핵의학

본문글자크기
  • [Lancet Oncol.] Efficacy and safety of selective internal radiotherapy with yttrium-90 resin microspheres compared with sorafenib in locally advanced and inoperable hepatocellular carcinoma (SARAH): an open-label randomised controlled phase 3 trial.

    Assistance Publique-Hôpitaux de Paris / ValérieVilgrain*

  • 출처
    Lancet Oncol.
  • 등재일
    2017 Dec
  • 저널이슈번호
    18(12):1624-1636.
  • 내용

    바로가기  >

    Abstract

    BACKGROUND:
    Sorafenib is the recommended treatment for patients with advanced hepatocellular carcinoma. We aimed to compare the efficacy and safety of sorafenib to that of selective internal radiotherapy (SIRT) with yttrium-90 (90Y) resin microspheres in patients with hepatocellular carcinoma.

    METHODS:
    SARAH was a multicentre, open-label, randomised, controlled, investigator-initiated, phase 3 trial done at 25 centres specialising in liver diseases in France. Patients were eligible if they were aged at least 18 years with a life expectancy greater than 3 months, had an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1, Child-Pugh liver function class A or B score of 7 or lower, and locally advanced hepatocellular carcinoma (Barcelona Clinic Liver Cancer [BCLC] stage C), or new hepatocellular carcinoma not eligible for surgical resection, liver transplantation, or thermal ablation after a previously cured hepatocellular carcinoma (cured by surgery or thermoablative therapy), or hepatocellular carcinoma with two unsuccessful rounds of transarterial chemoembolisation. Patients were randomly assigned (1:1) by a permutated block method with block sizes two and four to receive continuous oral sorafenib (400 mg twice daily) or SIRT with 90Y-loaded resin microspheres 2-5 weeks after randomisation. Patients were stratified according to randomising centre, ECOG performance status, previous transarterial chemoembolisation, and presence of macroscopic vascular invasion. The primary endpoint was overall survival. Analyses were done on the intention-to-treat population; safety was assessed in all patients who received at least one dose of sorafenib or underwent at least one of the SIRT work-up exams. This study has been completed and the final results are reported here. The trial is registered with ClinicalTrials.gov, number NCT01482442.

    FINDINGS:
    Between Dec 5, 2011, and March 12, 2015, 467 patients were randomly assigned; after eight patients withdrew consent, 237 were assigned to SIRT and 222 to sorafenib. In the SIRT group, 53 (22%) of 237 patients did not receive SIRT; 26 (49%) of these 53 patients were treated with sorafenib. Median follow-up was 27·9 months (IQR 21·9-33·6) in the SIRT group and 28·1 months (20·0-35·3) in the sorafenib group. Median overall survival was 8·0 months (95% CI 6·7-9·9) in the SIRT group versus 9·9 months (8·7-11·4) in the sorafenibgroup (hazard ratio 1·15 [95% CI 0·94-1·41] for SIRT vs sorafenib; p=0·18). In the safety population, at least one serious adverse event was reported in 174 (77%) of 226 patients in the SIRT group and in 176 (82%) of 216 in the sorafenib group. The most frequent grade 3 or worse treatment-related adverse events were fatigue (20 [9%] vs 41 [19%]), liver dysfunction (25 [11%] vs 27 [13%]), increased laboratory liver values (20 [9%] vs 16 [7%]), haematological abnormalities (23 [10%] vs 30 [14%]), diarrhoea (three [1%] vs 30 [14%]), abdominal pain (six [3%] vs 14 [6%]), increased creatinine (four [2%] vs 12 [6%]), and hand-foot skin reaction (one [<1%] vs 12 [6%]). 19 deaths in the SIRT group and 12 in the sorafenib group were deemed to be treatment related.

    INTERPRETATION:
    In patients with locally advanced or intermediate-stage hepatocellular carcinoma after unsuccessful transarterial chemoembolisation, overall survival did not significantly differ between the two groups. Quality of life and tolerance might help when choosing between the two treatments.

    FUNDING:
    Sirtex Medical Inc.

     

     

