https://scholars.lib.ntu.edu.tw/handle/123456789/431422
標題: | First-line selective internal radiotherapy plus chemotherapy versus chemotherapy alone in patients with liver metastases from colorectal cancer (FOXFIRE, SIRFLOX, and FOXFIRE-Global): a combined analysis of three multicentre, randomised, phase 3 trials | 作者: | Wasan, Harpreet S. GRACE PEN-HSIU CHAO Sharma, Navesh K. Taieb, Julien Heinemann, Volker Ricke, Jens Peeters, Marc Findlay, Michael Weaver, Andrew Mills, Jamie Wilson, Charles ADRIAN RAUCHFLEISCH Francis, Anne Moschandreas, Joanna Virdee, Pradeep S. Dutton, Peter Love, Sharon Gebski, Val Gray, Alastair Bateman, Andrew Blesing, Claire BEI-EN CHANG Chau, Ian Cummins, Sebastian Cunningham, David Falk, Stephen Hadaki, Maher Hall, Marcia Hickish, Tamas Hornbuckle, Joanne Lofts, Fiona Lowndes, Sarah Mayer, Astrid Metcalfe, Matthew Middleton, Gary Montazeri, Amir Muirhead, Rebecca Polychronis, Andreas Purcell, Colin RICHARD PING CHENG Sharma, Ricky A. Sherwin, Liz Smith, David Soomal, Rubin Swinson, Daniel Walther, Axel Wilson, Greg Amin, Pradip AN-BANG WANG Balosso, Jacques Beny, Alex Bloomgarden D. BEI-EN CHANG Bruch, Harald Robert Bui, James Burge, Matthew Cardaci, Giuseppe Carlisle, James Chai, Seungjean Chen, Yi Jen Chevallier, Patrick Chuong, Michael Clarke, Stephen Coveler, Andrew Craninx, Michael Delanoit, Thierry Deleporte A. Eliadis, Paul Facchini, Francis Ferguson, Thomas Ferrante, Michel Frenette, Gary Frick, Jacob Ganju, Vinod Garofalo, Michael KAI-PING GRACE YAO Gehbauer, Gerald George, Benjamin Geva, Ravit Gordon, Michael KAI-PING GRACE YAO Gulec, Seza Hannigan, James van Hazel, Guy Heching, Norman Helmberger, Thomas Hendlisz, Alain Hendrickx, Koen Holtzman, Matthew I-RUE LAI Jackson, Christopher James, Philip KATHERINE ANN KIM Karapetis, Chris KATHERINE ANN KIM Ko, Yon Dschun Kr?ning, Hendrik Lammert, Frank Liauw, Winston JIN-TUNG LIANG Louafi S. de Man M. Margolis J. Martin R. Martoni A. Marx G. Matos M. Monsaert E. Moons V. Nott L. Nusch A. O'Donnell A. Ozer H. Padia S. Pavlakis N. Perez D. Pluntke S. Polus M. Powell A. Pracht M. Price T. Ransom D. Rebischung C. Ridwelski K. Riera-Knorrenschild J. Riess H. Rilling W. Robinson B. Rodr?guez J. Sanchez F. Sauerbruch T. Savin M. Scheidhauer K. Schneiderman E. Seeger G. Segelov E. Schmueli E.S. Shani A. Shannon J. Shibata S. Singhal N. Smith D. Smith R. Stemmer S. St?tzer O. Strickland A. Tatsch K. Terrebonne E. Tichler T. Vehling-Kaiser U. Vera-Garcia R. Vogl T. Walpole E. Wang E. Whiting S. Wolf I. Ades S. Aghmesheh M. Auber M. Ayala H. Boland P. Bouche E. Bowers C. Bremer C. Casado A.R. Cooray P. Crain M. De Wit M. Dowling K. Durand A. Faivre S. Feeney K. Ferru A. Fragoso M. Granetto C. Hammel P. Issacs R. Iyer R. Kim Y.H. Lim L. Liu J.H. Masi G. Mosconi S. Numico G. Ratner L. Sae-Won H. Singh M. Stoltzfus P. Tan I. Trogu A. Underhill C. Westcott M. FOXFIRE trial investigators, SIRFLOX trial investigators, FOXFIRE-Global trial investigators, SIRFLOX trial investigators, FOXFIRE-Global trial investigators, FOXFIRE-Global trial investigators |
公開日期: | 1-九月-2017 | 卷: | 18 | 期: | 9 | 來源出版物: | The Lancet Oncology | 摘要: | © 2017 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 license Background Data suggest selective internal radiotherapy (SIRT) in third-line or subsequent therapy for metastatic colorectal cancer has clinical benefit in patients with colorectal liver metastases with liver-dominant disease after chemotherapy. The FOXFIRE, SIRFLOX, and FOXFIRE-Global randomised studies evaluated the efficacy of combining first-line chemotherapy with SIRT using yttrium-90 resin microspheres in patients with metastatic colorectal cancer with liver metastases. The studies were designed for combined analysis of overall survival. Methods FOXFIRE, SIRFLOX, and FOXFIRE-Global were randomised, phase 3 trials done in