PMID- 21803569 OWN - NLM STAT- MEDLINE DCOM- 20120309 LR - 20220316 IS - 1879-0852 (Electronic) IS - 0959-8049 (Linking) VI - 48 IP - 3 DP - 2012 Feb TI - An international expanded-access programme of everolimus: addressing safety and efficacy in patients with metastatic renal cell carcinoma who progress after initial vascular endothelial growth factor receptor-tyrosine kinase inhibitor therapy. PG - 324-32 LID - 10.1016/j.ejca.2011.06.054 [doi] AB - BACKGROUND AND OBJECTIVES: The RECORD-1 trial established the clinical benefit of everolimus in patients with metastatic renal cell carcinoma (mRCC) after failure of initial vascular endothelial growth factor receptor-tyrosine kinase inhibitor (VEGFr-TKI) therapy. The REACT (RAD001 Expanded Access Clinical Trial in RCC) study was initiated to address an unmet medical need by providing everolimus prior to commercial availability, and also to further assess the safety and efficacy of everolimus in patients with VEGFr-TKI-refractory mRCC. PATIENTS AND METHODS: REACT (Clinicaltrials.gov: NCT00655252) was a global, open-label, expanded-access programme in patients with mRCC who were intolerant of, or who had progressed on or after stopping treatment with, any available VEGFr-TKI therapy. Patients received everolimus 10mg once daily, with dose and schedule modifications allowed for toxicity. Patients were closely monitored for the development of serious and grades 3/4 adverse events (AEs). Response was assessed by RECIST every 3months for the first year and every 6months thereafter. RESULTS: A total of 1367 patients were enroled. Safety findings and tumour responses were consistent with those observed in RECORD-1, with no new safety issues identified. The most commonly reported serious AEs were dyspnoea (5.0%), pneumonia (4.7%) and anaemia (4.1%), and the most commonly reported grades 3/4 AEs were anaemia (13.4%), fatigue (6.7%) and dyspnoea (6.5%). Best overall response was stable disease in 51.6% and partial response in 1.7% of patients. Median everolimus treatment duration was 14weeks. CONCLUSION: Everolimus is well tolerated in patients with mRCC and demonstrates a favourable risk-benefit ratio. CI - Copyright (c) 2011 Elsevier Ltd. All rights reserved. FAU - Grunwald, Viktor AU - Grunwald V AD - Clinic for Hematology, Hemostasis, Oncology, and Stem Cell Transplantation, Medical School Hannover, Hannover, Germany. gruenwald.viktor@mh-hannover.de FAU - Karakiewicz, Pierre I AU - Karakiewicz PI FAU - Bavbek, Sevil E AU - Bavbek SE FAU - Miller, Kurt AU - Miller K FAU - Machiels, Jean-Pascal AU - Machiels JP FAU - Lee, Se-Hoon AU - Lee SH FAU - Larkin, James AU - Larkin J FAU - Bono, Petri AU - Bono P FAU - Rha, Sun Young AU - Rha SY FAU - Castellano, Daniel AU - Castellano D FAU - Blank, Christian U AU - Blank CU FAU - Knox, Jennifer J AU - Knox JJ FAU - Hawkins, Robert AU - Hawkins R FAU - Anak, Oezlem AU - Anak O FAU - Rosamilia, Marianne AU - Rosamilia M FAU - Booth, Jocelyn AU - Booth J FAU - Pirotta, Nicoletta AU - Pirotta N FAU - Bodrogi, Istvan AU - Bodrogi I CN - REACT Study Group LA - eng SI - ClinicalTrials.gov/NCT00655252 PT - Clinical Trial PT - Journal Article PT - Multicenter Study