Bladder cancer
Page editor | Section editor | ||
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Michael J. Glover, MD Stanford University Palo Alto, CA, USA |
Ali Raza Khaki, MD Stanford University Palo Alto, CA, USA |
Are you looking for a regimen but can't find it here? It is possible that we've moved it to the historical regimens page. For placebo or observational studies in this condition, please visit this page. If you still can't find it, please let us know so we can add it!.
Note: much of the content that was previously on this page has recently been moved to the Urothelial carcinoma page to reflect the fact that many regimens, especially for metastatic disease, are generic to urothelial cancer. This page has regimens specific to bladder cancer.
25 regimens on this page
45 variants on this page
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Guidelines
Given the rapid change in evidence in many areas of hematology/oncology, readers are encouraged to consider any article published 5+ years ago to be for historical purposes, only.
AUA, ASCO, ASTRO, SUO
- 2017: Chang et al. Treatment of non-metastatic muscle-invasive bladder cancer: AUA/ASCO/ASTRO/SUO Guideline PubMed
EAU-ESMO
- 2019: Horwich et al. EAU–ESMO consensus statements on the management of advanced and variant bladder cancer—an international collaborative multi-stakeholder effort: under the auspices of the EAU and ESMO Guidelines Committees PubMed
ESMO
- 2022: Powles et al. Bladder cancer: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up PubMed
- 2014: Bellmunt et al. Bladder cancer: ESMO Clinical Practice Guidelines PubMed
- 2011: Bellmunt et al. Bladder cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up PubMed
- 2010: Bellmunt et al. Bladder cancer: ESMO Practice Guidelines for diagnosis, treatment and follow-up PubMed
- 2009: Bellmunt et al. Invasive bladder cancer: ESMO clinical recommendations for diagnosis, treatment and follow-up PubMed
- 2008: Bellmunt et al. Invasive bladder cancer: ESMO clinical recommendations for diagnosis, treatment and follow-up PubMed
- 2007: Bellmunt & Albiol. Invasive bladder cancer: ESMO clinical recommendations for diagnosis, treatment and follow-up PubMed
- 2005: Kataja & Pavlidis. ESMO Minimum Clinical Recommendations for diagnosis, treatment and follow-up of invasive bladder cancer PubMed
- 2003: Sengeløv. ESMO Minimum Clinical Recommendations for diagnosis, treatment and follow-up of invasive bladder cancer PubMed
NCCN
- 2020: Flaig et al. Bladder Cancer, Version 3.2020, NCCN Clinical Practice Guidelines in Oncology. PubMed
- 2017: Spiess et al. Bladder Cancer, Version 5.2017, NCCN Clinical Practice Guidelines in Oncology PubMed
- 2013: Clark et al. Bladder cancer. PubMed
- 2009: Montie et al. Bladder cancer PubMed
- 2006: Montie et al. Bladder cancer. Clinical guidelines in oncology. PubMed
- 2005: Montie et al. Bladder cancer. Clinical practice guidelines in oncology. PubMed
Nonmuscle invasive bladder cancer
BCG vaccine monotherapy
AIM pathway regimen 2022-08-01 |
Regimen variant #1, low-dose (27 mg)
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Ojea et al. 2007 (CUETO study 95011) | 1995-1998 | Phase 3 (E-esc) | 1. Mitomycin | Superior DFS (primary endpoint) |
2. BCG; very-low-dose | Did not meet primary endpoint of DFS |
Preceding treatment
- TURBT, within 14 to 21 days
Immunotherapy
- Bacillus Calmette-Guérin (Connaught strain) as follows:
- Cycle 1: 27 mg intravesicularly once per day on days 1, 8, 15, 22, 29, 36
- Cycles 2 to 7: 27 mg intravesicularly once on day 1
42-day course, then 14 day cycles for 6 cycles
Regimen variant #2, intravesical (81 mg) & percutaneous, with maintenance therapy
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Lamm et al. 2000 (SWOG 8507) | 1985-1988 | Phase 3 (E-RT-esc) | BCG; Intravesical & percutaneous BCG, without maintenance therapy | Superior RFS |
Immunotherapy, induction
- Bacillus Calmette-Guérin (Connaught strain) 81 mg in 50.5 mL saline suspension is created and administered as follows:
- 50 mL (~80.2 mg) intravesicularly, and delivered through a catheter into the bladder once per day on days 1, 8, 15, 22, 29, 36. Patients lie on their abdomen for 15 minutes and retain the BCG suspension for up to 2 hours if possible.
- 0.5 mL (~0.8 mg) applied once per day on days 1, 8, 15, 22, 29, 36 to the inner thigh, which is first cleaned with alcohol. For percutaneous administration, the skin is punctured 3 times with a sterile 28 gauge needle. Each subsequent administration alternates between thighs (i.e. left thigh on one week, right thigh the next week, left thigh the week after, etc.).
6-week course, then proceed to maintenance therapy
Immunotherapy, maintenance
The authors were a bit unclear about the schedule of maintenance therapy. This is our best interpretation of how the schedule was described.
- Bacillus Calmette-Guérin (Connaught strain) 81 mg in 50.5 mL saline suspension is created and administered as follows:
- 50 mL (~80.2 mg) intravesicularly, and delivered through a catheter into the bladder once per day on days 1, 8, 15. Patients lie on their abdomen for 15 minutes and retain the BCG suspension for up to 2 hours if possible.
- 0.5 mL (~0.8 mg) applied once per day on days 1, 8, 15 to the inner thigh, which is first cleaned with alcohol. For percutaneous administration, the skin is punctured 3 times with a sterile 28 gauge needle. Each subsequent administration alternates between thighs (i.e. left thigh on one week, right thigh the next week, left thigh the week after, etc.).
3-week courses; each course is given at 3 months, 6 months, 12 months, 18 months, 24 months, 30 months, and 36 months after the start of induction therapy
Regimen variant #3, intravesical (81 mg) & percutaneous, without maintenance therapy
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Lamm et al. 2000 (SWOG 8507) | 1985-1988 | Phase 3 (C) | BCG; Intravesical & percutaneous BCG, with maintenance therapy | Inferior RFS |
Immunotherapy
- Bacillus Calmette-Guérin (Connaught strain) 81 mg in 50.5 mL saline suspension is created and administered as follows:
- 50 mL (~80.2 mg) intravesicularly, and delivered through a catheter into the bladder once per day on days 1, 8, 15, 22, 29, 36. Patients lie on their abdomen for 15 minutes and retain the BCG suspension for up to 2 hours if possible.
- 0.5 mL (~0.8 mg) applied once per day on days 1, 8, 15, 22, 29, 36 to the inner thigh, which is first cleaned with alcohol. For percutaneous administration, the skin is punctured 3 times with a sterile 28 gauge needle. Each subsequent administration alternates between thighs (i.e. left thigh on one week, right thigh the next week, left thigh the week after, etc.).
6-week course
Regimen variant #4, intravesical (120 mg) & percutaneous, with maintenance therapy
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Lamm et al. 1991 (SWOG 8216) | 1983-1985 | Phase 3 (E-RT-switch-ooc) | Doxorubicin | Seems to have superior DFS |
Immunotherapy, induction
- Bacillus Calmette-Guérin (Connaught strain) 120 mg (3 vials) in 50.5 mL saline suspension is created and administered as follows:
- 50 mL (~120 mg) intravesicularly, and delivered through a catheter into the bladder once per day on days 1, 8, 15, 22, 29, 36. Patients retain the BCG suspension for up to 2 hours if possible.
- 0.5 mL (~1.2 mg) applied once per day on days 1, 8, 15, 22, 29, 36 to the upper part of the inner thigh
6-week course, then proceed to maintenance therapy
Immunotherapy, maintenance
- Bacillus Calmette-Guérin (Connaught strain) 120 mg (3 vials) in 50.5 mL saline suspension is created and administered as follows:
- 50 mL (~120 mg) intravesicularly once on day 1. Patients retain the BCG suspension for up to 2 hours if possible.
- 0.5 mL (~1.2 mg) applied once on day 1 to the upper part of the inner thigh
Given at 3 months, 6 months, 12 months, 18 months, and 24 months
Regimen variant #5, 150 mg
Historic variant |
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Martínez-Piñeiro et al. 1990 | 1980-1988 | Phase 3 (E-switch-ooc) | 1. Doxorubicin 2. Thiotepa |
Superior RFS |
Note: details are very sparse in the abstract and this variant is probably only of historic interest.