hospitals and specialist liver centres in 14 countries worldwide (Australia, Belgium, France, Germany, Israel, Italy, New Zealand, Portugal, South Korea, Singapore, Spain, Taiwan, the UK, and the USA). Chemotherapy-naive patients with metastatic colorectal cancer (WHO performance status 0 or 1) with liver metastases not suitable for curative resection or ablation were randomly assigned (1:1) to either oxaliplatin-based chemotherapy (FOLFOX: leucovorin, fluorouracil, and oxaliplatin) or FOLFOX plus single treatment SIRT concurrent with cycle 1 or 2 of chemotherapy. In FOXFIRE, FOLFOX chemotherapy was OxMdG (oxaliplatin modified de Gramont chemotherapy; 85 mg/m 2 oxaliplatin infusion over 2 h, L-leucovorin 175 mg or D,L-leucovorin 350 mg infusion over 2 h, and 400 mg/m 2 bolus fluorouracil followed by a 2400 mg/m 2 continuous fluorouracil infusion over 46 h). In SIRFLOX and FOXFIRE-Global, FOLFOX chemotherapy was modified FOLFOX6 (85 mg/m 2 oxaliplatin infusion over 2 h, 200 mg leucovorin, and 400 mg/m 2 bolus fluorouracil followed by a 2400 mg/m 2 continuous fluorouracil infusion over 46 h). Randomisation was done by central minimisation with four factors: presence of extrahepatic metastases, tumour involvement of the liver, planned use of a biological agent, and investigational centre. Participants and investigators were not masked to treatment. The primary endpoint was overall survival, analysed in the intention-to-treat population, using a two-stage meta-analysis of pooled individual patient data. All three trials have completed 2 years of follow-up. FOXFIRE is registered with the ISRCTN registry, number ISRCTN83867919. SIRFLOX and FOXFIRE-Global are registered with ClinicalTrials.gov, numbers NCT00724503 (SIRFLOX) and NCT01721954 (FOXFIRE-Global). Findings Between Oct 11, 2006, and Dec 23, 2014, 549 patients were randomly assigned to FOLFOX alone and 554 patients were assigned FOLFOX plus SIRT. Median follow-up was 43·3 months (IQR 31·6–58·4). There were 411 (75%) deaths in 549 patients in the FOLFOX alone group and 433 (78%) deaths in 554 patients in the FOLFOX plus SIRT group. There was no difference in overall survival (hazard ratio [HR] 1·04, 95% CI 0·90–1·19; p=0·61). The median survival time in the FOLFOX plus SIRT group was 22·6 months (95% CI 21·0–24·5) compared with 23·3 months (21·8–24·7) in the FOLFOX alone group. In the safety population containing patients who received at least one dose of study treatment, as treated, the most common grade 3–4 adverse event was neutropenia (137 [24%] of 571 patients receiving FOLFOX alone vs 186 (37%) of 507 patients receiving FOLFOX plus SIRT). Serious adverse events of any grade occurred in 244 (43%) of 571 patients receiving FOLFOX alone and 274 (54%) of 507 patients receiving FOLFOX plus SIRT. 10 patients in the FOLFOX plus SIRT group and 11 patients in the FOLFOX alone group died due to an adverse event; eight treatment-related deaths occurred in the FOLFOX plus SIRT group and three treatment-related deaths occurred in the FOLFOX alone group. Interpretation Addition of SIRT to first-line FOLFOX chemotherapy for patients with liver-only and liver-dominant metastatic colorectal cancer did not improve overall survival compared with that for FOLFOX alone. Therefore, early use of SIRT in combination with chemotherapy in unselected patients with metastatic colorectal cancer cannot be recommended. To further define the role of SIRT in metastatic colorectal cancer, careful patient selection and studies investigating the role of SIRT as consolidation therapy after chemotherapy are needed. Funding Bobby Moore Fund of Cancer Research UK, Sirtex Medical. |
URI: | https://scholars.lib.ntu.edu.tw/handle/123456789/431422 | ISSN: | 14702045 | DOI: | 10.1016/S1470-2045(17)30457-6 |
顯示於: | 醫學系 |
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