Difference between revisions of "Bladder cancer - null regimens"

From HemOnc.org - A Hematology Oncology Wiki
Jump to navigation Jump to search
m (Text replacement - "6 PubMed" to "6/ PubMed")
m
 
(16 intermediate revisions by 2 users not shown)
Line 3: Line 3:
 
[[#top|Back to Top]]
 
[[#top|Back to Top]]
 
</div>
 
</div>
The purpose of this page is to provide references to "null therapy" such as placebo and observation. While not clinically relevant, these references provide further insight into the historical development of the treatment landscape. See the [[Bladder cancer|main bladder cancer page]] for current regimens.
+
The purpose of this page is to provide references to "null therapy" such as placebo and observation. These references provide further insight into the historical development of the treatment landscape. See the [[Bladder cancer|main bladder cancer page]] for regimens that include active anticancer treatment.
  
 
{{TOC limit|limit=3}}
 
{{TOC limit|limit=3}}
 +
 
=Nonmuscle invasive bladder cancer/Intravesical chemotherapy=
 
=Nonmuscle invasive bladder cancer/Intravesical chemotherapy=
 
==Observation==
 
==Observation==
Line 32: Line 33:
 
===References===
 
===References===
  
#'''THP Monotherapy Study Group Trial:''' Ito A, Shintaku I, Satoh M, Ioritani N, Aizawa M, Tochigi T, Kawamura S, Aoki H, Numata I, Takeda A, Namiki S, Namima T, Ikeda Y, Kambe K, Kyan A, Ueno S, Orikasa K, Katoh S, Adachi H, Tokuyama S, Ishidoya S, Yamaguchi T, Arai Y. Prospective randomized phase II trial of a single early intravesical instillation of pirarubicin (THP) in the prevention of bladder recurrence after nephroureterectomy for upper urinary tract urothelial carcinoma: the THP Monotherapy Study Group Trial. J Clin Oncol. 2013 Apr 10;31(11):1422-7. Epub 2013 Mar 4. [https://doi.org/10.1200/jco.2012.45.2128 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/23460707 PubMed] UMIN000004039
+
#'''THP Monotherapy Study Group Trial:''' Ito A, Shintaku I, Satoh M, Ioritani N, Aizawa M, Tochigi T, Kawamura S, Aoki H, Numata I, Takeda A, Namiki S, Namima T, Ikeda Y, Kambe K, Kyan A, Ueno S, Orikasa K, Katoh S, Adachi H, Tokuyama S, Ishidoya S, Yamaguchi T, Arai Y. Prospective randomized phase II trial of a single early intravesical instillation of pirarubicin (THP) in the prevention of bladder recurrence after nephroureterectomy for upper urinary tract urothelial carcinoma: the THP Monotherapy Study Group Trial. J Clin Oncol. 2013 Apr 10;31(11):1422-7. Epub 2013 Mar 4. [https://doi.org/10.1200/jco.2012.45.2128 link to original article] [https://pubmed.ncbi.nlm.nih.gov/23460707/ PubMed] UMIN000004039
  
 
==Placebo==
 
==Placebo==
Line 56: Line 57:
 
</div></div>
 
</div></div>
 
===References===
 
===References===
#'''SWOG S0337:''' Messing EM, Tangen CM, Lerner SP, Sahasrabudhe DM, Koppie TM, Wood DP Jr, Mack PC, Svatek RS, Evans CP, Hafez KS, Culkin DJ, Brand TC, Karsh LI, Holzbeierlein JM, Wilson SS, Wu G, Plets M, Vogelzang NJ, Thompson IM Jr. Effect of intravesical instillation of gemcitabine vs saline immediately following resection of suspected low-grade non-muscle-invasive bladder cancer on tumor recurrence: SWOG S0337 randomized clinical trial. JAMA. 2018 May 8;319(18):1880-1888. [https://jamanetwork.com/journals/jama/fullarticle/2680547 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc6583489/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/29801011/ PubMed] NCT00445601
+
#'''SWOG S0337:''' Messing EM, Tangen CM, Lerner SP, Sahasrabudhe DM, Koppie TM, Wood DP Jr, Mack PC, Svatek RS, Evans CP, Hafez KS, Culkin DJ, Brand TC, Karsh LI, Holzbeierlein JM, Wilson SS, Wu G, Plets M, Vogelzang NJ, Thompson IM Jr. Effect of intravesical instillation of gemcitabine vs saline immediately following resection of suspected low-grade non-muscle-invasive bladder cancer on tumor recurrence: SWOG S0337 randomized clinical trial. JAMA. 2018 May 8;319(18):1880-1888. [https://jamanetwork.com/journals/jama/fullarticle/2680547 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc6583489/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/29801011/ PubMed] [https://clinicaltrials.gov/study/NCT00445601 NCT00445601]
  
 
=Neoadjuvant chemotherapy=
 
=Neoadjuvant chemotherapy=
Line 72: Line 73:
 
|1984-1989
 
|1984-1989
 
| style="background-color:#1a9851" |Phase 3 (C)
 
| style="background-color:#1a9851" |Phase 3 (C)
|[[#Cisplatin_monotherapy_99|Cisplatin]]
+
|[[#Cisplatin_monotherapy_999|Cisplatin]]
 
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
 
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
 
|-
 
|-
Line 110: Line 111:
  
 
#Martinez-Piñeiro JA, Gonzalez Martin M, Arocena F, Flores N, Roncero CR, Portillo JA, Escudero A, Jimenez Cruz F, Isorna S. Neoadjuvant cisplatin chemotherapy before radical cystectomy in invasive transitional cell carcinoma of the bladder: a prospective randomized phase III study. J Urol. 1995 Mar;153(3 Pt 2):964-73. [https://www.auajournals.org/doi/full/10.1016/S0022-5347%2801)67614-6 link to original article] [https://pubmed.ncbi.nlm.nih.gov/7853584/ PubMed]
 