Immunotherapy
- BCG vaccine 150 mg intravesicularly x 15 treatments
References
- Martínez-Piñeiro JA, Jiménez León J, Martínez-Piñeiro L Jr, Fiter L, Mosteiro JA, Navarro J, García Matres MJ, Cárcamo P. Bacillus Calmette-Guérin versus doxorubicin versus thiotepa: a randomized prospective study in 202 patients with superficial bladder cancer. J Urol. 1990 Mar;143(3):502-6. link to original article contains partial protocol PubMed
- SWOG 8216: Lamm DL, Blumenstein BA, Crawford ED, Montie JE, Scardino P, Grossman HB, Stanisic TH, Smith JA Jr, Sullivan J, Sarosdy MF, Crissman JD, Coltman CA. A randomized trial of intravesical doxorubicin and immunotherapy with bacille Calmette-Guérin for transitional-cell carcinoma of the bladder. N Engl J Med. 1991 Oct 24;325(17):1205-9. link to original article PubMed
- SWOG 8507: Lamm DL, Blumenstein BA, Crissman JD, Montie JE, Gottesman JE, Lowe BA, Sarosdy MF, Bohl RD, Grossman HB, Beck TM, Leimert JT, Crawford ED. Maintenance bacillus Calmette-Guérin immunotherapy for recurrent TA, T1 and carcinoma in situ transitional cell carcinoma of the bladder: a randomized Southwest Oncology Group Study. J Urol. 2000 Apr;163(4):1124-9. link to original article contains dosing details in manuscript PubMed
- Meta-analysis: Sylvester RJ, van der Meijden AP, Lamm DL. Intravesical bacillus Calmette-Guérin reduces the risk of progression in patients with superficial bladder cancer: a meta-analysis of the published results of randomized clinical trials. J Urol. 2002 Nov;168(5):1964-70. link to original article PubMed
- CUETO study 95011: Ojea A, Nogueira JL, Solsona E, Flores N, Gómez JM, Molina JR, Chantada V, Camacho JE, Piñeiro LM, Rodríguez RH, Isorna S, Blas M, Martínez-Piñeiro JA, Madero R; CUETO. A multicentre, randomised prospective trial comparing three intravesical adjuvant therapies for intermediate-risk superficial bladder cancer: low-dose bacillus Calmette-Guérin (27 mg) versus very low-dose bacillus Calmette-Guérin (13.5 mg) versus mitomycin C. Eur Urol. 2007 Nov;52(5):1398-406. Epub 2007 Apr 27. link to original article contains dosing details in manuscript PubMed
Intravesicular Gemcitabine monotherapy
Regimen variant #1, 1 treatment
AIM pathway regimen 2022-08-01 |
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Messing et al. 2018 (SWOG S0337) | 2008-2012 | Phase 3 (E-esc) | Placebo (saline) | Superior TTR (primary endpoint) |
Preceding treatment
- TURBT, up to 3 hours prior
Chemotherapy
- Gemcitabine (Gemzar) 2000 mg in 100 mL of saline instilled intravesicularly for up to 60 minutes
One treatment
Regimen variant #2, 6 treatments
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Addeo et al. 2009 | 2003-2005 | Phase 3 (E-switch-ic) | Mitomycin | Superior DFS (co-primary endpoint) |
Chemotherapy
- Gemcitabine (Gemzar) 2000 mg in 50 mL of saline instilled intravesicularly for up to 60 minutes once per day on days 1, 8, 15, 22, 29, 36
6-week course
References
- Addeo R, Caraglia M, Bellini S, Abbruzzese A, Vincenzi B, Montella L, Miragliuolo A, Guarrasi R, Lanna M, Cennamo G, Faiola V, Del Prete S. Randomized phase III trial on gemcitabine versus mytomicin in recurrent superficial bladder cancer: evaluation of efficacy and tolerance. J Clin Oncol. 2010 Feb 1;28(4):543-8. Epub 2009 Oct 19. link to original article contains dosing details in manuscript PubMed
- 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 contains dosing details in manuscript link to PMC article PubMed NCT00445601
Intravesicular Mitomycin monotherapy
Regimen variant #1, 30 mg x 12
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Ojea et al. 2007 (CUETO study 95011) | 1995-1998 | Phase 3 (C) | 1. BCG; low-dose | Inferior DFS |
2. BCG; very-low-dose | Did not meet efficacy endpoints |
Preceding treatment
- TURBT, 14 to 21 days prior
Chemotherapy
- Mitomycin (Mutamycin) as follows:
- Cycles 1 to 3: 30 mg intravesicularly once per day on days 1 & 8
- Cycles 4 to 9: 30 mg intravesicularly once on day 1
14-day cycle for 9 cycles
Regimen variant #2, 40 mg x 11
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Lammers et al. 2012 | 2003-2007 | Phase 3 (C) | KLH | Superior RFS |
Preceding treatment
Chemotherapy
- Mitomycin (Mutamycin) 40 mg intravesicularly once on day 1
7-day cycle for 4 cycles, then monthly cycle for 4 cycles, then 3-month cycle for 3 cycles
References
- CUETO study 95011: Ojea A, Nogueira JL, Solsona E, Flores N, Gómez JM, Molina JR, Chantada V, Camacho JE, Piñeiro LM, Rodríguez RH, Isorna S, Blas M, Martínez-Piñeiro JA, Madero R; CUETO. A multicentre, randomised prospective trial comparing three intravesical adjuvant therapies for intermediate-risk superficial bladder cancer: low-dose bacillus Calmette-Guérin (27 mg) versus very low-dose bacillus Calmette-Guérin (13.5 mg) versus mitomycin C. Eur Urol. 2007 Nov;52(5):1398-406. Epub 2007 Apr 27. link to original article contains dosing details in manuscript PubMed
- Lammers RJ, Witjes WP, Janzing-Pastors MH, Caris CT, Witjes JA. Intracutaneous and intravesical immunotherapy with keyhole limpet hemocyanin compared with intravesical mitomycin in patients with non-muscle-invasive bladder cancer: results from a prospective randomized phase III trial. J Clin Oncol. 2012 Jun 20;30(18):2273-9. Epub 2012 May 14. link to original article contains dosing details in manuscript PubMed
Nadofaragene firadenovec monotherapy
Regimen
Study | Dates of enrollment | Evidence |
---|---|---|
Boorjian et al. 2020 (rAd-IFN-CS-003) | 2016-2019 | Non-randomized (RT) |
Immunotherapy
- Nadofaragene firadenovec (Adstiladrin) 75 mL intravesicularly once on day 1
3-month cycle for 4 cycles
References
- rAd-IFN-CS-003: Boorjian SA, Alemozaffar M, Konety BR, Shore ND, Gomella LG, Kamat AM, Bivalacqua TJ, Montgomery JS, Lerner SP, Busby JE, Poch M, Crispen PL, Steinberg GD, Schuckman AK, Downs TM, Svatek RS, Mashni J Jr, Lane BR, Guzzo TJ, Bratslavsky G, Karsh LI, Woods ME, Brown G, Canter D, Luchey A, Lotan Y, Krupski T, Inman BA, Williams MB, Cookson MS, Keegan KA, Andriole GL Jr, Sankin AI, Boyd A, O'Donnell MA, Sawutz D, Philipson R, Coll R, Narayan VM, Treasure FP, Yla-Herttuala S, Parker NR, Dinney CPN. Intravesical nadofaragene firadenovec gene therapy for BCG-unresponsive non-muscle-invasive bladder cancer: a single-arm, open-label, repeat-dose clinical trial. Lancet Oncol. 2021 Jan;22(1):107-117. Epub 2020 Nov 27. link to original article link to PMC article PubMed NCT02773849
Pembrolizumab monotherapy
Regimen
Study | Dates of enrollment | Evidence |
---|---|---|
Balar et al. 2021 (KEYNOTE-057) | 2015-2018 | Phase 2 (RT) |
References
- KEYNOTE-057: Balar AV, Kamat AM, Kulkarni GS, Uchio EM, Boormans JL, Roumiguié M, Krieger LEM, Singer EA, Bajorin DF, Grivas P, Seo HK, Nishiyama H, Konety BR, Li H, Nam K, Kapadia E, Frenkl T, de Wit R. Pembrolizumab monotherapy for the treatment of high-risk non-muscle-invasive bladder cancer unresponsive to BCG (KEYNOTE-057): an open-label, single-arm, multicentre, phase 2 study. Lancet Oncol. 2021 Jul;22(7):919-930. Epub 2021 May 26. Erratum in: Lancet Oncol. 2021 Aug;22(8):e347. link to original article contains dosing details in abstract PubMed NCT02625961
Intravesicular Valrubicin monotherapy
Regimen
FDA-recommended dose |
Study | Dates of enrollment | Evidence |
---|---|---|
Steinberg et al. 2000 | 1993-1996 | Non-randomized (RT) |
Chemotherapy
- Valrubicin (Valstar) 800 mg intravesicularly once per day on days 1, 8, 15, 22, 29, 36
6-week course
References
- Steinberg G, Bahnson R, Brosman S, Middleton R, Wajsman Z, Wehle M; Valrubicin Study Group. Efficacy and safety of valrubicin for the treatment of Bacillus Calmette-Guérin refractory carcinoma in situ of the bladder. J Urol. 2000 Mar;163(3):761-7. Erratum in: J Urol. 2008 Jan;179(1):386. link to original article contains dosing details in abstract PubMed
Neoadjuvant chemotherapy
Cisplatin & Gemcitabine (GC)
GC: Gemcitabine, Cisplatin
Regimen variant #1, 70/2000; single-dose cisplatin
AIM pathway regimen 2022-08-01 |
Study | Evidence |
---|---|
Dash et al. 2008 | Retrospective |
Chemotherapy
- Cisplatin (Platinol) 70 mg/m2 IV once on day 1
- Gemcitabine (Gemzar) 1000 mg/m2 IV once per day on days 1 & 8
21-day cycle for 4 cycles
Subsequent treatment
Regimen variant #2, 70/2000; split-dose cisplatin
AIM pathway regimen 2022-08-01 |
Study | Evidence |
---|---|
Dash et al. 2008 | Retrospective |
Chemotherapy
- Cisplatin (Platinol) 35 mg/m2 IV once per day on days 1 & 8
- Gemcitabine (Gemzar) 1000 mg/m2 IV once per day on days 1 & 8
21-day cycle for 4 cycles
Subsequent treatment
Regimen variant #3, 70/2500
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Pfister et al. 2022 (GETUG-AFU V05 VESPER) | 2013-2018 | Phase 3 (C) | ddMVAC x 6 | Might have inferior PFS |
Chemotherapy
- Cisplatin (Platinol) 70 mg/m2 IV once per day on day 1
- Gemcitabine (Gemzar) 1250 mg/m2 IV once per day on days 1 & 8
21-day cycle for 4 cycles
Supportive therapy
- Filgrastim (Neupogen) 5 mcg/kg SC once per day from day 3 to day 7 if febrile neutropenia or if cycle shift 7 or more days due to neutropenia in a prior cycle.