DEP - 20110729 PL - England TA - Eur J Cancer JT - European journal of cancer (Oxford, England : 1990) JID - 9005373 RN - 0 (Antineoplastic Agents) RN - 0 (Immunosuppressive Agents) RN - 0 (Protein Kinase Inhibitors) RN - 9HW64Q8G6G (Everolimus) RN - EC 2.7.10.1 (Receptors, Vascular Endothelial Growth Factor) RN - W36ZG6FT64 (Sirolimus) SB - IM MH - Adult MH - Aged MH - Aged, 80 and over MH - Antineoplastic Agents/*therapeutic use MH - Carcinoma, Renal Cell/*drug therapy/secondary MH - Everolimus MH - Female MH - Humans MH - Immunosuppressive Agents/adverse effects/*therapeutic use MH - Kidney Neoplasms/*drug therapy MH - Male MH - Middle Aged MH - Neoplasm Metastasis MH - Protein Kinase Inhibitors/*therapeutic use MH - Receptors, Vascular Endothelial Growth Factor/*antagonists & inhibitors MH - Sirolimus/adverse effects/*analogs & derivatives/therapeutic use MH - Treatment Failure MH - Young Adult FIR - Romedi, M IR - Romedi M FIR - Ferrandini, S IR - Ferrandini S FIR - Rondinon, M IR - Rondinon M FIR - Pittman, K IR - Pittman K FIR - Goldstein, D IR - Goldstein D FIR - Shapiro, J IR - Shapiro J FIR - Troon, S IR - Troon S FIR - Yip, D IR - Yip D FIR - Mainwaring, P IR - Mainwaring P FIR - Zigeuner, R IR - Zigeuner R FIR - Loidl, W IR - Loidl W FIR - Greil, R F IR - Greil RF FIR - Schmidinger, M IR - Schmidinger M FIR - De Greve, J IR - De Greve J FIR - Rottey, S IR - Rottey S FIR - Vermorken, J IR - Vermorken J FIR - Machiels, J IR - Machiels J FIR - Gil, T IR - Gil T FIR - Gennigens, C IR - Gennigens C FIR - Roumeguere, T IR - Roumeguere T FIR - Barrios, C IR - Barrios C FIR - Mathias, C IR - Mathias C FIR - Assi, H IR - Assi H FIR - Hotte, S IR - Hotte S FIR - Karakiewicz, P IR - Karakiewicz P FIR - Knox, J IR - Knox J FIR - Spadafora, S IR - Spadafora S FIR - Wood, L IR - Wood L FIR - Zalewski, P IR - Zalewski P FIR - Mackensie, M IR - Mackensie M FIR - Bjarnason, G IR - Bjarnason G FIR - Lalancette, A IR - Lalancette A FIR - Chan, A IR - Chan A FIR - Higgins, B IR - Higgins B FIR - North, S IR - North S FIR - Soulieres, D IR - Soulieres D FIR - Asselah, J IR - Asselah J FIR - Sperlich, C IR - Sperlich C FIR - Miller, W IR - Miller W FIR - Yadav, S IR - Yadav S FIR - El-Maraghi, R IR - El-Maraghi R FIR - Godoy, J IR - Godoy J FIR - Prausova, J IR - Prausova J FIR - Katolicka, J IR - Katolicka J FIR - Petruzelka, L IR - Petruzelka L FIR - Kiss, I IR - Kiss I FIR - Bono, P IR - Bono P FIR - Lapela, M IR - Lapela M FIR - Miller, K IR - Miller K FIR - Grunwald, V IR - Grunwald V FIR - Bergmann, L IR - Bergmann L FIR - Beck, J IR - Beck J FIR - Jager, E IR - Jager E FIR - Kindler, M IR - Kindler M FIR - Overkamp, F IR - Overkamp F FIR - Wirth, M IR - Wirth M FIR - Holzer, W IR - Holzer W FIR - Gschwend, J IR - Gschwend J FIR - Stenzl, A IR - Stenzl A FIR - Gauler, T IR - Gauler T FIR - Niederwieser, D IR - Niederwieser D FIR - Marschner, N IR - Marschner N FIR - Luck, A IR - Luck A FIR - Tessen, H IR - Tessen H FIR - Eichelberg, C IR - Eichelberg C FIR - Steiner, T IR - Steiner T FIR - Goebell, P IR - Goebell P FIR - Kettner, E IR - Kettner E FIR - Bakhshandeh-Bath, A IR - Bakhshandeh-Bath A FIR - Wilhelm, M IR - Wilhelm M FIR - Schmitz, S