#Martinez-Piñeiro JA, Gonzalez Martin M, Arocena F, Flores N, Roncero CR, Portillo JA, Escudero A, Jimenez Cruz F, Isorna S. Neoadjuvant cisplatin chemotherapy before radical cystectomy in invasive transitional cell carcinoma of the bladder: a prospective randomized phase III study. J Urol. 1995 Mar;153(3 Pt 2):964-73. [https://www.auajournals.org/doi/full/10.1016/S0022-5347%2801)67614-6 link to original article] [https://pubmed.ncbi.nlm.nih.gov/7853584/ PubMed]
#'''RTOG 89-03:''' Shipley WU, Winter KA, Kaufman DS, Lee WR, Heney NM, Tester WR, Donnelly BJ, Venner PM, Perez CA, Murray KJ, Doggett RS, True LD. Phase III trial of neoadjuvant chemotherapy in patients with invasive bladder cancer treated with selective bladder preservation by combined radiation therapy and chemotherapy: initial results of Radiation Therapy Oncology Group 89-03. J Clin Oncol. 1998 Nov;16(11):3576-83. [https://doi.org/10.1200/jco.1998.16.11.3576 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/9817278 PubMed]
+
#'''RTOG 89-03:''' Shipley WU, Winter KA, Kaufman DS, Lee WR, Heney NM, Tester WR, Donnelly BJ, Venner PM, Perez CA, Murray KJ, Doggett RS, True LD. Phase III trial of neoadjuvant chemotherapy in patients with invasive bladder cancer treated with selective bladder preservation by combined radiation therapy and chemotherapy: initial results of Radiation Therapy Oncology Group 89-03. J Clin Oncol. 1998 Nov;16(11):3576-83. [https://doi.org/10.1200/jco.1998.16.11.3576 link to original article] [https://pubmed.ncbi.nlm.nih.gov/9817278/ PubMed]
##'''Pooled update:''' Efstathiou JA, Bae K, Shipley WU, Kaufman DS, Hagan MP, Heney NM, Sandler HM. Late pelvic toxicity after bladder-sparing therapy in patients with invasive bladder cancer: RTOG 89-03, 95-06, 97-06, 99-06. J Clin Oncol. 2009 Sep 1;27(25):4055-61. [https://doi.org/10.1200/jco.2008.19.5776 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2734419/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/19636019 PubMed]
+
##'''Pooled update:''' Efstathiou JA, Bae K, Shipley WU, Kaufman DS, Hagan MP, Heney NM, Sandler HM. Late pelvic toxicity after bladder-sparing therapy in patients with invasive bladder cancer: RTOG 89-03, 95-06, 97-06, 99-06. J Clin Oncol. 2009 Sep 1;27(25):4055-61. [https://doi.org/10.1200/jco.2008.19.5776 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2734419/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/19636019/ PubMed]
##'''Pooled update:''' Mak RH, Hunt D, Shipley WU, Efstathiou JA, Tester WJ, Hagan MP, Kaufman DS, Heney NM, Zietman AL. Long-Term Outcomes in Patients With Muscle-Invasive Bladder Cancer After Selective Bladder-Preserving Combined-Modality Therapy: A Pooled Analysis of Radiation Therapy Oncology Group Protocols 8802, 8903, 9506, 9706, 9906, and 0233. J Clin Oncol. 2014 Dec 1;32(34):3801-9. Epub 2014 Nov 3. [https://doi.org/10.1200/jco.2014.57.5548 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4239302/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/25366678 PubMed]
+
##'''Pooled update:''' Mak RH, Hunt D, Shipley WU, Efstathiou JA, Tester WJ, Hagan MP, Kaufman DS, Heney NM, Zietman AL. Long-Term Outcomes in Patients With Muscle-Invasive Bladder Cancer After Selective Bladder-Preserving Combined-Modality Therapy: A Pooled Analysis of Radiation Therapy Oncology Group Protocols 8802, 8903, 9506, 9706, 9906, and 0233. J Clin Oncol. 2014 Dec 1;32(34):3801-9. Epub 2014 Nov 3. [https://doi.org/10.1200/jco.2014.57.5548 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4239302/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/25366678/ PubMed]
 
#'''BA06 30894:''' Griffiths G, Hall R, Sylvester R, Raghavan D, Parmar MK; International Collaboration of Trialists. Neoadjuvant cisplatin, methotrexate, and vinblastine chemotherapy for muscle-invasive bladder cancer: a randomised controlled trial. Lancet. 1999 Aug 14;354(9178):533-40. Erratum in: Lancet 1999 Nov 6;354(9190):1650. [https://doi.org/10.1016/S0140-6736(99)02292-8 link to original article] [https://pubmed.ncbi.nlm.nih.gov/10470696/ PubMed] ISRCTN82694463
 
#'''BA06 30894:''' Griffiths G, Hall R, Sylvester R, Raghavan D, Parmar MK; International Collaboration of Trialists. Neoadjuvant cisplatin, methotrexate, and vinblastine chemotherapy for muscle-invasive bladder cancer: a randomised controlled trial. Lancet. 1999 Aug 14;354(9178):533-40. Erratum in: Lancet 1999 Nov 6;354(9190):1650. [https://doi.org/10.1016/S0140-6736(99)02292-8 link to original article] [https://pubmed.ncbi.nlm.nih.gov/10470696/ PubMed] ISRCTN82694463
##'''Update:''' Griffiths G, Hall R, Sylvester R, Raghavan D, Parmar MK; International Collaboration of Trialists; Medical Research Council Advanced Bladder Cancer Working Party (now the National Cancer Research Institute Bladder Cancer Clinical Studies Group); [[Study_Groups#EORTC|EORTC]] 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. International phase III trial assessing neoadjuvant cisplatin, methotrexate, and vinblastine chemotherapy for muscle-invasive bladder cancer: long-term results of the BA06 30894 trial. J Clin Oncol. 2011 Jun 1;29(16):2171-7. Epub 2011 Apr 18. [https://doi.org/10.1200/jco.2010.32.3139 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3107740/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/21502557 PubMed]
+
##'''Update:''' Griffiths G, Hall R, Sylvester R, Raghavan D, Parmar MK; International Collaboration of Trialists; Medical Research Council Advanced Bladder Cancer Working Party (now the National Cancer Research Institute Bladder Cancer Clinical Studies Group); [[Study_Groups#EORTC|EORTC]] 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. International phase III trial assessing neoadjuvant cisplatin, methotrexate, and vinblastine chemotherapy for muscle-invasive bladder cancer: long-term results of the BA06 30894 trial. J Clin Oncol. 2011 Jun 1;29(16):2171-7. Epub 2011 Apr 18. [https://doi.org/10.1200/jco.2010.32.3139 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3107740/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/21502557/ PubMed]
#'''SWOG S8710:''' Grossman HB, Natale RB, Tangen CM, Speights VO, Vogelzang NJ, Trump DL, deVere White RW, Sarosdy MF, Wood DP Jr, Raghavan D, Crawford ED. Neoadjuvant chemotherapy plus cystectomy compared with cystectomy alone for locally advanced bladder cancer. N Engl J Med. 2003 Aug 28;349(9):859-66. [https://doi.org/10.1056/NEJMoa022148 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/12944571/ PubMed]
+
#'''SWOG S8710:''' Grossman HB, Natale RB, Tangen CM, Speights VO, Vogelzang NJ, Trump DL, deVere White RW, Sarosdy MF, Wood DP Jr, Raghavan D, Crawford ED. Neoadjuvant chemotherapy plus cystectomy compared with cystectomy alone for locally advanced bladder cancer. N Engl J Med. 2003 Aug 28;349(9):859-66. [https://doi.org/10.1056/NEJMoa022148 link to original article] [https://pubmed.ncbi.nlm.nih.gov/12944571/ PubMed]
 