- Antiemetics used included:
Subsequent treatment
- Cystectomy to be performed up to 8 weeks after completion of chemotherapy
References
- Retrospective: Dash A, Pettus JA 4th, Herr HW, Bochner BH, Dalbagni G, Donat SM, Russo P, Boyle MG, Milowsky MI, Bajorin DF. A role for neoadjuvant gemcitabine plus cisplatin in muscle-invasive urothelial carcinoma of the bladder: a retrospective experience. Cancer. 2008 Nov 1;113(9):2471-7. link to PMC article contains dosing details in manuscript PubMed
- GETUG-AFU V05 VESPER: Pfister C, Gravis G, Fléchon A, Chevreau C, Mahammedi H, Laguerre B, Guillot A, Joly F, Soulié M, Allory Y, Harter V, Culine S; VESPER Trial Investigators. Dose-Dense Methotrexate, Vinblastine, Doxorubicin, and Cisplatin or Gemcitabine and Cisplatin as Perioperative Chemotherapy for Patients With Nonmetastatic Muscle-Invasive Bladder Cancer: Results of the GETUG-AFU V05 VESPER Trial. J Clin Oncol. 2022 Jun 20;40(18):2013-2022. Epub 2022 Mar 7. link to original article contains dosing details in manuscript PubMed NCT01812369
- KEYNOTE-B15: NCT04700124
- KEYNOTE-866: NCT03924856
Cisplatin & Gemcitabine (GC) & Pembrolizumab
GC & Pembrolizumab: Gemcitabine, Cisplatin, Pembrolizumab
Regimen
Study | Dates of enrollment | Evidence |
---|---|---|
Rose et al. 2021 (LCCC 1520) | 2016-2020 | Phase 2 |
Chemotherapy
- Cisplatin (Platinol) 35 mg/m2 IV once per day on days 1 & 8
- Gemcitabine (Gemzar) 1000 mg/m2 IV once per day on days 1 & 8
Immunotherapy
- Pembrolizumab (Keytruda) 200 mg IV once on day 1
21-day cycle for 4 cycles
Subsequent treatment
References
- LCCC 1520: Rose TL, Harrison MR, Deal AM, Ramalingam S, Whang YE, Brower B, Dunn M, Osterman CK, Heiling HM, Bjurlin MA, Smith AB, Nielsen ME, Tan HJ, Wallen E, Woods ME, George D, Zhang T, Drier A, Kim WY, Milowsky MI. Phase II Study of Gemcitabine and Split-Dose Cisplatin Plus Pembrolizumab as Neoadjuvant Therapy Before Radical Cystectomy in Patients With Muscle-Invasive Bladder Cancer. J Clin Oncol. 2021 Oct 1;39(28):3140-3148. Epub 2021 Aug 24. link to original article contains dosing details in abstract link to PMC article PubMed NCT02690558
- KEYNOTE-866: NCT03924856
MCV
MCV: Methotrexate, Cisplatin, Vinblastine
CMV: Cisplatin, Methotrexate, Vinblastine
Regimen variant #1, 2 cycles
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Kaufman et al. 1993 | NR | Phase 2 | ||
Tester et al. 1996 (RTOG 88-02) | 1988-1990 | Phase 2 | ||
Shipley et al. 1998 (RTOG 89-03) | 1990-1993 | Phase 3 (E-esc) | No neoadjuvant chemotherapy | Did not meet primary endpoint of OS |
Chemotherapy
- Methotrexate (MTX) 30 mg/m2 IV once per day on days 1, 15, 22
- Cisplatin (Platinol) 70 mg/m2 IV once on day 2
- Vinblastine (Velban) 3 mg/m2 IV once per day on days 2, 15, 22
28-day cycle for 2 cycles
Subsequent treatment
- Kaufman et al. 1993, CR: Cisplatin & RT consolidation
- RTOG 88-02 & RTOG 89-03: Cisplatin & RT induction
Regimen variant #2, 3 cycles
AIM pathway regimen 2022-08-01 |
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Griffiths et al. 1999 (BA06 30894) | 1989-1995 | Phase 3 (E-esc) | No neoadjuvant therapy | Seems to have superior OS1 (primary endpoint) Median OS: 44 vs 37 mo (HR 0.84, 95% CI 0.72-0.99) |
Zapatero et al. 2000 | 1989-1997 | Non-randomized |
1Reported efficacy for BA06 30894 is based on the 2011 update.
Eligibility criteria
- Zapatero et al. 2000: T2 to T4 Nx M0 disease
Chemotherapy
- Methotrexate (MTX) 30 mg/m2 IV bolus once per day on days 1 & 8
- Cisplatin (Platinol) 100 mg/m2 IV once on day 2, before hydration
- Vinblastine (Velban) 4 mg/m2 IV bolus once per day on days 1 & 8
Supportive therapy
- BA06 30894: Leucovorin (Folinic acid) 15 mg/m2 IV or PO every 6 hours on days 2 & 9, given after hydration, with the first dose 24 hours after the previous day's dose of methotrexate (total dose per cycle: 120 mg/m2)
21-day cycle for 3 cycles
Subsequent treatment
- Zapatero et al. 2000: after 3 cycles of chemotherapy, patients underwent cystoscopy, biopsy, and abdominal CT
- Zapatero et al. 2000, patients with CR or who were not surgical candidates: RT consolidation which begins 4 to 6 weeks after completion of chemotherapy
- Zapatero et al. 2000, patients without CR who were surgical candidates: cystectomy
References
- Kaufman DS, Shipley WU, Griffin PP, Heney NM, Althausen AF, Efird JT. Selective bladder preservation by combination treatment of invasive bladder cancer. N Engl J Med. 1993 Nov 4;329(19):1377-82. link to original article contains dosing details in manuscript PubMed
- RTOG 88-02: Tester W, Caplan R, Heaney J, Venner P, Whittington R, Byhardt R, True L, Shipley W. Neoadjuvant combined modality program with selective organ preservation for invasive bladder cancer: results of Radiation Therapy Oncology Group phase II trial 8802. J Clin Oncol. 1996 Jan;14(1):119-26. link to original article contains dosing details in manuscript 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. link to original article contains dosing details in manuscript 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. Epub 2009 Jul 27. link to original article link to PMC article 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. link to original article contains dosing details in manuscript link to PMC article PubMed
- BA06 30894: Griffiths G, Hall R, Sylvester R, Raghavan D, Parmar MK; CUETO; 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
- 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 contains dosing details in manuscript link to PMC article PubMed
- Zapatero A, Martín de Vidales C, Marín A, Cerezo L, Arellano R, Rabadán M, Pérez-Torrubia A. Invasive bladder cancer: a single-institution experience with bladder-sparing approach. Int J Cancer. 2000 Oct 20;90(5):287-94. link to original article contains dosing details in manuscript PubMed
- Update: Zapatero A, Martín de Vidales C, Arellano R, Bocardo G, Pérez M, Ríos P. Updated results of bladder-sparing trimodality approach for invasive bladder cancer. Urol Oncol. 2010 Jul-Aug;28(4):368-74. Epub 2009 Apr 11. link to original article contains dosing details in manuscript PubMed
- Update: Zapatero A, Martín de Vidales C, Arellano R, Ibañez Y, Bocardo G, Perez M, Rabadan M, García Vicente F, Cruz Conde JA, Olivier C. Long-term results of two prospective bladder-sparing trimodality approaches for invasive bladder cancer: neoadjuvant chemotherapy and concurrent radio-chemotherapy. Urology. 2012 Nov;80(5):1056-62. Epub 2012 Sep 19. link to original article PubMed
MVAC
MVAC: Methotrexate, Vinblastine, Adriamycin (Doxorubicin), Cisplatin
Regimen variant #1, 2 cycles
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Kitamura et al. 2014 (JCOG0209) | 2003-2009 | Phase 3 (E-esc) | No neoadjuvant therapy | Might have superior OS (primary endpoint) Median OS: 102 vs 82 mo (HR 0.65, 99.99% CI 0.19-2.18) |
Chemotherapy
- Methotrexate (MTX) 30 mg/m2 IV once per day on days 1, 15, 22
- Vinblastine (Velban) 3 mg/m2 IV once per day on days 2, 15, 22
- Doxorubicin (Adriamycin) 30 mg/m2 IV once on day 2
- Cisplatin (Platinol) 70 mg/m2 IV once on day 2
28-day cycle for 2 cycles
Subsequent treatment
Regimen variant #2, 3 cycles
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Grossman et al. 2003 (SWOG S8710) | 1987-1998 | Phase 3 (E-esc) | No neoadjuvant therapy | Might have superior OS (primary endpoint) |
Chemotherapy
- Methotrexate (MTX) 30 mg/m2 IV once per day on days 1, 15, 22
- Vinblastine (Velban) 3 mg/m2 IV once per day on days 2, 15, 22
- Doxorubicin (Adriamycin) 30 mg/m2 IV once on day 2
- Cisplatin (Platinol) 70 mg/m2 IV once on day 2
28-day cycle for 3 cycles
Subsequent treatment
References
- 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 contains dosing details in manuscript 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. Epub 2014 Mar 24. link to original article PubMed UMIN C000000093
- HRQoL analysis: Kitamura H, Hinotsu S, Tsukamoto T, Shibata T, Mizusawa J, Kobayashi T, Miyake M, Nishiyama N, Kojima T, Nishiyama H; Urologic Oncology Study Group of the Japan Clinical Oncology Group. Effect of neoadjuvant chemotherapy on health-related quality of life in patients with muscle-invasive bladder cancer: results from JCOG0209, a randomized phase III study. Jpn J Clin Oncol. 2020 Dec 16;50(12):1464-1469. link to original article PubMed
MVAC, dose-dense
ddMVAC: dose-dense Methotrexate, Vinblastine, Adriamycin (Doxorubicin), Cisplatin
AMVAC: Accelerated Methotrexate, Vinblastine, Adriamycin (Doxorubicin), Cisplatin
Regimen variant #1 (AMVAC), 3 cycles
Study | Dates of enrollment | Evidence |
---|---|---|
Plimack et al. 2014 (FER-GU-026) | 2009-2012 | Phase 2 |
Chemotherapy
- Methotrexate (MTX) 30 mg/m2 IV over 30 minutes once on day 1
- Vinblastine (Velban) 3 mg/m2 IV push once on day 1
- Doxorubicin (Adriamycin) 30 mg/m2 IV push once on day 1
- Cisplatin (Platinol) by the following renal function-based criteria:
- CrCl 60 mL/min/1.73m2 or more: 70 mg/m2 IV once on day 1
- CrCl less than 60 mL/min/1.73m2, at physician discretion: 35 mg/m2 IV once per day on days 1 & 2
Supportive therapy
- Pegfilgrastim (Neulasta) 6 mg SC once, 24 to 48 hours after completion of chemotherapy
- Antiemetics used included Aprepitant (Emend), Ondansetron (Zofran), and Methylprednisolone (Solumedrol).
14-day cycle for 3 cycles
Subsequent treatment
- Radical cystectomy with bilateral lymphadenectomy, within 4 to 8 weeks after the last cycle of chemotherapy
Regimen variant #2 (ddMVAC), 4 cycles
Study | Dates of enrollment | Evidence |
---|---|---|
Choueiri et al. 2014 (DFCI 08-208) | 2008-2012 | Phase 2 |
Chemotherapy
- Methotrexate (MTX) 30 mg/m2 IV over 30 minutes once on day 1
- Vinblastine (Velban) 3 mg/m2 IV push once on day 2
- Doxorubicin (Adriamycin) 30 mg/m2 IV push once on day 2
- Cisplatin (Platinol) 70 mg/m2 IV once on day 2
Supportive therapy
- Pegfilgrastim (Neulasta) 6 mg SC once on day 3 (approximately 24 hours after day 2 chemotherapy)
14-day cycle for 4 cycles
Subsequent treatment
- Cystectomy to be performed 4 to 10 weeks after completion of chemotherapy
Regimen variant #3 (ddMVAC), 6 cycles
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Pfister et al. 2022 (GETUG-AFU V05 VESPER) | 2013-2018 | Phase 3 (E-esc) | Cisplatin and Gemcitabine (GC) | Might have superior PFS (primary endpoint) PFS36: 64% vs 56% (HR 0.77, 95% CI 0.57-1.02) |
Chemotherapy
- Methotrexate (MTX) 30 mg/m2 IV over 30 minutes once on day 1
- Vinblastine (Velban) 3 mg/m2 IV push once on day 2
- Doxorubicin (Adriamycin) 30 mg/m2 IV push once on day 2
- Cisplatin (Platinol) 70 mg/m2 IV once on day 2
Supportive therapy
- Filgrastim (Neupogen) 5 mcg/kg/ day as a subcutaneous injection from day 3 to day 9
- Antiemetics used often included Aprepitant (Emend), Ondansetron (Zofran), and Dexamethasone (Decadron) but were not specified by the trial.