IR - Schmitz S FIR - Jacob, A IR - Jacob A FIR - Bierer, S IR - Bierer S FIR - Kube, U IR - Kube U FIR - Staehler, M IR - Staehler M FIR - Engel, E IR - Engel E FIR - Frambach, M IR - Frambach M FIR - Schellenberger, U IR - Schellenberger U FIR - Albers, P IR - Albers P FIR - Simon, J IR - Simon J FIR - Gleissler, M IR - Gleissler M FIR - Klotz, T IR - Klotz T FIR - Repp, R IR - Repp R FIR - Kroning, H IR - Kroning H FIR - Westermann, J IR - Westermann J FIR - Rebmann, U IR - Rebmann U FIR - Brehmer, B IR - Brehmer B FIR - Niederle, N IR - Niederle N FIR - Grund, C IR - Grund C FIR - Verpoort, K IR - Verpoort K FIR - Fonara, P IR - Fonara P FIR - Rassweiler, J IR - Rassweiler J FIR - Bamias, A IR - Bamias A FIR - Fountzilas, G IR - Fountzilas G FIR - Razis, E IR - Razis E FIR - Mouratidou, D IR - Mouratidou D FIR - Georgoulias, V IR - Georgoulias V FIR - Samantas, E IR - Samantas E FIR - Bodrogi, I IR - Bodrogi I FIR - Mangel, L IR - Mangel L FIR - Szanto, J IR - Szanto J FIR - Berger, R IR - Berger R FIR - Pe'er, A IR - Pe'er A FIR - Sella, A IR - Sella A FIR - Ben-Yosef, R IR - Ben-Yosef R FIR - Nechushtan, H IR - Nechushtan H FIR - Crino, L IR - Crino L FIR - Bracarda, S IR - Bracarda S FIR - Ciuffreda, L IR - Ciuffreda L FIR - Graiff, C IR - Graiff C FIR - Falcone, A IR - Falcone A FIR - Roselli, M IR - Roselli M FIR - Sternberg, C IR - Sternberg C FIR - Santoro, A IR - Santoro A FIR - Ruggeri, E IR - Ruggeri E FIR - Bearz, A IR - Bearz A FIR - Venturini, M IR - Venturini M FIR - Aglietta, M IR - Aglietta M FIR - Amadori, D IR - Amadori D FIR - Di Costanzo, F IR - Di Costanzo F FIR - Bari, M IR - Bari M FIR - Gebbia, N IR - Gebbia N FIR - Conte, P IR - Conte P FIR - Bonetti, A IR - Bonetti A FIR - Bordonaro, R IR - Bordonaro R FIR - Cascinu, S IR - Cascinu S FIR - Contu, A IR - Contu A FIR - Cruciani, G IR - Cruciani G FIR - Gasparro, D IR - Gasparro D FIR - Nardi, M IR - Nardi M FIR - Lelli, G IR - Lelli G FIR - Lo Re, G IR - Lo Re G FIR - Boccardo, F IR - Boccardo F FIR - Lorusso, V IR - Lorusso V FIR - Maiello, E IR - Maiello E FIR - Manente, P IR - Manente P FIR - Passalacqua, R IR - Passalacqua R FIR - Piantedosi, F IR - Piantedosi F FIR - Porta, C IR - Porta C FIR - Sacco, C IR - Sacco C FIR - Tondini, C IR - Tondini C FIR - De Placido, S IR - De Placido S FIR - Carteni, G IR - Carteni G FIR - Dogliotto, L IR - Dogliotto L FIR - Rosti, G IR - Rosti G FIR - Milella, M IR - Milella M FIR - Roila, F IR - Roila F FIR - Amoroso, D IR - Amoroso D FIR - Farina, G IR - Farina G FIR - Al-Khatib, H IR - Al-Khatib H FIR - Lee, S IR - Lee S FIR - Kim, T IR - Kim T FIR - Ahn, J IR - Ahn J FIR - Lim, H IR - Lim H FIR - Rha, S IR - Rha S FIR - Chung, I IR - Chung I FIR - Kim, J IR - Kim J FIR - Chung, J IR - Chung J FIR - Ghosn, M IR - Ghosn M FIR - Shameseddine, A IR - Shameseddine A FIR - Lugo, R IR - Lugo R FIR - Cabrera, P IR - Cabrera P FIR - Osanto, S IR - Osanto S FIR - Groenewegen, G IR - Groenewegen G FIR - Blank, C IR - Blank C FIR - van den Eertwegh, F IR - van den Eertwegh F FIR - van Herpen, C IR - van Herpen C FIR - Oosting, S IR - Oosting S FIR - Soetekouw, P IR - Soetekouw P FIR - Lilleby, W IR - Lilleby W FIR - Klepp, O IR - Klepp