#'''JCOG0209:''' Kitamura H, Tsukamoto T, Shibata T, Masumori N, Fujimoto H, Hirao Y, Fujimoto K, Kitamura Y, Tomita Y, Tobisu K, Niwakawa M, Naito S, Eto M, Kakehi Y; Urologic Oncology Study Group of the Japan Clinical Oncology Group. Randomised phase III study of neoadjuvant chemotherapy with methotrexate, doxorubicin, vinblastine and cisplatin followed by radical cystectomy compared with radical cystectomy alone for muscle-invasive bladder cancer: Japan Clinical Oncology Group Study JCOG0209. Ann Oncol. 2014 Jun;25(6):1192-8. [https://doi.org/10.1093/annonc/mdu126 link to original article] [https://pubmed.ncbi.nlm.nih.gov/24669010/ PubMed] UMIN C000000093
 
#'''JCOG0209:''' Kitamura H, Tsukamoto T, Shibata T, Masumori N, Fujimoto H, Hirao Y, Fujimoto K, Kitamura Y, Tomita Y, Tobisu K, Niwakawa M, Naito S, Eto M, Kakehi Y; Urologic Oncology Study Group of the Japan Clinical Oncology Group. Randomised phase III study of neoadjuvant chemotherapy with methotrexate, doxorubicin, vinblastine and cisplatin followed by radical cystectomy compared with radical cystectomy alone for muscle-invasive bladder cancer: Japan Clinical Oncology Group Study JCOG0209. Ann Oncol. 2014 Jun;25(6):1192-8. [https://doi.org/10.1093/annonc/mdu126 link to original article] [https://pubmed.ncbi.nlm.nih.gov/24669010/ PubMed] UMIN C000000093
#'''KEYNOTE-905:''' NCT03924895
+
#'''KEYNOTE-905:''' [https://clinicaltrials.gov/study/NCT03924895 NCT03924895]
  
 
=Adjuvant chemotherapy=
 
=Adjuvant chemotherapy=
Line 133: Line 134:
 
|1997-2006
 
|1997-2006
 
| style="background-color:#1a9851" |Phase 3 (C)
 
| style="background-color:#1a9851" |Phase 3 (C)
|[[#MVAC_99|MVAC]]
+
|[[#MVAC_999|MVAC]]
 
| style="background-color:#ffffbf" |Did not meet primary endpoint of RFS
 
| style="background-color:#ffffbf" |Did not meet primary endpoint of RFS
 
|-
 
|-
Line 151: Line 152:
 
|2002-2008
 
|2002-2008
 
| style="background-color:#1a9851" |Phase 3 (C)
 
| style="background-color:#1a9851" |Phase 3 (C)
|[[#MVAC_99|MVAC]]
+
|[[#MVAC_999|MVAC]]
 
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
 
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
|-
 
|[https://www.ncbi.nlm.nih.gov/pmc/articles/pmc8495594/ Bellmunt et al. 2021 (IMvigor010)]
 
|2015-2018
 
| style="background-color:#1a9851" |Phase 3 (C)
 
|[[#Atezolizumab_monotherapy_99|Atezolizumab]]
 
| style="background-color:#ffffbf" |Did not meet primary endpoint of DFS<br>Median DFS: 16.6 vs 19.4 mo<br>(HR 1.12, 95% CI 0.93-1.35)
 
 
|-
 
|-
 
|}
 
|}
''Patients in SOGUG 99/01 had pT3-4 and/or pN positive disease with adequate renal function (CrCl greater than 50 mL/min/1.73m<sup>2</sup>). This arm underwent cystectomy and no further treatment. The study prematurely closed due to poor recruitment and lacks adequate power to make firm conclusions.''
+
''Patients in SOGUG 99/01 had pT3-4 and/or pN positive disease with adequate renal function (CrCl more than 50 mL/min/1.73m<sup>2</sup>). This arm underwent cystectomy and no further treatment. The study prematurely closed due to poor recruitment and lacks adequate power to make firm conclusions.''
 
<div class="toccolours" style="background-color:#fdcdac">
 
<div class="toccolours" style="background-color:#fdcdac">
 
====Biomarker eligibility criteria====
 
====Biomarker eligibility criteria====
Line 170: Line 165:
  
 
*[[Surgery#Cystectomy|Cystectomy]]
 
*[[Surgery#Cystectomy|Cystectomy]]
*IMvigor010: [[Surgery#Radical_cystectomy|Radical cystectomy]] or [[Surgery#Nephroureterectomy_with_lymph_node_dissection|nephroureterectomy with lymph node dissection]]
 
  
 
====Subsequent treatment====
 
====Subsequent treatment====
  
*EORTC 30994, upon relapse: [[Bladder_cancer#MVAC_2|MVAC]] x 6
+
*EORTC 30994, upon relapse: First-line [[Bladder_cancer#MVAC_2|MVAC]] x 6
 