14-day cycle for 6 cycles
Subsequent treatment
- Cystectomy to be performed 4 to 10 weeks after completion of chemotherapy
References
- DFCI 08-208: Choueiri TK, Jacobus S, Bellmunt J, Qu A, Appleman LJ, Tretter C, Bubley GJ, Stack EC, Signoretti S, Walsh M, Steele G, Hirsch M, Sweeney CJ, Taplin ME, Kibel AS, Krajewski KM, Kantoff PW, Ross RW, Rosenberg JE. Neoadjuvant dose-dense methotrexate, vinblastine, doxorubicin, and cisplatin with pegfilgrastim support in muscle-invasive urothelial cancer: pathologic, radiologic, and biomarker correlates. J Clin Oncol. 2014 Jun 20;32(18):1889-94. Epub 2014 May 12. link to original article contains dosing details in manuscript link to PMC article PubMed NCT00808639
- FER-GU-026: Plimack ER, Hoffman-Censits JH, Viterbo R, Trabulsi EJ, Ross EA, Greenberg RE, Chen DY, Lallas CD, Wong YN, Lin J, Kutikov A, Dotan E, Brennan TA, Palma N, Dulaimi E, Mehrazin R, Boorjian SA, Kelly WK, Uzzo RG, Hudes GR. Accelerated methotrexate, vinblastine, doxorubicin, and cisplatin is safe, effective, and efficient neoadjuvant treatment for muscle-invasive bladder cancer: results of a multicenter phase II study with molecular correlates of response and toxicity. J Clin Oncol. 2014 Jun 20;32(18):1895-901. Epub 2014 May 12. link to original article contains dosing details in manuscript link to PMC article PubMed NCT01031420
- GETUG-AFU V05 VESPER: Pfister C, Gravis G, Fléchon A, Chevreau C, Mahammedi H, Laguerre B, Guillot A, Joly F, Soulié M, Allory Y, Harter V, Culine S; VESPER Trial Investigators. Dose-Dense Methotrexate, Vinblastine, Doxorubicin, and Cisplatin or Gemcitabine and Cisplatin as Perioperative Chemotherapy for Patients With Nonmetastatic Muscle-Invasive Bladder Cancer: Results of the GETUG-AFU V05 VESPER Trial. J Clin Oncol. 2022 Jun 20;40(18):2013-2022. Epub 2022 Mar 7. link to original article contains dosing details in manuscript PubMed NCT01812369
Pembrolizumab monotherapy
Regimen
Study | Dates of enrollment | Evidence |
---|---|---|
Necchi et al. 2018 (PURE-01) | 2017-2018 | Phase 2 |
Subsequent treatment
- Radical cystectomy, within 1 to 3 weeks after the last cycle of chemotherapy
References
- PURE-01: Necchi A, Anichini A, Raggi D, Briganti A, Massa S, Lucianò R, Colecchia M, Giannatempo P, Mortarini R, Bianchi M, Farè E, Monopoli F, Colombo R, Gallina A, Salonia A, Messina A, Ali SM, Madison R, Ross JS, Chung JH, Salvioni R, Mariani L, Montorsi F. Pembrolizumab as Neoadjuvant Therapy Before Radical Cystectomy in Patients With Muscle-Invasive Urothelial Bladder Carcinoma (PURE-01): An Open-Label, Single-Arm, Phase II Study. J Clin Oncol. 2018 Oct 20. Link to original article contains dosing details in manuscript PubMed NCT02736266
- Update: Necchi A, Raggi D, Gallina A, Madison R, Colecchia M, Lucianò R, Montironi R, Giannatempo P, Farè E, Pederzoli F, Bandini M, Bianchi M, Colombo R, Gandaglia G, Fossati N, Marandino L, Capitanio U, Dehò F, Ali SM, Chung JH, Ross JS, Salonia A, Briganti A, Montorsi F. Updated Results of PURE-01 with Preliminary Activity of Neoadjuvant Pembrolizumab in Patients with Muscle-invasive Bladder Carcinoma with Variant Histologies. Eur Urol. 2019 Nov 7. link to original article PubMed
Induction chemoradiotherapy
Cisplatin & RT
Cisplatin & RT: Cisplatin & Radiation Therapy
Regimen variant #1, cisplatin 40 mg/m2 qwk x 3
Study | Dates of enrollment | Evidence |
---|---|---|
Zapatero et al. 2009 | 1990-2007 | Non-randomized |
Hagan et al. 2003 (RTOG 97-06) | 1998-2000 | Phase 1/2 |
Note: Dosing is per Figure 1 of Zapatero et al. 2009.
Eligibility criteria
- Zapatero et al. 2009: T2 to T4 N0 M0 disease
- RTOG 97-06: T2 to T4a N0 M0 disease without hydronephrosis
Chemotherapy
- Cisplatin (Platinol) 20 mg/m2 IV over 30 minutes once per day on days 1, 2, 8, 9, 15, 16, given first
Radiotherapy
- Concurrent radiation therapy twice per day on days 1 to 5, 8 to 12, 15, 16, consisting of 1.8 Gy fractions x 12 fractions to the bladder and regional lymph nodes; 6 hours later, a 1.6 Gy fraction x 12 fractions is given to the "bladder tumor plus wide margin." Radiation therapy given 5 days per week. Total induction dose to bladder tumor: 40.8 Gy; total induction dose to regional lymph nodes: 21.6 Gy.
16-day course
Subsequent treatment
- 3 weeks after finishing radiation and chemotherapy, patients underwent restaging TURBT
- RTOG 97-06, patients with complete regression (R0): Cisplatin & RT consolidation
- RTOG 97-06, nonresponders: Cystectomy
Regimen variant #2, cisplatin 70 mg/m2 q3wk x 2
Study | Dates of enrollment | Evidence |
---|---|---|
Tester et al. 1996 (RTOG 88-02) | 1988-1990 | Phase 2 |
Note: Patients were restaged 2 weeks after completion of radiation with examination under anesthesia, cystoscopy with tumor-site biopsy, urinary cytology, and computed tomographic scan of pelvis.
Preceding treatment
- MCV x 2
Chemotherapy
- Cisplatin (Platinol) 70 mg/m2 IV once per day on days 1 & 22
Radiotherapy
- Concurrent radiation therapy 1.8 Gy once per day on days 1 to 5, 8 to 12, 15 to 19, 22 to 26, 29, 30 (22 fractions; total dose: 39.6 Gy)
4.5-week course
Subsequent treatment
- RTOG 88-02, patients with CR: Cisplatin & RT consolidation
- RTOG 88-02, patients without CR: Immediate cystectomy
Regimen variant #3, cisplatin 100 mg/m2 q3wk x 2
Study | Dates of enrollment | Evidence |
---|---|---|
Shipley et al. 1988 | 1980-1985 | Non-randomized |
Shipley et al. 1998 (RTOG 89-03) | 1990-1993 | Non-randomized part of phase 3 RCT |
Note: In RTOG 89-03, the patient is restaged 4 weeks after completion of radiation with examination under anesthesia, cystoscopy with tumor-site biopsy, and urinary cytology.
Preceding treatment
- RTOG 89-03: MCV versus no neoadjuvant therapy
Chemotherapy
- Cisplatin (Platinol) 100 mg/m2 IV once per day on days 1 & 22
Radiotherapy
- Concurrent radiation therapy 1.8 Gy once per day on days 1 to 5, 8 to 12, 15 to 19, 22 to 26, 29, 30 (22 fractions; total dose: 39.6 Gy)
4.5-week course
Subsequent treatment
- RTOG 89-03, patients not in CR: Cystectomy
- RTOG 89-03, patients in CR: Cisplatin & RT consolidation
References
- Shipley WU, Prout GR Jr, Einstein AB, Coombs LJ, Wajsman Z, Soloway MS, Englander L, Barton BA, Hafermann MD. Treatment of invasive bladder cancer by cisplatin and radiation in patients unsuited for surgery. JAMA. 1987 Aug 21;258(7):931-5. link to original article PubMed
- RTOG 88-02: Tester W, Caplan R, Heaney J, Venner P, Whittington R, Byhardt R, True L, Shipley W. Neoadjuvant combined modality program with selective organ preservation for invasive bladder cancer: results of Radiation Therapy Oncology Group phase II trial 8802. J Clin Oncol. 1996 Jan;14(1):119-26. link to original article contains dosing details in manuscript 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. link to original article contains dosing details in manuscript 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. Epub 2009 Jul 27. link to original article link to PMC article 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. link to original article contains dosing details in manuscript link to PMC article PubMed
- RTOG 97-06: Hagan MP, Winter KA, Kaufman DS, Wajsman Z, Zietman AL, Heney NM, Toonkel LM, Jones CU, Roberts JD, Shipley WU. RTOG 97-06: initial report of a phase I-II trial of selective bladder conservation using TURBT, twice-daily accelerated irradiation sensitized with cisplatin, and adjuvant MCV combination chemotherapy. Int J Radiat Oncol Biol Phys. 2003 Nov 1;57(3):665-72. link to original article contains dosing details in manuscript 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. Epub 2009 Jul 27. link to original article link to PMC article 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. link to original article contains dosing details in manuscript link to PMC article PubMed
- Zapatero A, Martín de Vidales C, Arellano R, Bocardo G, Pérez M, Ríos P. Updated results of bladder-sparing trimodality approach for invasive bladder cancer. Urol Oncol. 2010 Jul-Aug;28(4):368-74. Epub 2009 Apr 11. link to original article contains dosing details in manuscript PubMed
- Update: Zapatero A, Martín de Vidales C, Arellano R, Ibañez Y, Bocardo G, Perez M, Rabadan M, García Vicente F, Cruz Conde JA, Olivier C. Long-term results of two prospective bladder-sparing trimodality approaches for invasive bladder cancer: neoadjuvant chemotherapy and concurrent radio-chemotherapy. Urology. 2012 Nov;80(5):1056-62. Epub 2012 Sep 19. link to original article contains dosing details in manuscript PubMed
- SunRISe-2: NCT04658862
- SWOG S1806: NCT03775265
Cisplatin & Fluorouracil (CF) & RT
Regimen variant #1, 90/2400/24
Study | Dates of enrollment | Evidence |
---|---|---|
Kaufman et al. 2000 (RTOG 95-06) | 1995-1997 | Phase 1/2 |
Eligibility criteria
- RTOG 95-06: Clinical T2 to T4a Nx M0 disease without hydronephrosis and CrCl 60 mL/min/1.73m2 or more
Chemotherapy
- Cisplatin (Platinol) 15 mg/m2 IV over 60 minutes once per day on days 1 to 3, 15 to 17 given second, before radiation
- Fluorouracil (5-FU) 400 mg/m2 IV once per day on days 1 to 3, 15 to 17 given first
Supportive therapy
- IV hydration at 500 mL/h (no total volume specified) prior to 5-FU
Radiotherapy
- Concurrent radiation therapy 3 Gy fractions twice per day on days 1, 3, 15, 17, with the first fraction of each day given 1 to 2 hours after completion of chemotherapy and at least 4 hours between fractions, x 8 fractions (total induction dose: 24 Gy), administered to the whole bladder, bladder tumor volume, and pelvic lymph nodes
17-day course
Dose and schedule modifications
- Patients with grade III hematologic toxicity, defined as platelets less than 50 x 109/L or ANC less than 1800/μL, had chemotherapy and radiation therapy held for at least one week, with therapy resuming when platelets were at least 100 x 109/L and ANC at least 1800/μL.