O FIR - Guren, T IR - Guren T FIR - Alcedo, J IR - Alcedo J FIR - Karlov, P IR - Karlov P FIR - Nosov, D IR - Nosov D FIR - Roman, L IR - Roman L FIR - Rusakov, I IR - Rusakov I FIR - Bazarbashi, S IR - Bazarbashi S FIR - Toh, C IR - Toh C FIR - Mardiak, J IR - Mardiak J FIR - del Muro Solans, F Garcia IR - del Muro Solans F FIR - Ray, J Maroto IR - Ray J FIR - Mollins, J Bellmunt IR - Mollins JB FIR - Castellano, D IR - Castellano D FIR - Martinez, I Duran IR - Martinez I FIR - Gonzalez, B Mellado IR - Gonzalez B FIR - Santasusana, M Domenech IR - Santasusana M FIR - Piqueras, M Lopez-Brea IR - Piqueras M FIR - Fuentes, J Campillo IR - Fuentes JC FIR - Larriba, J Gonzalez IR - Larriba J FIR - Caro, R Luque IR - Caro R FIR - Garcia, A Meana IR - Garcia AM FIR - Aparicio, L IR - Aparicio L FIR - Lopez, N Batista IR - Lopez N FIR - Aragon, V Calderero IR - Aragon V FIR - Morales, C Valverde IR - Morales C FIR - Figueiras, M IR - Figueiras M FIR - Ibanez, J Contreras IR - Ibanez J FIR - Billalabeitia, Gonzalez IR - Billalabeitia G FIR - Estrada, E IR - Estrada E FIR - Arranz, J IR - Arranz J FIR - Sorrosal, J Lambea IR - Sorrosal J FIR - Lozano, A IR - Lozano A FIR - de Villena, M Codes IR - de Villena M FIR - Espinosa, E IR - Espinosa E FIR - Lopez, R IR - Lopez R FIR - Perez, J IR - Perez J FIR - Laurell, A IR - Laurell A FIR - Stierner, U IR - Stierner U FIR - Cwikiel, M IR - Cwikiel M FIR - Borner, M IR - Borner M FIR - Dietrich, P -Y IR - Dietrich P- FIR - Rothermundt, C IR - Rothermundt C FIR - Pu, Y IR - Pu Y FIR - Chang, Y IR - Chang Y FIR - Ou, Y IR - Ou Y FIR - Chuang, C IR - Chuang C FIR - Liao, Y IR - Liao Y FIR - Srimuninnimit, V IR - Srimuninnimit V FIR - Sriuranpong, V IR - Sriuranpong V FIR - Bavbek, S IR - Bavbek S FIR - Buyukberber, S IR - Buyukberber S FIR - Yalcin, B IR - Yalcin B FIR - Goker, E IR - Goker E FIR - Yalcin, S IR - Yalcin S FIR - Geldart, T IR - Geldart T FIR - Wagstaff, J IR - Wagstaff J FIR - Nicholson, S IR - Nicholson S FIR - Chowdhury, S IR - Chowdhury S FIR - Bahl, A IR - Bahl A FIR - Jones, R IR - Jones R FIR - Azzabi, A IR - Azzabi A FIR - Chao, D IR - Chao D FIR - Fife, K IR - Fife K FIR - Hawkins, R IR - Hawkins R FIR - Larkin, J IR - Larkin J FIR - Mead, G IR - Mead G FIR - Nathan, P IR - Nathan P FIR - Pandha, H IR - Pandha H FIR - Hajdenberg, J IR - Hajdenberg J FIR - Gabrail, N IR - Gabrail N FIR - Nimeh, N IR - Nimeh N FIR - Logan, T IR - Logan T FIR - Flaig, T IR - Flaig T FIR - Schraeder, R IR - Schraeder R FIR - Rini, B IR - Rini B FIR - O'Rourke, M IR - O'Rourke M FIR - Alemany, C IR - Alemany C FIR - Beck, J IR - Beck J FIR - Kessinger, A IR - Kessinger A FIR - Amin, A IR - Amin A FIR - Arriaga, M IR - Arriaga M FIR - Rodriguez, J IR - Rodriguez J EDAT- 2011/08/02 06:00 MHDA- 2012/03/10 06:00 CRDT- 2011/08/02 06:00 PHST- 2011/04/12 00:00 [received] PHST- 2011/06/16 00:00 [revised] PHST- 2011/06/24 00:00 [accepted] PHST- 2011/08/02 06:00 [entrez] PHST- 2011/08/02 06:00 [pubmed] PHST- 2012/03/10 06:00 [medline] AID - S0959-8049(11)00492-8 [pii] AID - 10.1016/j.ejca.2011.06.054 [doi] PST - ppublish SO - Eur J Cancer. 2012 Feb;48(3):324-32. doi: 10.1016/j.ejca.2011.06.054. Epub 2011 Jul 29.