</div></div>
 
</div></div>
 
===References===
 
===References===
  
#'''Abstract:''' L. G. Paz-Ares, E. Solsona, E. Esteban, A. Saez, J. Gonzalez-Larriba, A. Anton, M. Hevia, F. de la Rosa, V. Guillem, and J. Bellmunt. Randomized phase III trial comparing adjuvant paclitaxel/gemcitabine/cisplatin (PGC) to observation in patients with resected invasive bladder cancer: Results of the Spanish Oncology Genitourinary Group (SOGUG) 99/01 study. ASCO MEETING ABSTRACTS Jun 22, 2010:LBA4518. [http://meetinglibrary.asco.org/content/51401-74 link to abstract] '''contains dosing details in manuscript'''
+
#'''Abstract:''' L. G. Paz-Ares, E. Solsona, E. Esteban, A. Saez, J. Gonzalez-Larriba, A. Anton, M. Hevia, F. de la Rosa, V. Guillem, and J. Bellmunt. Randomized phase III trial comparing adjuvant paclitaxel/gemcitabine/cisplatin (PGC) to observation in patients with resected invasive bladder cancer: Results of the Spanish Oncology Genitourinary Group (SOGUG) 99/01 study. ASCO MEETING ABSTRACTS Jun 22, 2010:LBA4518. [http://meetinglibrary.asco.org/content/51401-74 link to abstract]
#'''SWOG-4B951:''' Stadler WM, Lerner SP, Groshen S, Stein JP, Shi SR, Raghavan D, Esrig D, Steinberg G, Wood D, Klotz L, Hall C, Skinner DG, Cote RJ. Phase III study of molecularly targeted adjuvant therapy in locally advanced urothelial cancer of the bladder based on p53 status. J Clin Oncol. 2011 Sep 1;29(25):3443-9. Epub 2011 Aug 1. [https://doi.org/10.1200/JCO.2010.34.4028 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3164246/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/21810677 PubMed] NCT00005047
+
#'''SWOG-4B951:''' Stadler WM, Lerner SP, Groshen S, Stein JP, Shi SR, Raghavan D, Esrig D, Steinberg G, Wood D, Klotz L, Hall C, Skinner DG, Cote RJ. Phase III study of molecularly targeted adjuvant therapy in locally advanced urothelial cancer of the bladder based on p53 status. J Clin Oncol. 2011 Sep 1;29(25):3443-9. Epub 2011 Aug 1. [https://doi.org/10.1200/JCO.2010.34.4028 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3164246/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/21810677/ PubMed] [https://clinicaltrials.gov/study/NCT00005047 NCT00005047]
#'''ITNRC CU02:''' Cognetti F, Ruggeri EM, Felici A, Gallucci M, Muto G, Pollera CF, Massidda B, Rubagotti A, Giannarelli D, Boccardo F; Italian National Research Council. Adjuvant chemotherapy with cisplatin and gemcitabine versus chemotherapy at relapse in patients with muscle-invasive bladder cancer submitted to radical cystectomy: an Italian, multicenter, randomized phase III trial. Ann Oncol. 2012 Mar;23(3):695-700. Epub 2011 Aug 22. [https://doi.org/10.1093/annonc/mdr354 link to original article] [https://pubmed.ncbi.nlm.nih.gov/21859900/ PubMed] NCT00054626
+
#'''ITNRC CU02:''' Cognetti F, Ruggeri EM, Felici A, Gallucci M, Muto G, Pollera CF, Massidda B, Rubagotti A, Giannarelli D, Boccardo F; Italian National Research Council. Adjuvant chemotherapy with cisplatin and gemcitabine versus chemotherapy at relapse in patients with muscle-invasive bladder cancer submitted to radical cystectomy: an Italian, multicenter, randomized phase III trial. Ann Oncol. 2012 Mar;23(3):695-700. Epub 2011 Aug 22. [https://doi.org/10.1093/annonc/mdr354 link to original article] [https://pubmed.ncbi.nlm.nih.gov/21859900/ PubMed] [https://clinicaltrials.gov/study/NCT00054626 NCT00054626]
#'''EORTC 30994:''' Sternberg CN, Skoneczna I, Kerst JM, Albers P, Fossa SD, Agerbaek M, Dumez H, de Santis M, Théodore C, Leahy MG, Chester JD, Verbaeys A, Daugaard G, Wood L, Witjes JA, de Wit R, Geoffrois L, Sengelov L, Thalmann G, Charpentier D, Rolland F, Mignot L, Sundar S, Symonds P, Graham J, Joly F, Marreaud S, Collette L, Sylvester R; [[Study_Groups#EORTC|EORTC]] Genito-Urinary Cancers Group; Groupe d'Etude des Tumeurs Urogénitales; National Cancer Research Institute Bladder Cancer Study Group; National Cancer Institute of Canada Clinical Trials Group; German Association of Urologic Oncology. Immediate versus deferred chemotherapy after radical cystectomy in patients with pT3-pT4 or N+ M0 urothelial carcinoma of the bladder (EORTC 30994): an intergroup, open-label, randomised phase 3 trial. Lancet Oncol. 2015 Jan;16(1):76-86. Epub 2014 Dec 11. [https://doi.org/10.1016/S1470-2045(14)71160-X link to original article] [https://pubmed.ncbi.nlm.nih.gov/25498218 PubMed] NCT00028756
+
#'''EORTC 30994:''' Sternberg CN, Skoneczna I, Kerst JM, Albers P, Fossa SD, Agerbaek M, Dumez H, de Santis M, Théodore C, Leahy MG, Chester JD, Verbaeys A, Daugaard G, Wood L, Witjes JA, de Wit R, Geoffrois L, Sengelov L, Thalmann G, Charpentier D, Rolland F, Mignot L, Sundar S, Symonds P, Graham J, Joly F, Marreaud S, Collette L, Sylvester R; [[Study_Groups#EORTC|EORTC]] Genito-Urinary Cancers Group; Groupe d'Etude des Tumeurs Urogénitales; National Cancer Research Institute Bladder Cancer Study Group; National Cancer Institute of Canada Clinical Trials Group; German Association of Urologic Oncology. Immediate versus deferred chemotherapy after radical cystectomy in patients with pT3-pT4 or N+ M0 urothelial carcinoma of the bladder (EORTC 30994): an intergroup, open-label, randomised phase 3 trial. Lancet Oncol. 2015 Jan;16(1):76-86. Epub 2014 Dec 11. [https://doi.org/10.1016/S1470-2045(14)71160-X link to original article] [https://pubmed.ncbi.nlm.nih.gov/25498218/ PubMed] [https://clinicaltrials.gov/study/NCT00028756 NCT00028756]
#'''IMvigor010:''' Bellmunt J, Hussain M, Gschwend JE, Albers P, Oudard S, Castellano D, Daneshmand S, Nishiyama H, Majchrowicz M, Degaonkar V, Shi Y, Mariathasan S, Grivas P, Drakaki A, O'Donnell PH, Rosenberg JE, Geynisman DM, Petrylak DP, Hoffman-Censits J, Bedke J, Kalebasty AR, Zakharia Y, van der Heijden MS, Sternberg CN, Davarpanah NN, Powles T; IMvigor010 Study Group. Adjuvant atezolizumab versus observation in muscle-invasive urothelial carcinoma (IMvigor010): a multicentre, open-label, randomised, phase 3 trial. Lancet Oncol. 2021 Apr;22(4):525-537. Epub 2021 Mar 12. [https://doi.org/10.1016/s1470-2045(21)00004-8 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc8495594/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/33721560/ PubMed] NCT02450331
 
  
 
==Placebo==
 
==Placebo==
Line 197: Line 190:
 
|1998-2003
 
|1998-2003
 
| style="background-color:#1a9851" |Phase 3 (C)
 
| style="background-color:#1a9851" |Phase 3 (C)
|[[#Fenretinide_monotherapy_77|Fenretinide]]
+
|[[#Fenretinide_monotherapy_999|Fenretinide]]
 
| style="background-color:#ffffbf" |Did not meet primary endpoint of TTR
 
| style="background-color:#ffffbf" |Did not meet primary endpoint of TTR
|-
 
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8215888/ Bajorin et al. 2021 (CheckMate 274)]
 
|2016-2020
 
| style="background-color:#1a9851" |Phase 3 (C)
 
|[[Bladder_cancer#Nivolumab_monotherapy|Nivolumab]]
 
| style="background-color:#d73027" |Inferior DFS
 
 
|-
 
|-
 
|}
 
|}
Line 210: Line 197:
 
