa sakit
Batuk +/- sputumtendernes
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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
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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
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PRINSIP MANAGEMENT FEBRILE NEUTROPENIA
Broad spectrum AB bila : ANC < 500/mm3, suhu >38.5oC, 3x kenaikan suhu menuju > 38oCKultur & 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
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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
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Gejala :BruisingPetechiaePurpuraHypermenorrheaHematemesisMelenaEpistaxisHematuria
Terapi : transfusi platelet
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GASTROINTESTINAL TOXICITYNausea, 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
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terapiTgt emetogenic potential dr kemoterapiMod – highly serotonin antagonist iv / PPI iv + dexamethasone ivMod serotonin antagonist po, PPILow risk prochloperazine, serotonin antagonist, PPICorticosteroid efektif bila kombinasi dg anti-emetik yg lainDelayed emesis highly emetogenic chemo
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STOMATITISHigienitas oralBisa muncul sekitar 7 hari sth kemotx diberikanBleomycin, daunorubicin, doxorubicin, 5-FU, busulfan, etoposide, , 6-mercaptopurine, vinblastine, vincristineFaktor resiko : dosis, siklus, kombinasi kemotx, fungsi liver & heparProfilaksis : kumur chlorhexidine, saline, NabicTerapi : salep myconazole
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DIARE
Penyebab : anxiety, diet, terapi, infeksi, radiasi, tumor, obstruksi, kemotx.Cytarabine, 5-FU, hydroxyurea, MTX, Pencegahan :hindari mkn yg mengiritasi & menstimulasimkn & mnm kaya K (kentang, pisang, asparagus)Hindari produk susuTerapi : karbon aktif
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KONSTIPASIMkn 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
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CACHEXIA
Hilangnya nafsu mkn berat badanPenyebab :perubh di GIT fatigueES terapi perubh hormonalinfeksi faktor psikologiantibiotik, analgesik rasa sakitkomplikasi dr penyakitTerapi : Megace
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RENAL TOXICITYCyclophosphamide, ifosfamide toksisitas pd bladder (hemorraghic toxicity)antidote : mesnapencegahan : hydration solution w/ NSMTX toksisitas pd tubuluspencegahan : hydration, cukup urinasi antidote : leucovorinMitomycin Nitrosureas : toksisitas pd tubulus & glomerular
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PULMONARY TOXICITY
Sering tjd bleomycin, carmustine, mitomycinJarang tjd cyclophosphamide, doxorubicin, MTX, vinblastine, vincristineTerapi : corticosteroid & simptomatik