Subsequent treatment
- Treatment followed by repeat cystoscopy, biopsy, and urine cytology in week 7 or 8
- RTOG 95-06, patients with complete response: CF & RT consolidation in week 9
- RTOG 95-06, incomplete responders: recommended to undergo radical cystectomy
Regimen variant #2, 135/2400/40.3
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Mitin et al. 2013 (RTOG 02-33) | 2002-2008 | Randomized Phase 2 (E-switch-ic) | Cisplatin, Paclitaxel, RT | Not reported |
Coen et al. 2018 (RTOG 0712) | 2008-2014 | Randomized Phase 2 (C) | Gemcitabine & RT | Not reported1 |
1RTOG 0712 was not statistically powered to compare regimens.
Note: Treatment was followed by repeat cystoscopy and biopsy. In RTOG 02-33, patients underwent reevaluation for response on week 7.
Chemotherapy
- Cisplatin (Platinol) 15 mg/m2 IV once per day on days 1 to 3, 8 to 10, 15 to 17
- Fluorouracil (5-FU) 400 mg/m2 IV once per day on days 1 to 3, 15 to 17
Radiotherapy
- Concurrent radiation therapy, with twice per day RT, with at least 4 hours between radiation therapy sessions as follows:
- Days 1 to 5, 8 to 12, 15 to 17: 1.6 Gy fractions to the pelvis every morning
- Days 1 to 5: 1.5 Gy fractions to the bladder every evening
- Days 8 to 12, 15 to 17: 1.5 Gy fractions to the tumor every evening
- Total doses: pelvis: 20.8 Gy; whole bladder: 28.3 Gy; bladder tumor volume 40.3 Gy.
17-day course
Subsequent treatment
- RTOG 02-33, patients with less than stage T1 disease: CF & RT consolidation
- RTOG 02-33, patients with at least stage T1 disease: Radical cystectomy on week 9, then adjuvant PGC
- RTOG 0712, patients with complete response: CF & RT consolidation
- RTOG 0712, incomplete responders: Radical cystectomy
References
- RTOG 95-06: Kaufman DS, Winter KA, Shipley WU, Heney NM, Chetner MP, Souhami L, Zlotecki RA, Sause WT, True LD. The initial results in muscle-invading bladder cancer of RTOG 95-06: phase I/II trial of transurethral surgery plus radiation therapy with concurrent cisplatin and 5-fluorouracil followed by selective bladder preservation or cystectomy depending on the initial response. Oncologist. 2000;5(6):471-6. link to original article contains dosing details in manuscript 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. Epub 2009 Jul 27. link to original article link to PMC article 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. link to original article contains dosing details in manuscript link to PMC article PubMed
- RTOG 02-33: Mitin T, Hunt D, Shipley WU, Kaufman DS, Uzzo R, Wu CL, Buyyounouski MK, Sandler H, Zietman AL. Transurethral surgery and twice-daily radiation plus paclitaxel-cisplatin or fluorouracil-cisplatin with selective bladder preservation and adjuvant chemotherapy for patients with muscle invasive bladder cancer (RTOG 0233): a randomised multicentre phase 2 trial. Lancet Oncol. 2013 Aug;14(9):863-72. Epub 2013 Jul 1. link to original article contains dosing details in manuscript link to PMC article PubMed NCT00055601
- 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. Epub 2009 Jul 27. link to original article link to PMC article 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. link to original article contains dosing details in manuscript link to PMC article PubMed
- RTOG 0712: Coen JJ, Zhang P, Saylor PJ, Lee CT, Wu CL, Parker W, Lautenschlaeger T, Zietman AL, Efstathiou JA, Jani AB, Kucuk O, Souhami L, Rodgers JP, Sandler HM, Shipley WU. Bladder preservation with twice-a-day radiation plus fluorouracil/cisplatin or once daily radiation plus gemcitabine for muscle-invasive bladder cancer: NRG/RTOG 0712-a randomized phase II trial. J Clin Oncol. 2019 Jan 1;37(1):44-51. Epub 2018 Nov 15. link to original article contains dosing details in manuscript link to PMC article PubMed NCT00777491
Cisplatin, Paclitaxel, RT
Regimen variant #1, 40/50 x 3 + 40.3 Gy
Study | Dates of enrollment | Evidence |
---|---|---|
Kaufman et al. 2008 (RTOG 99-06) | NR in abstract | Phase 1/2 |
Note: the abstract of Kaufman et al. 2009 said that patients with "greater than Stage T1 disease" were recommended for cystectomy, but Figure 1 clarified that it was greater than or equal to ypT1 disease. On week 7, over 3 weeks after induction therapy, patients under reevaluation with exam under anesthesia, cystoscopy with tumor site biopsy, and urine cytology.
Preceding treatment
- TURBT, within 4 to 6 weeks
Chemotherapy
- Cisplatin (Platinol) 20 mg/m2 IV once per day on days 1, 2, 8, 9, 15, 16
- Paclitaxel (Taxol) 50 mg/m2 IV once per day on days 1, 8, 15
Radiotherapy
- Concurrent radiation therapy twice per day on days 1 to 5, 8 to 12, 15 to 17; 4 to 6 hours between radiation sessions. Kaufman et al. 2008 (RTOG 99-06) was unclear about exact radiation treatment plan, but it appears to have been the same as described in Mitin et al. 2013 (RTOG 02-33), which used:
- 1.6 Gy fractions to the pelvis every morning on days 1 to 5, 8 to 12, 15 to 17
- 1.5 Gy fractions to the bladder every evening on days 1 to 5
- 1.5 Gy fractions to the tumor every evening on days 8 to 12, 15 to 17
- Total doses: pelvis: 20.8 Gy; whole bladder: 28.3 Gy; bladder tumor volume 40.3 Gy.
3-week course
Subsequent treatment
- RTOG 02-33, patients with less than stage ypT1 disease: Cisplatin, paclitaxel, RT consolidation
- RTOG 02-33, patients with at least stage ypT1 disease: Radical cystectomy, then adjuvant GC
Regimen variant #2, 45/50 x 3 + 40.3 Gy
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Mitin et al. 2013 (RTOG 02-33) | 2002-2008 | Randomized Phase 2 (E-switch-ic) | Cisplatin, Fluorouracil, RT | Not reported |
Chemotherapy
- Cisplatin (Platinol) 15 mg/m2 IV once per day on days 1 to 3, 8 to 10, 15 to 17
- Paclitaxel (Taxol) 50 mg/m2 IV once per day on days 1, 8, 15
Radiotherapy
- Concurrent radiation therapy twice per day on days 1 to 5, 8 to 12, 15 to 17, with at least 4 hours between radiation therapy sessions:
- 1.6 Gy fractions to the pelvis every morning on days 1 to 5, 8 to 12, 15 to 17
- 1.5 Gy fractions to the bladder every evening on days 1 to 5
- 1.5 Gy fractions to the tumor every evening on days 8 to 12, 15 to 17
- Total doses: pelvis: 20.8 Gy; whole bladder: 28.3 Gy; bladder tumor volume 40.3 Gy.
3-week course
Subsequent treatment
- On week 7, patients under reevaluation for response
- RTOG 02-33, patients with less than stage ypT1 disease: Cisplatin, paclitaxel, RT consolidation
- RTOG 02-33, patients with at least stage ypT1 disease: Radical cystectomy on week 9, then adjuvant PGC
References
- RTOG 99-06: Kaufman DS, Winter KA, Shipley WU, Heney NM, Wallace HJ 3rd, Toonkel LM, Zietman AL, Tanguay S, Sandler HM. Phase I-II RTOG study (99-06) of patients with muscle-invasive bladder cancer undergoing transurethral surgery, paclitaxel, cisplatin, and twice-daily radiotherapy followed by selective bladder preservation or radical cystectomy and adjuvant chemotherapy. Urology. 2009 Apr;73(4):833-7. Epub 2008 Dec 18. link to original article contains dosing details in manuscript 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. Epub 2009 Jul 27. link to original article link to PMC article 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. link to original article contains dosing details in manuscript link to PMC article PubMed
- RTOG 02-33: Mitin T, Hunt D, Shipley WU, Kaufman DS, Uzzo R, Wu CL, Buyyounouski MK, Sandler H, Zietman AL. Transurethral surgery and twice-daily radiation plus paclitaxel-cisplatin or fluorouracil-cisplatin with selective bladder preservation and adjuvant chemotherapy for patients with muscle invasive bladder cancer (RTOG 0233): a randomised multicentre phase 2 trial. Lancet Oncol. 2013 Aug;14(9):863-72. Epub 2013 Jul 1. link to original article contains dosing details in manuscript link to PMC article PubMed NCT00055601
- 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. Epub 2009 Jul 27. link to original article link to PMC article 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. link to original article contains dosing details in manuscript link to PMC article PubMed
Fluorouracil, Mitomycin, RT
Fluorouracil, Mitomycin, RT: Fluorouracil, Mitomycin, Radiation Therapy
Regimen variant #1, 55 Gy
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
James et al. 2012 (BC2001) | 2001-2008 | Phase 3 (E-esc) | Radiation therapy | Might have superior DFS1 (secondary endpoint) (HR 0.78, 95% CI 0.60-1.02) |
1Reported efficacy is based on the 2022 update.
Chemotherapy
- Fluorouracil (5-FU) 500 mg/m2/day IV continuous infusion over 120 hours, started on days 1 & 16 (total dose: 5000 mg/m2)
- Mitomycin (Mutamycin) 12 mg/m2 IV bolus once on day 1
Radiotherapy
- Concurrent External beam radiotherapy 2.75 Gy once per day on days 1 to 5, 8 to 12, 15 to 19, 22 to 26 (20 fractions; total dose: 55 Gy)
4-week course
Regimen variant #2, 64 Gy
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
James et al. 2012 (BC2001) | 2001-2008 | Phase 3 (E-esc) | Radiation therapy | Might have superior DFS1 (secondary endpoint) (HR 0.78, 95% CI 0.60-1.02) |
1Reported efficacy is based on the 2022 update.