<div class="toccolours" style="background-color:#cbd5e8">
 
<div class="toccolours" style="background-color:#cbd5e8">
 
====Preceding treatment====
 
====Preceding treatment====
*MDA-ID-95236: [[Surgery#TURBT|TURBT]]
+
*[[Surgery#TURBT|TURBT]]
*CheckMate 274: [[Surgery#Radical_cystectomy|Radical surgery]]
 
 
</div></div>
 
</div></div>
 
===References===
 
===References===
#'''MDA-ID-95236:''' Sabichi AL, Lerner SP, Atkinson EN, Grossman HB, Caraway NP, Dinney CP, Penson DF, Matin S, Kamat A, Pisters LL, Lin DW, Katz RL, Brenner DE, Hemstreet GP 3rd, Wargo M, Bleyer A, Sanders WH, Clifford JL, Parnes HL, Lippman SM. Phase III prevention trial of fenretinide in patients with resected non-muscle-invasive bladder cancer. Clin Cancer Res. 2008 Jan 1;14(1):224-9. [https://doi.org/10.1158/1078-0432.ccr-07-0733 link to original article] [https://pubmed.ncbi.nlm.nih.gov/18172274/ PubMed] NCT00004154
+
#'''MDA-ID-95236:''' Sabichi AL, Lerner SP, Atkinson EN, Grossman HB, Caraway NP, Dinney CP, Penson DF, Matin S, Kamat A, Pisters LL, Lin DW, Katz RL, Brenner DE, Hemstreet GP 3rd, Wargo M, Bleyer A, Sanders WH, Clifford JL, Parnes HL, Lippman SM. Phase III prevention trial of fenretinide in patients with resected non-muscle-invasive bladder cancer. Clin Cancer Res. 2008 Jan 1;14(1):224-9. [https://doi.org/10.1158/1078-0432.ccr-07-0733 link to original article] [https://pubmed.ncbi.nlm.nih.gov/18172274/ PubMed] [https://clinicaltrials.gov/study/NCT00004154 NCT00004154]
#'''CheckMate 274:''' Bajorin DF, Witjes JA, Gschwend JE, Schenker M, Valderrama BP, Tomita Y, Bamias A, Lebret T, Shariat SF, Park SH, Ye D, Agerbaek M, Enting D, McDermott R, Gajate P, Peer A, Milowsky MI, Nosov A, Neif Antonio J Jr, Tupikowski K, Toms L, Fischer BS, Qureshi A, Collette S, Unsal-Kacmaz K, Broughton E, Zardavas D, Koon HB, Galsky MD. Adjuvant Nivolumab versus Placebo in Muscle-Invasive Urothelial Carcinoma. N Engl J Med. 2021 Jun 3;384(22):2102-2114. [https://doi.org/10.1056/nejmoa2034442 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8215888/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/34077643/ PubMed] NCT02632409
 
##'''HRQoL analysis:''' Witjes JA, Galsky MD, Gschwend JE, Broughton E, Braverman J, Nasroulah F, Maira-Arce M, Ye X, Shi L, Guo S, Hamilton M, Bajorin DF. Health-related Quality of Life with Adjuvant Nivolumab After Radical Resection for High-risk Muscle-invasive Urothelial Carcinoma: Results from the Phase 3 CheckMate 274 Trial. Eur Urol Oncol. 2022 Oct;5(5):553-563. Epub 2022 Mar 11. [https://doi.org/10.1016/j.euo.2022.02.003 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10062393/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/35288066/ PubMed]
 
 
=Maintenance after first-line therapy=
 
=Maintenance after first-line therapy=
==Best supportive care==
 
<div class="toccolours" style="background-color:#eeeeee">
 
===Regimen===
 
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
! style="width: 17%" |Study
 
! style="width: 15%" |Dates of enrollment
 
! style="width: 17%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
! style="width: 17%" |Comparator
 
! style="width: 17%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
! style="width: 17%" |[[Levels_of_Evidence#Toxicity|Comparative Toxicity]]
 
|-
 
|[https://doi.org/10.1056/NEJMoa2002788 Powles et al. 2020 (JAVELIN Bladder 100)]
 
|2016-2019
 
| style="background-color:#1a9851" |Phase 3 (C)
 
|[[Bladder_cancer#Avelumab_monotherapy|Avelumab]]
 
| style="background-color:#d73027" |Inferior OS
 
| style="background-color:#1a9851" |Less toxic
 
|-
 
|}
 
''No further active antineoplastic treatment.''
 
<div class="toccolours" style="background-color:#cbd5e8">
 
====Preceding treatment====
 
 
*[[Bladder_cancer#Cisplatin_.26_Gemcitabine_3 | Cisplatin & Gemcitabine]] x 4 to 6 or [[Bladder_cancer#Carboplatin_.26_Gemcitabine_.28GCb.29 | Carboplatin & Gemcitabine]] x 4 to 6 cycles
 
</div></div>
 
===References===
 
#'''JAVELIN Bladder 100:''' Powles T, Park SH, Voog E, Caserta C, Valderrama BP, Gurney H, Kalofonos H, Radulović S, Demey W, Ullén A, Loriot Y, Sridhar SS, Tsuchiya N, Kopyltsov E, Sternberg CN, Bellmunt J, Aragon-Ching JB, Petrylak DP, Laliberte R, Wang J, Huang B, Davis C, Fowst C, Costa N, Blake-Haskins JA, di Pietro A, Grivas P. Avelumab Maintenance Therapy for Advanced or Metastatic Urothelial Carcinoma. N Engl J Med. 2020 Sep 24;383(13):1218-1230. Epub 2020 Sep 18. [https://doi.org/10.1056/NEJMoa2002788 link to original article] [https://pubmed.ncbi.nlm.nih.gov/32945632/ PubMed] NCT02603432
 
 
 
==Placebo==
 
==Placebo==
 
<div class="toccolours" style="background-color:#eeeeee">
 
<div class="toccolours" style="background-color:#eeeeee">
Line 259: Line 215:
 
|2007-2013
 
|2007-2013
 
| style="background-color:#1a9851" |Phase 3 (C)
 
| style="background-color:#1a9851" |Phase 3 (C)
|[[#Lapatinib_monotherapy_99|Lapatinib]]
+
|[[#Lapatinib_monotherapy_999|Lapatinib]]
 
| style="background-color:#ffffbf" |Did not meet primary endpoint of PFS
 
| style="background-color:#ffffbf" |Did not meet primary endpoint of PFS
 
|-
 
|-
Line 265: Line 221:
 
|2007-2012
 
|2007-2012
 
| style="background-color:#1a9851" |Phase 3 (C)
 
| style="background-color:#1a9851" |Phase 3 (C)
|[[#Celecoxib_monotherapy_99|Celecoxib]]
+
|[[#Celecoxib_monotherapy_999|Celecoxib]]
 
| style="background-color:#ffffbf" |Did not meet primary endpoint of TTR
 
| style="background-color:#ffffbf" |Did not meet primary endpoint of TTR
 
|-
 
|-
Line 273: Line 229:
 
