International phase III trial assessing neoadjuvant cisplatin, methotrexate, and vinblastine chemotherapy for muscle-invasive bladder cancer: long-term results of the BA06 30894 trial
International Collaboration of Trialists, Medical Research Council Advanced Bladder Cancer Working Party (now the National Cancer Research Institute Bladder Cancer Clinical Studies Group), European Organisation for Research and Treatment of Cancer Genito-Urinary Tract Cancer Group, Australian Bladder Cancer Study Group, National Cancer Institute of Canada Clinical Trials Group, Finnbladder, Norwegian Bladder Cancer Study Group, Club Urologico Espanol de Tratamiento Oncologico Group, Gareth Griffiths, Reginald Hall, Richard Sylvester, Derek Raghavan, Mahesh K B Parmar, F R Macbeth, W Steward, J M Russell, A N Harnett, R P Symonds, P A Canney, N S Reed, R Jones, M Crawford, J D Graham, H F V Newman, G N A Sibley, A D Chetiyawardana, G Read, D J Cole, A L Harris, P I Clark, J Littler, S Myint, B Cottier, R D Errington, J E S Brock, J Gildersleve, M Snee, A Benghiat, D Guthrie, F Glaholm, D Spooner, D G Arkell, R R Hall, D E Neal, J T Roberts, A Ferro, R Wiltshire, S Coltart, F Madden, R Heal, D Chetiyawardana, S J Harland, G Duchesne, P J Hoskin, E J Maher, J T Roberts, J M Bozzino, A N Branson, H H Lucraft, M Quilty-Windsor, K K Sethia, C G C Gaches, M R H Ashken, C Beacock, D M A Wallace, A D Chetiyawardana, J Glaholm, D Spooner, A G Goodman, N D James, A V Kaisary, A Horwich, C Beacock, A Hay, G M Mead, J Glaholm, P R C Dunlop, A J Rathmell, A Robinson, P Selby, M A Cornbleet, P McDougall, D Nicol, E Walpole, T Sandeman, K H Tai, M Tong, C Lewis, M Friedlander, I Olver, Q Walker, D Raghavan, V Ganju, R McLennan, G M Jeffery, D Perez, S G Allan, C Coppin, N Murray, P Venner, B Findlay, H S Dhaliwal, J H Chritchley, G Armitage, M Gospodarowicz, M Moore, M A S Jewett, I Tannock, W A Wells, S Ernst, D A Stewart, R Choo, Z Wajsman, P Flodgren, R P Abratt, J Rzepecki, G Madej, S D Fossa, N Aass, H Wahre, O Alfthan, R O Fourcade, Bittard, Botto, G Vallencien, B Callet, L Boccon-Gibod, M Marechal, C Theodore, L Denis, P J Van Cangh, K E J Lantsoght, P Carpentier, J Casselman, A Verbaeys, H Van Poppel, C J Van Groeningen, H J Keizer, C H N Veenhof, C Van de Beek, W Kirkels, T A W Splinter, A P M Van der Meijden, P P M Karthaus, G A Dijkman, F Debruyne, H Jansen, C G G Boeken Kruger, A V Bono, A Tizzani, C Sternberg, V Pansadoro, M Pavone-Macaluso, N Flores, R Bastus, J A Martinez-Pineiro, B Martin, J Portillo, L A Rioja, S Isorna, A Santos Garcia Vaquero, M Tallada, J Hetherington, P Whelan, G Studler, J Pont, Z Kirkali, A Akdas, A Borkowski, F Recker, J Kliment, C L Cutajar, R R Hall, G M Mead, J T Roberts, R R Hall, G M Mead, J T Roberts, D M A Wallace, T A W Splinter, F Calais da Silva, C N Sternberg, G Vallencien, D Raghavan, M Gospodarowicz, S Fossa, O Alfhan, J A Martinez-Pineiro, J Heaton, J Schaafsma, A Berner, J Philips, H Richmond, S Nordling, G O Griffiths, M K B Parmar, R J Sylvester, B M Uscinska, M de Pauw, C de Balincourt, M Gospodarowicz, R R Hall, G M Mead, M K B Parmar, D Raghavan, J T Roberts, T A W Splinter, R J Sylvester, A Barrett, H Scher, O Dalesio, International Collaboration of Trialists, Medical Research Council Advanced Bladder Cancer Working Party (now the National Cancer Research Institute Bladder Cancer Clinical Studies Group), European Organisation for Research and Treatment of Cancer Genito-Urinary Tract Cancer Group, Australian Bladder Cancer Study Group, National Cancer Institute of Canada Clinical Trials Group, Finnbladder, Norwegian Bladder Cancer Study Group, Club Urologico Espanol de Tratamiento Oncologico Group, Gareth Griffiths, Reginald Hall, Richard Sylvester, Derek Raghavan, Mahesh K B Parmar, F R Macbeth, W Steward, J M Russell, A N Harnett, R P Symonds, P A Canney, N S Reed, R Jones, M Crawford, J D Graham, H F V