    Author information

    Vilgrain V1, Pereira H2, Assenat E3, Guiu B3, Ilonca AD4, Pageaux GP3, Sibert A5, Bouattour M5, Lebtahi R5, Allaham W5, Barraud H6, Laurent V6, Mathias E6, Bronowicki JP6, Tasu JP7, Perdrisot R7, Silvain C7, Gerolami R8, Mundler O9, Seitz JF8, Vidal V9, Aubé C10, Oberti F10, Couturier O10, Brenot-Rossi I11, Raoul JL11, Sarran A11, Costentin C12, Itti E12, Luciani A13, Adam R14, Lewin M14, Samuel D14, Ronot M15, Dinut A2, Castera L15, Chatellier G16; SARAHTrial Group.
    1
    Assistance Publique-Hôpitaux de Paris, Hôpitaux Universitaires Paris Nord Val de Seine, Hôpital Beaujon, Clichy, France; Université Paris Diderot, Sorbonne Paris Cité, Faculté de Médecine, Paris, France; INSERM U1149, Centre de Recherche de l'Inflammation (CRI), Paris, France. Electronic address: valerie.vilgrain@aphp.fr.
    2
    Assistance Publique-Hôpitaux de Paris, Hôpital Européen Georges-Pompidou, Unité de Recherche Clinique, Paris, France; INSERM, Centre d'Investigation Clinique 1418 (CIC1418), Paris, France.
    3
    Centre Hospitalier Universitaire de Montpellier, Hôpital Saint Eloi, Montpellier, France.
    4
    Centre Hospitalier Universitaire de Montpellier, Hôpital Gui de Chauliac, Montpellier, France.
    5
    Assistance Publique-Hôpitaux de Paris, Hôpitaux Universitaires Paris Nord Val de Seine, Hôpital Beaujon, Clichy, France.
    6
    Centre Hospitalier Universitaire de Nancy, Hôpital de Brabois, Vandoeuvre-lès-Nancy, France.
    7
    Centre Hospitalier Universitaire de Poitiers, Poitiers, France.
    8
    Assistance Publique-Hôpitaux de Marseille, Hôpital de la Timone, Marseille, France; Université Aix-Marseille, Marseille, France.
    9
    Assistance Publique-Hôpitaux de Marseille, Hôpital de la Timone, Marseille, France.
    10
    Centre Hospitalier Universitaire d'Angers, Angers, France.
    11
    Institut Paoli Calmettes, Marseille, France.
    12
    Assistance Publique-Hôpitaux de Paris, Hôpital Henri Mondor, Créteil, France.
    13
    Assistance Publique-Hôpitaux de Paris, Hôpital Henri Mondor, Créteil, France; Université Paris Est Créteil, Faculté de Médecine, Créteil, France; INSERM IMRB U955 Equipe 18, Créteil, France.
    14
    Assistance Publique-Hôpitaux de Paris, Hôpital Paul Brousse, Villejuif, France.
    15
    Assistance Publique-Hôpitaux de Paris, Hôpitaux Universitaires Paris Nord Val de Seine, Hôpital Beaujon, Clichy, France; Université Paris Diderot, Sorbonne Paris Cité, Faculté de Médecine, Paris, France; INSERM U1149, Centre de Recherche de l'Inflammation (CRI), Paris, France.
    16
    Assistance Publique-Hôpitaux de Paris, Hôpital Européen Georges-Pompidou, Unité de Recherche Clinique, Paris, France; INSERM, Centre d'Investigation Clinique 1418 (CIC1418), Paris, France; Université Paris-Descartes, Sorbonne Paris Cité, Faculté de Médecine, Paris, France.

     

    Collaborators (103)

    Assenat E, Delhom-Christol E, Guiu B, Ilonca AD, Lonjon J, Pageaux GP, Abdel-Rehim M, Allaham W, Bouattour M, Castera L, Dieudonné A, Lebtahi R, Ronot M, Sibert A, Vilgrain V, Barraud H, Bazin C, Bronowicki JP, Laurent V, Mathias E, Chagneau-Derrode C, Perdrisot R, Silvain C, Tasu JP, Borentain P, Gerolami R, Mundler O, Seitz JF, Vidal V, Aubé C, Bouvier A, Couturier O, Oberti F, Vervueren L, Brenot-Rossi I, Raoul JL, Sarran A, Chalaye J, Costentin C, Itti E, Kobeiter H, Luciani A, Adam R, Lewin M, Samuel D, Edeline J, Garin E, Rolland Y, Archambeaud I, Eugene T, Frampas E, Cassinotto C, Guyot M, Hiriart JB, Lapuyade B, Vergniol J, Bachellier P, Detour J, Duclos B, Greget M, Habersetzer F, Imperiale A, Merle P, Rode A, Morvan J, Nguyen-Khac E, Yzet T, Baudin G, Chevallier P, Mahamat A, Piche T, Razzouk M, Hillon P, Loffroy R, Toubeau M, Vincent J, Barabino G, Bouarioua N, Cuilleron M, Ecochard M, Prevot-Bitot N, Leroy V, Roux J, Sengel C, Bourcier V, Ganne-Carrie N, Seror O, Costo S, Dao T, Pelage JP, Dumortier J, Giammarile F, Valette PJ, Ghazzar N, Pellerin O, Taieb J, Weinmann P, Heurgue-Berlot A, Marcus C, Sommacale D, Castilla-Lièvre MA, Maitre S, Marthey L.

  • 덧글달기
    덧글달기
       IP : 44.200.175.255

    등록