===References===
 
===References===
  
#'''LaMB:''' Powles T, Huddart RA, Elliott T, Sarker SJ, Ackerman C, Jones R, Hussain S, Crabb S, Jagdev S, Chester J, Hilman S, Beresford M, Macdonald G, Santhanam S, Frew JA, Stockdale A, Hughes S, Berney D, Chowdhury S. Phase III, double-blind, randomized trial that compared maintenance lapatinib versus placebo after first-line chemotherapy in patients with human epidermal growth factor receptor 1/2-positive metastatic bladder cancer. J Clin Oncol. 2017 Jan;35(1):48-55. Epub 2016 Oct 28. [https://doi.org/10.1200/JCO.2015.66.3468 link to original article] [https://pubmed.ncbi.nlm.nih.gov/28034079 PubMed] NCT00949455
+
#'''LaMB:''' Powles T, Huddart RA, Elliott T, Sarker SJ, Ackerman C, Jones R, Hussain S, Crabb S, Jagdev S, Chester J, Hilman S, Beresford M, Macdonald G, Santhanam S, Frew JA, Stockdale A, Hughes S, Berney D, Chowdhury S. Phase III, double-blind, randomized trial that compared maintenance lapatinib versus placebo after first-line chemotherapy in patients with human epidermal growth factor receptor 1/2-positive metastatic bladder cancer. J Clin Oncol. 2017 Jan;35(1):48-55. Epub 2016 Oct 28. [https://doi.org/10.1200/JCO.2015.66.3468 link to original article] [https://pubmed.ncbi.nlm.nih.gov/28034079/ PubMed] [https://clinicaltrials.gov/study/NCT00949455 NCT00949455]
 
#'''BOXIT:''' Kelly JD, Tan WS, Porta N, Mostafid H, Huddart R, Protheroe A, Bogle R, Blazeby J, Palmer A, Cresswell J, Johnson M, Brough R, Madaan S, Andrews S, Cruickshank C, Burnett S, Maynard L, Hall E; BOXIT Investigators. BOXIT-A Randomised Phase III Placebo-controlled Trial Evaluating the Addition of Celecoxib to Standard Treatment of Transitional Cell Carcinoma of the Bladder (CRUK/07/004). Eur Urol. 2019 Apr;75(4):593-601. Epub 2018 Sep 29. [https://doi.org/10.1016/j.eururo.2018.09.020 link to original article] [https://pubmed.ncbi.nlm.nih.gov/30279015/ PubMed] ISRCTN84681538
 
#'''BOXIT:''' Kelly JD, Tan WS, Porta N, Mostafid H, Huddart R, Protheroe A, Bogle R, Blazeby J, Palmer A, Cresswell J, Johnson M, Brough R, Madaan S, Andrews S, Cruickshank C, Burnett S, Maynard L, Hall E; BOXIT Investigators. BOXIT-A Randomised Phase III Placebo-controlled Trial Evaluating the Addition of Celecoxib to Standard Treatment of Transitional Cell Carcinoma of the Bladder (CRUK/07/004). Eur Urol. 2019 Apr;75(4):593-601. Epub 2018 Sep 29. [https://doi.org/10.1016/j.eururo.2018.09.020 link to original article] [https://pubmed.ncbi.nlm.nih.gov/30279015/ PubMed] ISRCTN84681538
 
=Locally advanced or metastatic disease, subsequent lines=
 
==Best supportive care==
 
<div class="toccolours" style="background-color:#eeeeee">
 
===Regimen===
 
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
! style="width: 20%" |Study
 
! style="width: 20%" |Dates of enrollment
 
! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
! style="width: 20%" |Comparator
 
! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
|-
 
|[https://doi.org/10.1200/JCO.2008.20.5534 Bellmunt et al. 2009 (CA183004)]
 
|2003-2006
 
| style="background-color:#1a9851" |Phase 3 (C)
 
|[[Bladder_cancer#Vinflunine_monotherapy|Vinflunine]]
 
| style="background-color:#d73027" |Inferior OS<sup>1</sup>
 
|-
 
|}
 
''<sup>1</sup>Reported efficacy is based on the 2013 update.''<br>
 
''No active antineoplastic treatment.''
 
</div>
 
===References===
 
 
#'''CA183004:''' Bellmunt J, Théodore C, Demkov T, Komyakov B, Sengelov L, Daugaard G, Caty A, Carles J, Jagiello-Gruszfeld A, Karyakin O, Delgado FM, Hurteloup P, Winquist E, Morsli N, Salhi Y, Culine S, von der Maase H. Phase III trial of vinflunine plus best supportive care compared with best supportive care alone after a platinum-containing regimen in patients with advanced transitional cell carcinoma of the urothelial tract. J Clin Oncol. 2009 Sep 20;27(27):4454-61. Epub 2009 Aug 17. Erratum in: J Clin Oncol. 2010 Jan 1;28(1):182. Winquist, Eric [added]. [https://doi.org/10.1200/JCO.2008.20.5534 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/19687335/ PubMed] NCT00315237
 
##'''Update:''' Bellmunt J, Fougeray R, Rosenberg JE, von der Maase H, Schutz FA, Salhi Y, Culine S, Choueiri TK. Long-term survival results of a randomized phase III trial of vinflunine plus best supportive care versus best supportive care alone in advanced urothelial carcinoma patients after failure of platinum-based chemotherapy. Ann Oncol. 2013 Jun;24(6):1466-72. Epub 2013 Feb 17. [https://doi.org/10.1093/annonc/mdt007 link to original article] [https://pubmed.ncbi.nlm.nih.gov/23419284/ PubMed]
 
  
 
[[Category:Bladder cancer regimens]]
 
[[Category:Bladder cancer regimens]]
 
[[Category:Disease-specific pages]]
 
[[Category:Disease-specific pages]]
[[Category:Genitourinary cancers]]
+
[[Category:Urothelial carcinomas]]
 
[[Category:Null regimens]]
 
[[Category:Null regimens]]

Latest revision as of 19:48, 8 March 2024

The purpose of this page is to provide references to "null therapy" such as placebo and observation. These references provide further insight into the historical development of the treatment landscape. See the main bladder cancer page for regimens that include active anticancer treatment.


Nonmuscle invasive bladder cancer/Intravesical chemotherapy

Observation

Regimen

Study Dates of enrollment Evidence Comparator Comparative Efficacy
Ito et al. 2013 (THP Monotherapy Study Group Trial) 2005-2008 Randomized Phase 2 (C) Pirarubicin Seems to have inferior RFS

No active antineoplastic treatment after surgery.