Newman, G N A Sibley, A D Chetiyawardana, G Read, D J Cole, A L Harris, P I Clark, J Littler, S Myint, B Cottier, R D Errington, J E S Brock, J Gildersleve, M Snee, A Benghiat, D Guthrie, F Glaholm, D Spooner, D G Arkell, R R Hall, D E Neal, J T Roberts, A Ferro, R Wiltshire, S Coltart, F Madden, R Heal, D Chetiyawardana, S J Harland, G Duchesne, P J Hoskin, E J Maher, J T Roberts, J M Bozzino, A N Branson, H H Lucraft, M Quilty-Windsor, K K Sethia, C G C Gaches, M R H Ashken, C Beacock, D M A Wallace, A D Chetiyawardana, J Glaholm, D Spooner, A G Goodman, N D James, A V Kaisary, A Horwich, C Beacock, A Hay, G M Mead, J Glaholm, P R C Dunlop, A J Rathmell, A Robinson, P Selby, M A Cornbleet, P McDougall, D Nicol, E Walpole, T Sandeman, K H Tai, M Tong, C Lewis, M Friedlander, I Olver, Q Walker, D Raghavan, V Ganju, R McLennan, G M Jeffery, D Perez, S G Allan, C Coppin, N Murray, P Venner, B Findlay, H S Dhaliwal, J H Chritchley, G Armitage, M Gospodarowicz, M Moore, M A S Jewett, I Tannock, W A Wells, S Ernst, D A Stewart, R Choo, Z Wajsman, P Flodgren, R P Abratt, J Rzepecki, G Madej, S D Fossa, N Aass, H Wahre, O Alfthan, R O Fourcade, Bittard, Botto, G Vallencien, B Callet, L Boccon-Gibod, M Marechal, C Theodore, L Denis, P J Van Cangh, K E J Lantsoght, P Carpentier, J Casselman, A Verbaeys, H Van Poppel, C J Van Groeningen, H J Keizer, C H N Veenhof, C Van de Beek, W Kirkels, T A W Splinter, A P M Van der Meijden, P P M Karthaus, G A Dijkman, F Debruyne, H Jansen, C G G Boeken Kruger, A V Bono, A Tizzani, C Sternberg, V Pansadoro, M Pavone-Macaluso, N Flores, R Bastus, J A Martinez-Pineiro, B Martin, J Portillo, L A Rioja, S Isorna, A Santos Garcia Vaquero, M Tallada, J Hetherington, P Whelan, G Studler, J Pont, Z Kirkali, A Akdas, A Borkowski, F Recker, J Kliment, C L Cutajar, R R Hall, G M Mead, J T Roberts, R R Hall, G M Mead, J T Roberts, D M A Wallace, T A W Splinter, F Calais da Silva, C N Sternberg, G Vallencien, D Raghavan, M Gospodarowicz, S Fossa, O Alfhan, J A Martinez-Pineiro, J Heaton, J Schaafsma, A Berner, J Philips, H Richmond, S Nordling, G O Griffiths, M K B Parmar, R J Sylvester, B M Uscinska, M de Pauw, C de Balincourt, M Gospodarowicz, R R Hall, G M Mead, M K B Parmar, D Raghavan, J T Roberts, T A W Splinter, R J Sylvester, A Barrett, H Scher, O Dalesio
Abstract
Purpose: This article presents the long-term results of the international multicenter randomized trial that investigated the use of neoadjuvant cisplatin, methotrexate, and vinblastine (CMV) chemotherapy in patients with muscle-invasive urothelial cancer of the bladder treated by cystectomy and/or radiotherapy. Nine hundred seventy-six patients were recruited between 1989 and 1995, and median follow-up is now 8.0 years.
Patients and methods: This was a randomized phase III trial of either no neoadjuvant chemotherapy or three cycles of CMV.
Results: The previously reported possible survival advantage of CMV is now statistically significant at the 5% level. Results show a statistically significant 16% reduction in the risk of death (hazard ratio, 0.84; 95% CI, 0.72 to 0.99; P = .037, corresponding to an increase in 10-year survival from 30% to 36%) after CMV.
Conclusion: We conclude that CMV chemotherapy improves outcome as first-line adjunctive treatment for invasive bladder cancer. Two large randomized trials (by the Medical Research Council/European Organisation for Research and Treatment of Cancer and Southwest Oncology Group) have confirmed a statistically significant and clinically relevant survival benefit, and neoadjuvant chemotherapy followed by definitive local therapy should be viewed as state of the art, as compared with cystectomy or radiotherapy alone, for deeply invasive bladder cancer.
Conflict of interest statement
Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.
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Source: PubMed