Tesis

Efektivitas dan Keamanan Sorafenib Dosis Inisiasi 400 mg Dibandingkan Sorafenib Dosis Inisiasi 800 mg terhadap Kesintasan Pasien Karsinoma Sel Hati Stadium Lanjut dan Intermediet: Suatu Telaah Sistematis dan Meta-analisis = Effectiveness and Safety of Sorafenib 400 mg Initial Dose Compared with Sorafenib 800 mg Initial Dose on Survival in Patients with Advanced and Intermediate Stage Hepatocellular Carcinoma: A Systematic Review and Meta-analysis.

Latar Belakang: sorafenib adalah suatu multi-tyrosine kinase inhibitor yang terbukti dapat memperbaiki kesintasan pasien karsinoma sel hati (KSH) stadium lanjut dan stadium intermediet yang tidak respons dengan terapi lokoregional. Berdasarkan pencarian hingga saat ini penelitian-penelitian yang mengevaluasi efektivitas dan keamanan dosis inisiasi sorafenib 400 mg dibandingkan sorafenib dosis inisiasi 800 mg terhadap kesintasan pasien KSH stadium lanjut dan intermediet sudah cukup banyak, namun hasil penelitian terdahulu menunjukkan hasil yang bervariasi. Tujuan: mengetahui efektivitas sorafenib dosis inisiasi 400 mg dibandingkan dosis 800 mg terhadap kesintasan pasien KSH stadium lanjut dan intermediet serta efek samping yang ditimbulkannya pada kedua kelompok. Metode: kami melakukan penelusuran sistematis dari Randomized Controlled Trials dan Non-randomized Studies of Interventinons di PUBMED, EMBASE, EBSCO, PROQUEST, snowballing, Global Index Medicus, GARUDA, SINTA, dan perpustakaan digital beberapa universitas di Indonesia hingga 30 April 2021. Dari 603 artikel, terdapat 5 studi NRSI yang memenuhi kriteria eligibilitas. Data dianalisis menggunakan Review Manager 5.4.1. Hasil: sorafenib dosis inisiasi 400 mg memiliki efektivitas yang lebih baik terhadap overall survival dibandingkan pemberian sorafenib dosis 800 mg pada pasien KSH stadium lanjut dan intermediet secara bermakna (HR 0,84; IK 95% 0,71–0,98; p=0,03). Tidak didapatkan perbedaan kejadian efek samping secara keseluruhan pada berbagai derajat di kedua kelompok (pooled OR 0,93; IK 95% 0,67–1,30; p=0,68). Simpulan: sorafenib dosis inisiasi 400 mg memiliki efektivitas yang lebih baik terhadap overall survival dengan kejadian efek samping yang tidak berbeda bermakna dibandingkan sorafenib dosis 800 mg pada pasien KSH stadium lanjut dan intermediet.
Kata Kunci: karsinoma sel hati, sorafenib, overall survival, efek samping


Background: sorafenib is a multi-tyrosine kinase inhibitor that has been shown to improve survival in patients with advanced and intermediate stage hepatocellular carcinoma (HCC). Based on the search to date, there are quite number of studies evaluating the effectiveness and safety of sorafenib 400 mg compared to sorafenib 800 mg on the survival of patients with advanced and intermediate HCC; however, the previous studies have showed varying results. Objective: to determine the effectiveness of sorafenib 400 mg initial dose compared with sorafenib 800 mg initial dose on survival in patients with advanced and intermediate HCC and its side effects in both groups. Method: we performed a systematic search of Randomized Controlled Trials and NonRandomized Studies of Interventions from PUBMED, EMBASE, EBSCO, PROQUEST, snowballing, global index medicus, GARUDA, SINTA and several digital libraries of universities in Indonesia until April 30, 2021. Of the 603 articles, there were 5 NRSI studies that met the eligibility criteria. Data were analyzed using Review Manager 5.4.1. Results: sorafenib 400 mg initial dose was significantly more effective on overall survival compared to sorafenib 800 mg initial dose in patients with advanced and intermediate HCC (HR 0.84; 95% CI 0.71–0.98; p=0.03). There was no difference in the overall incidence of adverse events to various degrees between the two groups (pooled OR 0.93; 95% CI 0.67–1.30; p=0.68). Conclusion: sorafenib 400 mg initial dose has a better effectiveness on overall survival with not significantly difference in the incidence of adverse events compared to sorafenib 800 mg initial dose in patients with advanced and intermediate HCC.
Keywords: hepatocellular carcinoma, sorafenib, overall survival, side effects