Preceding treatment

References

  1. THP Monotherapy Study Group Trial: Ito A, Shintaku I, Satoh M, Ioritani N, Aizawa M, Tochigi T, Kawamura S, Aoki H, Numata I, Takeda A, Namiki S, Namima T, Ikeda Y, Kambe K, Kyan A, Ueno S, Orikasa K, Katoh S, Adachi H, Tokuyama S, Ishidoya S, Yamaguchi T, Arai Y. Prospective randomized phase II trial of a single early intravesical instillation of pirarubicin (THP) in the prevention of bladder recurrence after nephroureterectomy for upper urinary tract urothelial carcinoma: the THP Monotherapy Study Group Trial. J Clin Oncol. 2013 Apr 10;31(11):1422-7. Epub 2013 Mar 4. link to original article PubMed UMIN000004039

Placebo

Regimen

Study Dates of enrollment Evidence Comparator Comparative Efficacy
Messing et al. 2018 (SWOG S0337) 2008-2012 Phase 3 (C) Gemcitabine Inferior TTR

Preceding treatment

  • TURBT, up to 3 hours prior

References

  1. SWOG S0337: Messing EM, Tangen CM, Lerner SP, Sahasrabudhe DM, Koppie TM, Wood DP Jr, Mack PC, Svatek RS, Evans CP, Hafez KS, Culkin DJ, Brand TC, Karsh LI, Holzbeierlein JM, Wilson SS, Wu G, Plets M, Vogelzang NJ, Thompson IM Jr. Effect of intravesical instillation of gemcitabine vs saline immediately following resection of suspected low-grade non-muscle-invasive bladder cancer on tumor recurrence: SWOG S0337 randomized clinical trial. JAMA. 2018 May 8;319(18):1880-1888. link to original article link to PMC article PubMed NCT00445601

Neoadjuvant chemotherapy

No neoadjuvant therapy

Regimen

Study Dates of enrollment Evidence Comparator Comparative Efficacy
Martinez-Piñeiro et al. 1995 1984-1989 Phase 3 (C) Cisplatin Did not meet primary endpoint of OS
Grossman et al. 2003 (SWOG S8710) 1987-1998 Phase 3 (C) MVAC Might have inferior OS
Griffiths et al. 1999 (BA06 30894) 1989-1995 Phase 3 (C) CMV Seems to have inferior OS1
Shipley et al. 1998 (RTOG 89-03) 1990-1993 Phase 3 (C) MCV Did not meet primary endpoint of OS
Kitamura et al. 2014 (JCOG0209) 2003-2009 Phase 3 (C) MVAC Might have inferior OS

1Reported efficacy for BA06 30894 is based on the 2011 update.
No preoperative treatment.

Subsequent treatment

References

  1. Martinez-Piñeiro JA, Gonzalez Martin M, Arocena F, Flores N, Roncero CR, Portillo JA, Escudero A, Jimenez Cruz F, Isorna S. Neoadjuvant cisplatin chemotherapy before radical cystectomy in invasive transitional cell carcinoma of the bladder: a prospective randomized phase III study. J Urol. 1995 Mar;153(3 Pt 2):964-73. link to original article PubMed
  2. RTOG 89-03: Shipley WU, Winter KA, Kaufman DS, Lee WR, Heney NM, Tester WR, Donnelly BJ, Venner PM, Perez CA, Murray KJ, Doggett RS, True LD. Phase III trial of neoadjuvant chemotherapy in patients with invasive bladder cancer treated with selective bladder preservation by combined radiation therapy and chemotherapy: initial results of Radiation Therapy Oncology Group 89-03. J Clin Oncol. 1998 Nov;16(11):3576-83. link to original article PubMed
    1. Pooled update: Efstathiou JA, Bae K, Shipley WU, Kaufman DS, Hagan MP, Heney NM, Sandler HM. Late pelvic toxicity after bladder-sparing therapy in patients with invasive bladder cancer: RTOG 89-03, 95-06, 97-06, 99-06. J Clin Oncol. 2009 Sep 1;27(25):4055-61. link to original article link to PMC article PubMed
    2. Pooled update: Mak RH, Hunt D, Shipley WU, Efstathiou JA, Tester WJ, Hagan MP, Kaufman DS, Heney NM, Zietman AL. Long-Term Outcomes in Patients With Muscle-Invasive Bladder Cancer After Selective Bladder-Preserving Combined-Modality Therapy: A Pooled Analysis of Radiation Therapy Oncology Group Protocols 8802, 8903, 9506, 9706, 9906, and 0233. J Clin Oncol. 2014 Dec 1;32(34):3801-9. Epub 2014 Nov 3. link to original article link to PMC article PubMed
  3. BA06 30894: Griffiths G, Hall R, Sylvester R, Raghavan D, Parmar MK; International Collaboration of Trialists. Neoadjuvant cisplatin, methotrexate, and vinblastine chemotherapy for muscle-invasive bladder cancer: a randomised controlled trial. Lancet. 1999 Aug 14;354(9178):533-40. Erratum in: Lancet 1999 Nov 6;354(9190):1650. link to original article PubMed ISRCTN82694463
    1. Update: Griffiths G, Hall R, Sylvester R, Raghavan D, Parmar MK; International Collaboration of Trialists; Medical Research Council Advanced Bladder Cancer Working Party (now the National Cancer Research Institute Bladder Cancer Clinical Studies Group); EORTC 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. International phase III trial assessing neoadjuvant cisplatin, methotrexate, and vinblastine chemotherapy for muscle-invasive bladder cancer: long-term results of the BA06 30894 trial. J Clin Oncol. 2011 Jun 1;29(16):2171-7. Epub 2011 Apr 18. link to original article link to PMC article PubMed
  4. SWOG S8710: Grossman HB, Natale RB, Tangen CM, Speights VO, Vogelzang NJ, Trump DL, deVere White RW, Sarosdy MF, Wood DP Jr, Raghavan D, Crawford ED. Neoadjuvant chemotherapy plus cystectomy compared with cystectomy alone for locally advanced bladder cancer. N Engl J Med. 2003 Aug 28;349(9):859-66. link to original article PubMed
  5. JCOG0209: Kitamura H, Tsukamoto T, Shibata T, Masumori N, Fujimoto H, Hirao Y, Fujimoto K, Kitamura Y, Tomita Y, Tobisu K, Niwakawa M, Naito S, Eto M, Kakehi Y; Urologic Oncology Study Group of the Japan Clinical Oncology Group. Randomised phase III study of neoadjuvant chemotherapy with methotrexate, doxorubicin, vinblastine and cisplatin followed by radical cystectomy compared with radical cystectomy alone for muscle-invasive bladder cancer: Japan Clinical Oncology Group Study JCOG0209. Ann Oncol. 2014 Jun;25(6):1192-8. link to original article PubMed UMIN C000000093
  6. KEYNOTE-905: NCT03924895