Chemotherapy
- Fluorouracil (5-FU) 500 mg/m2/day IV continuous infusion over 120 hours, started on days 1 & 16 (total dose: 5000 mg/m2)
- Mitomycin (Mutamycin) 12 mg/m2 IV bolus once on day 1
Radiotherapy
- Concurrent External beam radiotherapy 2 Gy per day on days 1 to 5, 8 to 12, 15 to 19, 22 to 26, 29 to 33, 36 to 40, 42, 43 (32 fractions; total dose: 64 Gy)
6.5-week course
References
- BC2001: James ND, Hussain SA, Hall E, Jenkins P, Tremlett J, Rawlings C, Crundwell M, Sizer B, Sreenivasan T, Hendron C, Lewis R, Waters R, Huddart RA; BC2001 Investigators. Radiotherapy with or without chemotherapy in muscle-invasive bladder cancer. N Engl J Med. 2012 Apr 19;366(16):1477-88. link to original article link to supplementary index contains dosing details in manuscript PubMed NCT00024349
- Update: Hall E, Hussain SA, Porta N, Lewis R, Crundwell M, Jenkins P, Rawlings C, Tremlett J, Sreenivasan T, Wallace J, Syndikus I, Sheehan D, Lydon A, Huddart R, James N; BC2001 Investigators. Chemoradiotherapy in Muscle-invasive Bladder Cancer: 10-yr Follow-up of the Phase 3 Randomised Controlled BC2001 Trial. Eur Urol. 2022 Sep;82(3):273-279. Epub 2022 May 14. link to original article PubMed
Gemcitabine & RT
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Coen et al. 2018 (RTOG 0712) | 2008-2014 | Randomized Phase 2 (E-de-esc) | CF & RT | Not reported1 |
1This trial was not statistically powered to compare regimens.
Note: Treatment was followed by repeat cystoscopy and biopsy.
Chemotherapy
- Gemcitabine (Gemzar) 27 mg/m2 IV once per day on days 1, 4, 8, 11, 15, 18, 22, 25
Radiotherapy
- Concurrent radiation therapy 2 Gy per day to the pelvis on days 1 to 10, then 2 Gy per day to the bladder on days 11 to 14, then 2 Gy per day to the bladder tumor on days 15 to 20
- Total doses: pelvis: 20 Gy; whole bladder: 28 Gy; bladder tumor volume 40 Gy
3-week course
Subsequent treatment
- RTOG 0712, patients with complete response: Gemcitabine & RT consolidation
- RTOG 0712, incomplete responders: Radical cystectomy
References
- RTOG 0712: Coen JJ, Zhang P, Saylor PJ, Lee CT, Wu CL, Parker W, Lautenschlaeger T, Zietman AL, Efstathiou JA, Jani AB, Kucuk O, Souhami L, Rodgers JP, Sandler HM, Shipley WU. Bladder preservation with twice-a-day radiation plus fluorouracil/cisplatin or once daily radiation plus gemcitabine for muscle-invasive bladder cancer: NRG/RTOG 0712-a randomized phase II trial. J Clin Oncol. 2019 Jan 1;37(1):44-51. Epub 2018 Nov 15. link to original article contains dosing details in manuscript link to PMC article PubMed NCT00777491
- SunRISe-2: NCT04658862
Paclitaxel & RT
Regimen variant #1, normo-fractionated RT
Study | Dates of enrollment | Evidence |
---|---|---|
Zapatero et al. 2012 | 1990-2010 | Non-randomized, fewer than 20 pts |
Note: Patients who had "mild renal insufficiency" received paclitaxel instead of cisplatin and had T2 to T4 N0 M0 disease.
Chemotherapy
- Paclitaxel (Taxol) 50 mg/m2 IV once per week, given 6 hours before radiation therapy
Radiotherapy
- Concurrent radiation therapy, total induction and consolidation dose of 64 to 66 Gy; Zapatero et al. 2012 did not specify how much of this dose was given during induction therapy vs. consolidation therapy.
One course
Subsequent treatment
- 3 weeks after finishing radiation and chemotherapy, patients underwent restaging TURBT
- Zapatero et al. 2012, patients with complete regression (R0): Paclitaxel & RT consolidation
- Zapatero et al. 2012, nonresponders: Cystectomy
Regimen variant #2, AHFRT
Study | Dates of enrollment | Evidence |
---|---|---|
Zapatero et al. 2012 | 1990-2010 | Non-randomized, fewer than 20 pts |
Note: Patients who had "mild renal insufficiency" received paclitaxel instead of cisplatin and had T2 to T4 N0 M0 disease.
Chemotherapy
- Paclitaxel (Taxol) 50 mg/m2 IV once per week, given 6 hours before radiation therapy
Radiotherapy
- Concurrent radiation therapy with twice per day radiation, consisting of 1.8 Gy fractions x 12 fractions to the bladder and regional lymph nodes; 6 hours later, a 1.6 Gy fraction x 12 fractions is given to the "bladder tumor plus wide margin." Total induction dose to bladder tumor: 40.8 Gy; total induction dose to regional lymph nodes: 21.6 Gy. Zapatero et al. 2012 did not specify the precise schedule of radiation therapy.
One course
Subsequent treatment
- 3 weeks after finishing radiation and chemotherapy, patients underwent restaging TURBT
- Zapatero et al. 2012, patients with complete regression (R0): Paclitaxel & RT consolidation
- Zapatero et al. 2012, nonresponders: Cystectomy
Regimen variant #3, 64.8 Gy
Study | Dates of enrollment | Evidence |
---|---|---|
Michaelson et al. 2016 (RTOG 0524) | 2005-2013 | Phase 1/2 |
Chemotherapy
- Paclitaxel (Taxol) 50 mg/m2 IV once per day on days 1, 8, 15, 22, 29, 36, 42
Radiotherapy
- Concurrent radiation therapy 1.80 Gy per day; 64.8 Gy total in 36 fractions
One course
References
- Zapatero A, Martín de Vidales C, Arellano R, Ibañez Y, Bocardo G, Perez M, Rabadan M, García Vicente F, Cruz Conde JA, Olivier C. Long-term results of two prospective bladder-sparing trimodality approaches for invasive bladder cancer: neoadjuvant chemotherapy and concurrent radio-chemotherapy. Urology. 2012 Nov;80(5):1056-62. Epub 2012 Sep 19. link to original article contains dosing details in manuscript PubMed
- RTOG 0524: Michaelson MD, Hu C, Pham HT, Dahl DM, Lee-Wu C, Swanson GP, Vuky J, Lee RJ, Souhami L, Chang B, George A, Sandler H, Shipley W. A Phase 1/2 Trial of a Combination of Paclitaxel and Trastuzumab With Daily Irradiation or Paclitaxel Alone With Daily Irradiation After Transurethral Surgery for Noncystectomy Candidates With Muscle-Invasive Bladder Cancer (Trial NRG Oncology RTOG 0524). Int J Radiat Oncol Biol Phys. 2017 Apr 1;97(5):995-1001. Epub 2016 Dec 19. link to original article link to PMC article PubMed
Radiation therapy
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Zapatero et al. 2000 | 1989-1997 | Non-randomized | ||
James et al. 2012 (BC2001) | 2001-2008 | Phase 3 (C) | Fluorouracil, Mitomycin, RT | Might have inferior DFS1 |
1Reported efficacy is based on the 2022 update.
Preceding treatment
- Zapatero et al. 2000, depending on response: MCV x 3 or cystectomy
Radiotherapy
- External beam radiotherapy by the following response-based criteria:
- CR: 2 Gy fractions given 5 days per week, with total bladder dose of 60 Gy. Total dose to regional lymph nodes: 50 Gy.
- Less than CR: total dose to the bladder of 64 to 66 Gy. No further details given about fractionation, schedule, or dose to lymph nodes.
References
- Zapatero A, Martín de Vidales C, Marín A, Cerezo L, Arellano R, Rabadán M, Pérez-Torrubia A. Invasive bladder cancer: a single-institution experience with bladder-sparing approach. Int J Cancer. 2000 Oct 20;90(5):287-94. link to original article contains dosing details in manuscript PubMed
- Update: Zapatero A, Martín de Vidales C, Arellano R, Bocardo G, Pérez M, Ríos P. Updated results of bladder-sparing trimodality approach for invasive bladder cancer. Urol Oncol. 2010 Jul-Aug;28(4):368-74. Epub 2009 Apr 11. link to original article contains dosing details in manuscript PubMed
- Update: Zapatero A, Martín de Vidales C, Arellano R, Ibañez Y, Bocardo G, Perez M, Rabadan M, García Vicente F, Cruz Conde JA, Olivier C. Long-term results of two prospective bladder-sparing trimodality approaches for invasive bladder cancer: neoadjuvant chemotherapy and concurrent radio-chemotherapy. Urology. 2012 Nov;80(5):1056-62. Epub 2012 Sep 19. link to original article PubMed
- BC2001: James ND, Hussain SA, Hall E, Jenkins P, Tremlett J, Rawlings C, Crundwell M, Sizer B, Sreenivasan T, Hendron C, Lewis R, Waters R, Huddart RA; BC2001 Investigators. Radiotherapy with or without chemotherapy in muscle-invasive bladder cancer. N Engl J Med. 2012 Apr 19;366(16):1477-88. link to original article contains dosing details in manuscript PubMed NCT00024349
- Update: Hall E, Hussain SA, Porta N, Lewis R, Crundwell M, Jenkins P, Rawlings C, Tremlett J, Sreenivasan T, Wallace J, Syndikus I, Sheehan D, Lydon A, Huddart R, James N; BC2001 Investigators. Chemoradiotherapy in Muscle-invasive Bladder Cancer: 10-yr Follow-up of the Phase 3 Randomised Controlled BC2001 Trial. Eur Urol. 2022 Sep;82(3):273-279. Epub 2022 May 14. link to original article PubMed
Consolidation chemoradiotherapy
Cisplatin & RT
Cisplatin & RT: Cisplatin & Radiation Therapy
Regimen variant #1, cisplatin 40 mg/m2/wk x 2, AHFRT
Study | Dates of enrollment | Evidence |
---|---|---|
Zapatero et al. 2000 | 1989-1997 | Non-randomized |
Hagan et al. 2003 (RTOG 97-06) | 1998-2000 | Phase 1/2 |
Note: Dosing is per Figure 1 of Zapatero et al. 2010.
