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JOURNAL READING
Increased Survival with Enzalutamide in Prostate Cancer after Chemotherapy
Presented by :Afifah Nur Kartikasari
012.095.821
Adviser : Prof. Dr. dr. H Rifki Muslim Sp. B, Sp. U
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Identitas Jurnal
Title• Increased Survival with
Enzalutamide in Prostate Cancer after Chemotherapy
Author• Howard I. Scher, M.D., Karim
Fizazi, M.D., Ph.D., Fred Saad, M.D.,
Publisher •New England Journal of Medicine
Date •September 27 2012
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Backgroud
Kanker prostat (androgen dependent) yang awalnya merespon menjadi resisten terhadap terapi yang menurunkan sirkulasi testosteron atau menghambat ikatan androgen pada reseptor androgen
Enzalutamide (sebelumnya disebut MDV3100) bekerja pada jalur sinyal reseptor androgen,yang merupakan pendorong utama pertumbuhan kanker prostat.
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Method
3 phase
Double blind
Placebo-controlled trial
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Histological or cytologically confirmed diagnosis of prostate cancer
Castrate level of testosterone <50ng/deciliter
Previous treatment with docetaxel
Progressive disease (PCWG2)
Increasing PSA
Radiography confirmed progression with or without a rise in PSA level
INCLUSION CRITERIA
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1199 men with castration resistant prostate cancer after chemotherapy
Receive oral Enzalutamide (800) 160mg/daily or Placebo (399)
Primary End Point was overall survival
Phase 1-2 trial enrolling men with castration resistant prostate cancer
Phase 3 trial, evaluate whether enzalutamide would prolong life in men with progresisive prostate cancer after chemotherapy
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Secondary End Point
proportion of patients with a reduction in the prostate-specific antigen (PSA) level by 50% or more
the soft-tissue response rate
the quality-of-life response rate
the time to PSA progression
radiographic progression-free survival
the time to the first skeletal-related event
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308 of 800 patients (39%) died in the enzalutamide group and 212 of 399 patients (53%) died in the placebo group.
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Secondary End pointEnzalutamide Placebo p
PSA-level response rate 54% 2% <0,001
soft-tissue response rate 29% 4% <0,001
quality-of-life response 43% 18% <0,001
the time to PSA progression 8,3 month 3,0 month <0,001
radiographic progression-free survival
8,3 month 2,9 month <0,001
the time to the first skeletal-related event
16,7 month 13,3 month <0,001
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In this phase 3 study, we found that enzalutamide, an oral androgen-receptor–signaling inhibitor, significantly prolonged the survival of men with metastatic castration-resistant prostate cancer after chemotherapy by a median of 4.8 months and reduced the risk of death from any cause by 37% versus placebo.
DISCUSSION
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Enzalutamide Inhibits Multiple Steps in the AR Signaling Pathway
Mukherji D et al. Expert Opin Investig Drugs 2012;21:227-33. Carson C et al. Urology 2003;61:2-7.
Testosterone/DHT Enzalutamide
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Conclusion
Enzalutamide significantly prolonged the survival of men with metastatic
castrationresistant prostate cancer after chemotherapy.
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CRITICAL APPRAISAL• Judul :
Increased Survival with Enzalutamide in Prostate Cancer after Chemotherapy
– Sudah sesuai dengan isi penelitian
– Penulisan judul < 12 kata
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Terdiri dari 4 paragraf
Komponen : terdiri dari introduction, methods,results, dan conclusions
Kurang dari 250 kata
ABSTRACT
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PICO ANALYSISPatients
• 1199 men with castration-resistant prostate cancer after chemotherapy according to the eastern Cooperative Oncology Group Performance-status score and pain intensity
Intervention • Enzalutamide
Comparison • Placebo
Outcome
• Reduction in the prostate-spesific antigen(PSA) level by 50% or more.
• the soft tissue response rate• The quality of life response rate , the time to PSA
progression, time to first skeletal-related event
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Apakah terkumpul sebuah sampel pasien yang jelas dan representatif pada titik awal perjalanan penyakit?
Ya
Apakah pengamatan pasien cukup panjang dan lengkap?
Ya
Apakah kriteria kesudahan yang obyektif diterapkan secara blind?
Ya
•Apakah dilakukan penyesuaian utk faktor prognosis yang penting?•Apakah dilakukan validasi pada kelompok pasien tes set yang independent?
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CRITICAL APPRAISAL
Apakah bukti tentang aspek prognosis ini valid?
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Apakah bukti tentang aspek prognosis yang valid ini penting?
Seberapa besar kemungkinan kesudahan ini terjadi untuk jangka waktu yang lebih panjang?
Ya
Survival time Enzalutamide 18,4 month
Seberapa presisi estimasi prognosis? Ya
CI 95%, 0,53-0,75
P< 0,001
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Apakah kita dapat menerapkan bukti tentang aspek prognosis yang valid dan penting ini pada pasien kita?
Apakah pasien dalam penelitian ini mirip/serupa dengan pasien kita?
Ya
Apakah bukti ini mempunyai pengaruh yang penting secara klinis terhadap kesimpulan kita tentang apa yang perlu ditawarkan atau diberitahukan kepada pasien kita
Ya
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VALID
DAPAT DITERAPKAN
PENTING
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THANK YOU...