Adjuvant chemotherapy

Observation

Regimen

Study Dates of enrollment Evidence Comparator Comparative Efficacy
Stadler et al. 2011 (SWOG-4B951) 1997-2006 Phase 3 (C) MVAC Did not meet primary endpoint of RFS
Paz-Ares et al 2010 (SOGUG 99/01) 2000-2007 Phase 3 (C) PGC Inferior OS
Cognetti et al. 2011 (ITNRC CU02) 2001-2007 Phase 3 (C) GC Did not meet primary endpoint of OS
Sternberg et al. 2014 (EORTC 30994) 2002-2008 Phase 3 (C) MVAC Did not meet primary endpoint of OS

Patients in SOGUG 99/01 had pT3-4 and/or pN positive disease with adequate renal function (CrCl more than 50 mL/min/1.73m2). This arm underwent cystectomy and no further treatment. The study prematurely closed due to poor recruitment and lacks adequate power to make firm conclusions.

Biomarker eligibility criteria

  • SWOG-4B951: positive p53 staining

Preceding treatment

Subsequent treatment

  • EORTC 30994, upon relapse: First-line MVAC x 6

References

  1. Abstract: L. G. Paz-Ares, E. Solsona, E. Esteban, A. Saez, J. Gonzalez-Larriba, A. Anton, M. Hevia, F. de la Rosa, V. Guillem, and J. Bellmunt. Randomized phase III trial comparing adjuvant paclitaxel/gemcitabine/cisplatin (PGC) to observation in patients with resected invasive bladder cancer: Results of the Spanish Oncology Genitourinary Group (SOGUG) 99/01 study. ASCO MEETING ABSTRACTS Jun 22, 2010:LBA4518. link to abstract
  2. SWOG-4B951: Stadler WM, Lerner SP, Groshen S, Stein JP, Shi SR, Raghavan D, Esrig D, Steinberg G, Wood D, Klotz L, Hall C, Skinner DG, Cote RJ. Phase III study of molecularly targeted adjuvant therapy in locally advanced urothelial cancer of the bladder based on p53 status. J Clin Oncol. 2011 Sep 1;29(25):3443-9. Epub 2011 Aug 1. link to original article link to PMC article PubMed NCT00005047
  3. ITNRC CU02: Cognetti F, Ruggeri EM, Felici A, Gallucci M, Muto G, Pollera CF, Massidda B, Rubagotti A, Giannarelli D, Boccardo F; Italian National Research Council. Adjuvant chemotherapy with cisplatin and gemcitabine versus chemotherapy at relapse in patients with muscle-invasive bladder cancer submitted to radical cystectomy: an Italian, multicenter, randomized phase III trial. Ann Oncol. 2012 Mar;23(3):695-700. Epub 2011 Aug 22. link to original article PubMed NCT00054626
  4. EORTC 30994: Sternberg CN, Skoneczna I, Kerst JM, Albers P, Fossa SD, Agerbaek M, Dumez H, de Santis M, Théodore C, Leahy MG, Chester JD, Verbaeys A, Daugaard G, Wood L, Witjes JA, de Wit R, Geoffrois L, Sengelov L, Thalmann G, Charpentier D, Rolland F, Mignot L, Sundar S, Symonds P, Graham J, Joly F, Marreaud S, Collette L, Sylvester R; EORTC Genito-Urinary Cancers Group; Groupe d'Etude des Tumeurs Urogénitales; National Cancer Research Institute Bladder Cancer Study Group; National Cancer Institute of Canada Clinical Trials Group; German Association of Urologic Oncology. Immediate versus deferred chemotherapy after radical cystectomy in patients with pT3-pT4 or N+ M0 urothelial carcinoma of the bladder (EORTC 30994): an intergroup, open-label, randomised phase 3 trial. Lancet Oncol. 2015 Jan;16(1):76-86. Epub 2014 Dec 11. link to original article PubMed NCT00028756

Placebo

Regimen

Study Dates of enrollment Evidence Comparator Comparative Efficacy
Sabichi et al. 2008 (MDA-ID-95236) 1998-2003 Phase 3 (C) Fenretinide Did not meet primary endpoint of TTR

No active antineoplastic therapy.

Preceding treatment

References

  1. MDA-ID-95236: Sabichi AL, Lerner SP, Atkinson EN, Grossman HB, Caraway NP, Dinney CP, Penson DF, Matin S, Kamat A, Pisters LL, Lin DW, Katz RL, Brenner DE, Hemstreet GP 3rd, Wargo M, Bleyer A, Sanders WH, Clifford JL, Parnes HL, Lippman SM. Phase III prevention trial of fenretinide in patients with resected non-muscle-invasive bladder cancer. Clin Cancer Res. 2008 Jan 1;14(1):224-9. link to original article PubMed NCT00004154

Maintenance after first-line therapy

Placebo

Regimen

Study Dates of enrollment Evidence Comparator Comparative Efficacy
Powles et al. 2016 (LaMB) 2007-2013 Phase 3 (C) Lapatinib Did not meet primary endpoint of PFS
Kelly et al. 2019 (BOXIT) 2007-2012 Phase 3 (C) Celecoxib Did not meet primary endpoint of TTR

No active antineoplastic treatment.

References

  1. LaMB: Powles T, Huddart RA, Elliott T, Sarker SJ, Ackerman C, Jones R, Hussain S, Crabb S, Jagdev S, Chester J, Hilman S, Beresford M, Macdonald G, Santhanam S, Frew JA, Stockdale A, Hughes S, Berney D, Chowdhury S. Phase III, double-blind, randomized trial that compared maintenance lapatinib versus placebo after first-line chemotherapy in patients with human epidermal growth factor receptor 1/2-positive metastatic bladder cancer. J Clin Oncol. 2017 Jan;35(1):48-55. Epub 2016 Oct 28. link to original article PubMed NCT00949455
  2. BOXIT: Kelly JD, Tan WS, Porta N, Mostafid H, Huddart R, Protheroe A, Bogle R, Blazeby J, Palmer A, Cresswell J, Johnson M, Brough R, Madaan S, Andrews S, Cruickshank C, Burnett S, Maynard L, Hall E; BOXIT Investigators. BOXIT-A Randomised Phase III Placebo-controlled Trial Evaluating the Addition of Celecoxib to Standard Treatment of Transitional Cell Carcinoma of the Bladder (CRUK/07/004). Eur Urol. 2019 Apr;75(4):593-601. Epub 2018 Sep 29. link to original article PubMed ISRCTN84681538