Preceding treatment
- Zapatero et al. 2000, depending on response: Cisplatin & RT induction or cystectomy
Chemotherapy
- Cisplatin (Platinol) 20 mg/m2 IV over 30 minutes once per day on days 1, 2, 8, 9 given first
Radiotherapy
- Concurrent radiation therapy 1.5 Gy fractions twice per day on days 1 to 5, 8 to 12, 15, 16 (16 fractions; total consolidation dose: 24 Gy). After induction radiation therapy and consolidation radiation therapy, total dose to the bladder is 64.8 Gy; total dose to lymph nodes is 45.6 Gy.
Subsequent treatment
- RTOG 97-06: Adjuvant MCV
Regimen variant #2, cisplatin 70 mg/m2 x 1
Study | Dates of enrollment | Evidence |
---|---|---|
Tester et al. 1996 (RTOG 88-02) | 1988-1990 | Phase 2 |
Preceding treatment
- RTOG 88-02, depending on response, treatment preceded by: cisplatin & RT induction or cystectomy
Chemotherapy
- Cisplatin (Platinol) 70 mg/m2 IV once on day 1
Radiotherapy
- Concurrent radiation therapy 1.8 Gy fractions once per day on days 1 to 5, 8 to 12, 15 to 18 (14 fractions; total dose in consolidation phase: 25.2 Gy; total overall dose in induction and consolidation phases: 64.8 Gy)
3-week course
Regimen variant #3, cisplatin 100 mg/m2 x 1
Study | Dates of enrollment | Evidence |
---|---|---|
Shipley et al. 1998 (RTOG 89-03) | 1990-1993 | Non-randomized part of phase 3 RCT |
Preceding treatment
- RTOG 89-03, depending on response, treatment preceded by: cisplatin & RT induction or cystectomy
Chemotherapy
- Cisplatin (Platinol) 100 mg/m2 IV once on day 1
Radiotherapy
- Concurrent radiation therapy 1.8 Gy per day on days 1 to 5, 8 to 12, 15 to 18 (14 fractions; total dose in consolidation phase: 39.6 Gy; total overall dose in induction and consolidation phases: 64.8 Gy)
3-week course
References
- RTOG 88-02: Tester W, Caplan R, Heaney J, Venner P, Whittington R, Byhardt R, True L, Shipley W. Neoadjuvant combined modality program with selective organ preservation for invasive bladder cancer: results of Radiation Therapy Oncology Group phase II trial 8802. J Clin Oncol. 1996 Jan;14(1):119-26. link to original article contains dosing details in manuscript 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. link to original article contains dosing details in manuscript 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. Epub 2009 Jul 27. link to original article link to PMC article 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. link to original article contains dosing details in manuscript link to PMC article PubMed
- Zapatero A, Martín de Vidales C, Marín A, Cerezo L, Arellano R, Rabadán M, Pérez-Torrubia A. Invasive bladder cancer: a single-institution experience with bladder-sparing approach. Int J Cancer. 2000 Oct 20;90(5):287-94. link to original article PubMed
- Update: Zapatero A, Martín de Vidales C, Arellano R, Bocardo G, Pérez M, Ríos P. Updated results of bladder-sparing trimodality approach for invasive bladder cancer. Urol Oncol. 2010 Jul-Aug;28(4):368-74. Epub 2009 Apr 11. link to original article contains dosing details in manuscript PubMed
- Update: Zapatero A, Martín de Vidales C, Arellano R, Ibañez Y, Bocardo G, Perez M, Rabadan M, García Vicente F, Cruz Conde JA, Olivier C. Long-term results of two prospective bladder-sparing trimodality approaches for invasive bladder cancer: neoadjuvant chemotherapy and concurrent radio-chemotherapy. Urology. 2012 Nov;80(5):1056-62. Epub 2012 Sep 19. link to original article contains dosing details in manuscript PubMed
- RTOG 97-06: Hagan MP, Winter KA, Kaufman DS, Wajsman Z, Zietman AL, Heney NM, Toonkel LM, Jones CU, Roberts JD, Shipley WU. RTOG 97-06: initial report of a phase I-II trial of selective bladder conservation using TURBT, twice-daily accelerated irradiation sensitized with cisplatin, and adjuvant MCV combination chemotherapy. Int J Radiat Oncol Biol Phys. 2003 Nov 1;57(3):665-72. link to original article contains dosing details in manuscript 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. Epub 2009 Jul 27. link to original article link to PMC article 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. link to original article contains dosing details in manuscript link to PMC article PubMed
Cisplatin & Fluorouracil (CF) & RT
Regimen variant #1, 30/1200 x 2 + 64.3 Gy
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Mitin et al. 2013 (RTOG 02-33) | 2002-2008 | Randomized Phase 2 (E-switch-ic) | Cisplatin, Paclitaxel, RT | Not reported |
Note: Consolidation starts starts on week 8.
Preceding treatment
- Cisplatin, 5-FU, RT induction
Chemotherapy
Starts on week 8.
- Cisplatin (Platinol) 15 mg/m2 IV once per day on days 1, 2, 8, 9
- Fluorouracil (5-FU) 400 mg/m2 IV once per day on days 1 to 3, 8 to 10
Radiotherapy
- Concurrent radiation therapy 1.5 Gy twice per day on days 1 to 5, 8 to 10 (16 fractions, given twice per day x 8 days). Total dose during consolidation is 24 Gy. Total dose after induction therapy and consolidation therapy: pelvis: 44.8 Gy; whole bladder: 52.3 Gy; bladder tumor volume 64.3 Gy.
2-week course
Subsequent treatment
- Adjuvant PGC
Regimen variant #2, 45/1200 x 2 + 44 Gy
Study | Dates of enrollment | Evidence |
---|---|---|
Kaufman et al. 2000 (RTOG 95-06) | 1995-1997 | Phase 1/2 |
Treatment starts on week 9.
Preceding treatment
- RTOG 95-06, depending on response, treatment preceded by: cisplatin, fluorouracil, RT induction or cystectomy
Chemotherapy
- Cisplatin (Platinol) 15 mg/m2 IV over 60 minutes once per day on days 1 to 3, 15 to 17, given second
- Fluorouracil (5-FU) 400 mg/m2 IV once per day on days 1 to 3, 15 to 17, given first
Radiotherapy
- Concurrent radiation therapy 2.5 Gy fractions twice per day on days 1, 3, 15, 17, with at least 4 hours between fractions, x 8 fractions (total consolidation dose: 20 Gy), administered to the whole bladder and bladder tumor volume. The total dose to the whole bladder and bladder tumor volume was 44 Gy in 16 fractions; the total dose to the pelvic lymph nodes was 24 Gy in 8 fractions.
Supportive therapy
- IV hydration at 500 mL/h (no total volume specified) prior to 5-FU
17-day course
Dose and schedule modifications
- Patients with grade III hematologic toxicity, defined as platelets less than 50 x 109/L or ANC less than 1800/μL, had chemotherapy and radiation therapy held for at least one week, with therapy resuming when platelets were at least 100 x 109/L and ANC at least 1800/μL.
References
- RTOG 95-06: Kaufman DS, Winter KA, Shipley WU, Heney NM, Chetner MP, Souhami L, Zlotecki RA, Sause WT, True LD. The initial results in muscle-invading bladder cancer of RTOG 95-06: phase I/II trial of transurethral surgery plus radiation therapy with concurrent cisplatin and 5-fluorouracil followed by selective bladder preservation or cystectomy depending on the initial response. Oncologist. 2000;5(6):471-6. link to original article contains dosing details in manuscript 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. Epub 2009 Jul 27. link to original article link to PMC article 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. link to original article contains dosing details in manuscript link to PMC article PubMed
- RTOG 02-33: Mitin T, Hunt D, Shipley WU, Kaufman DS, Uzzo R, Wu CL, Buyyounouski MK, Sandler H, Zietman AL. Transurethral surgery and twice-daily radiation plus paclitaxel-cisplatin or fluorouracil-cisplatin with selective bladder preservation and adjuvant chemotherapy for patients with muscle invasive bladder cancer (RTOG 0233): a randomised multicentre phase 2 trial. Lancet Oncol. 2013 Aug;14(9):863-72. Epub 2013 Jul 1. link to original article contains dosing details in manuscript link to PMC article PubMed NCT00055601
- 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. Epub 2009 Jul 27. link to original article link to PMC article 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. link to original article contains dosing details in manuscript link to PMC article PubMed
Cisplatin, Paclitaxel, RT
Regimen variant #1, 30/50 x 2 + 64.3 Gy
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Mitin et al. 2013 (RTOG 02-33) | 2002-2008 | Randomized Phase 2 (E-switch-ic) | Cisplatin, 5-FU, RT | Not reported |
Note: Consolidation starts starts on week 8.
Preceding treatment
- Cisplatin, Paclitaxel, RT induction
Chemotherapy
- Cisplatin (Platinol) 15 mg/m2 IV once per day on days 1, 2, 8, 9
- Paclitaxel (Taxol) 50 mg/m2 IV once per day on days 1 & 8
Radiotherapy
- Concurrent radiation therapy 1.5 Gy twice per day on days 1 to 5, 8 to 10 (16 fractions, given twice per day x 8 days). Total dose during consolidation is 24 Gy. Total dose after induction therapy and consolidation therapy: pelvis: 44.8 Gy; whole bladder: 52.3 Gy; bladder tumor volume 64.3 Gy.
2-week course
Subsequent treatment
- Adjuvant PGC
Regimen variant #2, 40/50 x 2 + 64.3 Gy
Study | Dates of enrollment | Evidence |
---|---|---|
Kaufman et al. 2008 (RTOG 99-06) | NR in abstract | Phase 1/2 |
Consolidation starts starts on week 8.
Preceding treatment
- Cisplatin, Paclitaxel, RT induction
Chemotherapy
- Cisplatin (Platinol) 20 mg/m2 IV once per day on days 1, 2, 8, 9
- Paclitaxel (Taxol) 50 mg/m2 IV once per day on days 1 & 8
7-day cycle for 2 cycles
Radiotherapy
- Concurrent radiation therapy 1.5 Gy twice per day on days 1 to 5, 8 to 10 (16 fractions, given twice per day at a 4 to 6 hour interval between treatments). Total dose during consolidation is 24 Gy. Total dose after induction therapy and consolidation therapy: pelvis: 44.8 Gy; whole bladder: 52.3 Gy; bladder tumor volume 64.3 Gy.
2-week course
Subsequent treatment
- Adjuvant GC
References
- RTOG 99-06: Kaufman DS, Winter KA, Shipley WU, Heney NM, Wallace HJ 3rd, Toonkel LM, Zietman AL, Tanguay S, Sandler HM. Phase I-II RTOG study (99-06) of patients with muscle-invasive bladder cancer undergoing transurethral surgery, paclitaxel, cisplatin, and twice-daily radiotherapy followed by selective bladder preservation or radical cystectomy and adjuvant chemotherapy. Urology. 2009 Apr;73(4):833-7. Epub 2008 Dec 18. link to original article contains dosing details in manuscript 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. Epub 2009 Jul 27. link to original article link to PMC article 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. link to original article contains dosing details in manuscript link to PMC article PubMed
- RTOG 02-33: Mitin T, Hunt D, Shipley WU, Kaufman DS, Uzzo R, Wu CL, Buyyounouski MK, Sandler H, Zietman AL. Transurethral surgery and twice-daily radiation plus paclitaxel-cisplatin or fluorouracil-cisplatin with selective bladder preservation and adjuvant chemotherapy for patients with muscle invasive bladder cancer (RTOG 0233): a randomised multicentre phase 2 trial. Lancet Oncol. 2013 Aug;14(9):863-72. Epub 2013 Jul 1. link to original article contains dosing details in manuscript link to PMC article PubMed NCT00055601
- 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. Epub 2009 Jul 27. link to original article link to PMC article 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. link to original article contains dosing details in manuscript link to PMC article PubMed
Paclitaxel & RT
Regimen variant #1, normo-fractionated RT
Study | Dates of enrollment | Evidence |
---|---|---|
Zapatero et al. 2012 | 1990-2010 | Non-randomized, fewer than 20 pts |
Preceding treatment
- Zapatero et al. 2012, depending on response, treatment preceded by: paclitaxel & RT induction or cystectomy
Chemotherapy
- Paclitaxel (Taxol) 50 mg/m2 IV once per week, given 6 hours before radiation therapy
Radiotherapy
- Concurrent radiation therapy, total induction and consolidation dose of 64 to 66 Gy; Zapatero et al. 2012 did not specify how much of this dose was given during induction therapy vs. consolidation therapy.
One course
Regimen variant #2, AHFRT
Study | Dates of enrollment | Evidence |
---|---|---|
Zapatero et al. 2012 | 1990-2010 | Non-randomized, fewer than 20 pts |
Preceding treatment
- Zapatero et al. 2012, depending on response, treatment preceded by: paclitaxel & RT induction or cystectomy
Chemotherapy
- Paclitaxel (Taxol) 50 mg/m2 IV once per day on days 1 & 8, given 6 hours before radiation therapy
Radiotherapy
- Concurrent radiation therapy 1.5 Gy twice per day on days 1 to 5, 8 to 10 (16 fractions; total consolidation dose: 24 Gy). After induction radiation therapy and consolidation radiation therapy, total dose to the bladder is 64.8 Gy; total dose to lymph nodes is 45.6 Gy.
One course
References
- Zapatero A, Martín de Vidales C, Arellano R, Ibañez Y, Bocardo G, Perez M, Rabadan M, García Vicente F, Cruz Conde JA, Olivier C. Long-term results of two prospective bladder-sparing trimodality approaches for invasive bladder cancer: neoadjuvant chemotherapy and concurrent radio-chemotherapy. Urology. 2012 Nov;80(5):1056-62. Epub 2012 Sep 19. link to original article contains dosing details in manuscript PubMed
Adjuvant therapy
Cisplatin & Gemcitabine (GC)
Regimen
Study | Dates of enrollment | Evidence |
---|---|---|
Kaufman et al. 2008 (RTOG 99-06) | NR in abstract | Phase 1/2 |
Preceding treatment
- RTOG 99-06, depending on response to induction, treatment starts: 12 weeks after cisplatin, paclitaxel, RT consolidation or 8 weeks after cystectomy
Chemotherapy
- Cisplatin (Platinol) 70 mg/m2 IV once on day 1
- Gemcitabine (Gemzar) 1000 mg/m2 IV once per day on days 1, 8, 15
28-day cycle for 4 cycles
References
- RTOG 99-06: Kaufman DS, Winter KA, Shipley WU, Heney NM, Wallace HJ 3rd, Toonkel LM, Zietman AL, Tanguay S, Sandler HM. Phase I-II RTOG study (99-06) of patients with muscle-invasive bladder cancer undergoing transurethral surgery, paclitaxel, cisplatin, and twice-daily radiotherapy followed by selective bladder preservation or radical cystectomy and adjuvant chemotherapy. Urology. 2009 Apr;73(4):833-7. Epub 2008 Dec 18. link to original article contains dosing details in manuscript 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. Epub 2009 Jul 27. link to original article link to PMC article 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. link to original article contains dosing details in manuscript link to PMC article PubMed
Cisplatin & Methotrexate
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy | Comparative Toxicity |
---|---|---|---|---|---|
Lehmann et al. 2005 (AUO-AB 05/95) | 1994-2000 | Phase 3 (E-de-esc) | M-VEC x 3 | Inconclusive whether non-inferior PFS (primary endpoint) | Less toxic |
Preceding treatment
Chemotherapy
References
- AUO-AB 05/95: Lehmann J, Retz M, Wiemers C, Beck J, Thüroff J, Weining C, Albers P, Frohneberg D, Becker T, Funke PJ, Walz P, Langbein S, Reiher F, Schiller M, Miller K, Roth S, Kälble T, Sternberg D, Wellek S, Stöckle M; AUO. Adjuvant cisplatin plus methotrexate versus methotrexate, vinblastine, epirubicin, and cisplatin in locally advanced bladder cancer: results of a randomized, multicenter, phase III trial (AUO-AB 05/95). J Clin Oncol. 2005 Aug 1;23(22):4963-74. Epub 2005 Jun 6. link to original article PubMed
MCV
MCV: Methotrexate, Cisplatin, Vinblastine
Regimen
Study | Dates of enrollment | Evidence |
---|---|---|
Hagan et al. 2003 (RTOG 97-06) | 1998-2000 | Phase 1/2 |
Begins 8 weeks after consolidation. Note that only 45% of patients in RTOG 97-06 were able to complete all 3 cycles of MCV.
Preceding treatment
- Cisplatin & RT consolidation
Chemotherapy
- Methotrexate (MTX) 30 mg/m2 IV once per day on days 1, 15, 22
- Cisplatin (Platinol) 25 mg/m2 IV once per day on days 2 to 4
- Vinblastine (Velban) 3 mg/m2 IV once per day on days 2, 15, 22
28-day cycle for 3 cycles
References
- RTOG 97-06: Hagan MP, Winter KA, Kaufman DS, Wajsman Z, Zietman AL, Heney NM, Toonkel LM, Jones CU, Roberts JD, Shipley WU. RTOG 97-06: initial report of a phase I-II trial of selective bladder conservation using TURBT, twice-daily accelerated irradiation sensitized with cisplatin, and adjuvant MCV combination chemotherapy. Int J Radiat Oncol Biol Phys. 2003 Nov 1;57(3):665-72. link to original article contains dosing details in manuscript 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. Epub 2009 Jul 27. link to original article link to PMC article 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. link to original article contains dosing details in manuscript link to PMC article PubMed
PGC
PGC: Paclitaxel, Gemcitabine, Cisplatin
PCG: Paclitaxel, Cisplatin, Gemcitabine
Regimen variant #1, 100/2000/70
Study | Dates of enrollment | Evidence |
---|---|---|
Mitin et al. 2013 (RTOG 02-33) | 2002-2008 | Non-randomized part of phase 2 RCT |
Preceding treatment
- RTOG 02-33, depending on response, adjuvant chemotherapy began: 12 weeks after cisplatin, paclitaxel, RT versus cisplatin, 5-FU, RT or 8 weeks after cystectomy
Chemotherapy
- Paclitaxel (Taxol) 50 mg/m2 IV once per day on days 1 & 8
- Gemcitabine (Gemzar) 1000 mg/m2 IV once per day on days 1 & 8
- Cisplatin (Platinol) 35 mg/m2 IV once per day on days 1 & 8
21-day cycle for 4 cycles
Regimen variant #2, 160/2000/70
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Paz-Ares et al 2010 (SOGUG 99/01) | 2000-2007 | Phase 3 (E-esc) | Observation | Superior OS (primary endpoint) OS60: 60% vs 31% |
Note: This study prematurely closed due to poor recruitment and lacked adequate power to make firm conclusions, and has never been published in manuscript format to our knowledge.
Eligibility criteria
- SOGUG 99/01: pT3-4 and/or pN positive disease with adequate renal function (CrCl more than 50 mL/min/1.73m2)
Preceding treatment
- Cystectomy; the median time treatment started post-cystectomy was 48 days
Chemotherapy
- Paclitaxel (Taxol) 80 mg/m2 IV once per day on days 1 & 8
- Gemcitabine (Gemzar) 1000 mg/m2 IV once per day on days 1 & 8
- Cisplatin (Platinol) 70 mg/m2 IV once on day 1
21-day cycle for 4 cycles
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. link to abstract contains dosing details in manuscript
- RTOG 02-33: Mitin T, Hunt D, Shipley WU, Kaufman DS, Uzzo R, Wu CL, Buyyounouski MK, Sandler H, Zietman AL. Transurethral surgery and twice-daily radiation plus paclitaxel-cisplatin or fluorouracil-cisplatin with selective bladder preservation and adjuvant chemotherapy for patients with muscle invasive bladder cancer (RTOG 0233): a randomised multicentre phase 2 trial. Lancet Oncol. 2013 Aug;14(9):863-72. Epub 2013 Jul 1. link to original article contains dosing details in manuscript link to PMC article PubMed NCT00055601
- 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. Epub 2009 Jul 27. link to original article link to PMC article 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. link to original article contains dosing details in manuscript link to PMC article PubMed
Links
- EORTC Risk Tables for Predicting Recurrence and Progression in Individual Patients with Stage Ta T1 Bladder Cancer - predicts probability of recurrence and progression in 1 to 5 years
Urine assays
These are assays intended/being investigated as adjuncts to urine cytology and cystoscopy.
- Cxbladder (uRNA-2), a "urine based bladder cancer test (uRNA-2) which detects RNA markers in urine."
- ImmunoCyt™/uCyt+™, a cell-based detection assay which "uses fluorescent-labeled antibodies to 3 markers that are commonly found on malignant exfoliated urothelial cells."[1]
- UroVysion (Abbott Molecular) "designed to detect aneuploidy for chromosomes 3, 7, 17, and loss of the 9p21 locus via fluorescence in situ hybridization (FISH) in urine specimens from persons with hematuria suspected of having bladder cancer."
References
- ↑ Greene KL, Berry A, Konety BR. Diagnostic Utility of the ImmunoCyt/uCyt+ Test in Bladder Cancer. Rev Urol. 2006 Fall;8(4):190-7. link to PMC article PubMed