Revision as of 14:32, 27 November 2016

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31 regimens on this page 47 variants on this page

Intravesical chemotherapy

Bacillus Calmette-Guerin (BCG)

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Regimen #1, intravesical & percutaneous, with maintenance therapy

Study	Evidence	Comparator	Efficacy
Lamm et al. 2000	Phase III	Intravesical & percutaneous BCG, without maintenance therapy	Superior RFS

Induction therapy

Bacillus Calmette-Guerin (BCG) (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

Maintenance therapy

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-Guerin (BCG) (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 #2, intravesical & percutaneous, without maintenance therapy

Study	Evidence	Comparator	Efficacy
Lamm et al. 2000	Phase III	Intravesical & percutaneous BCG, with maintenance therapy	Inferior RFS

Immunotherapy

Bacillus Calmette-Guerin (BCG) (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 #3, low-dose BCG

Study	Evidence	Comparator	Efficacy
Ojea et al. 2007 (CUETO study 95011)	Phase III	Mitomycin	Superior DFS
Ojea et al. 2007 (CUETO study 95011)	Phase III	Very-low-dose BCG	Seems not superior

Treatment begins 14 to 21 days after transurethral resection of bladder cancer.

Induction therapy

Bacillus Calmette-Guerin (BCG) (Connaught strain) 27 mg intravesicularly once per day on days 1, 8, 15, 22, 29, 36

6-week course, then proceed to additional therapy

Additional therapy

Bacillus Calmette-Guerin (BCG) (Connaught strain) 27 mg intravesicularly once every 2 weeks

12-week course; 6 doses given during this course (i.e. once on weeks 1, 3, 5, 7, 9, 11)

References

Martínez-Piñeiro JA, Jiménez León J, Martínez-Piñeiro L Jr, Fiter L, Mosteiro JA, Navarro J, García Matres MJ, Cárcamo P. Bacillus Calmette-Guerin versus doxorubicin versus thiotepa: a randomized prospective study in 202 patients with superficial bladder cancer. J Urol. 1990 Mar;143(3):502-6. PubMed
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-Guerin 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 verified protocol PubMed
Sylvester RJ, van der MEIJDEN AP, Lamm DL. Intravesical bacillus Calmette-Guerin 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
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 Group (Club Urológico Español De Tratamiento Oncológico). A multicentre, randomised prospective trial comparing three intravesical adjuvant therapies for intermediate-risk superficial bladder cancer: low-dose bacillus Calmette-Guerin (27 mg) versus very low-dose bacillus Calmette-Guerin (13.5 mg) versus mitomycin C. Eur Urol. 2007 Nov;52(5):1398-406. Epub 2007 Apr 27. link to SD article contains verified protocol PubMed

Doxorubicin (Adriamycin)

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Regimen

Study	Evidence	Comparator	Efficacy
Martínez-Piñeiro et al. 1990	Phase III	BCG	Inferior RFS
Martínez-Piñeiro et al. 1990	Phase III	Thiotepa	Not reported

Inferior to BCG, included for reference purposes only.

Chemotherapy

Doxorubicin (Adriamycin) 50 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-Guerin versus doxorubicin versus thiotepa: a randomized prospective study in 202 patients with superficial bladder cancer. J Urol. 1990 Mar;143(3):502-6. PubMed

Mitomycin (Mutamycin)

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Regimen

Study	Evidence	Comparator	Efficacy
Ojea et al. 2007 (CUETO study 95011)	Phase III	Low-dose BCG	Inferior DFS
Ojea et al. 2007 (CUETO study 95011)	Phase III	Very-low-dose BCG	Seems not superior

Treatment begins 14 to 21 days after transurethral resection of bladder cancer.

Induction therapy

Mitomycin (Mutamycin) 30 mg intravesicularly once per day on days 1, 8, 15, 22, 29, 36

6-week course, then proceed to additional therapy

Additional therapy

Mitomycin (Mutamycin) 30 mg intravesicularly once every 2 weeks

12-week course; 6 doses given during this course (i.e. once on weeks 1, 3, 5, 7, 9, 11)

References

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 Group (Club Urológico Español De Tratamiento Oncológico). A multicentre, randomised prospective trial comparing three intravesical adjuvant therapies for intermediate-risk superficial bladder cancer: low-dose bacillus Calmette-Guerin (27 mg) versus very low-dose bacillus Calmette-Guerin (13.5 mg) versus mitomycin C. Eur Urol. 2007 Nov;52(5):1398-406. Epub 2007 Apr 27. link to SD article contains verified protocol PubMed

Pirarubicin (THP)

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Regimen

Study	Evidence	Comparator	Efficacy
Ito et al. 2013 (THP Monotherapy Study Group Trial)	Phase III	Observation	Seems to have superior RFS

Pirarubicin was given within 48 hours after nephroureterectomy.

Chemotherapy

Pirarubicin (THP) 30 mg in 30 mL normal saline intravesicularly, delivered through a catheter into the bladder, and retained for 30 minutes

1 dose

References

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 contains verified protocol PubMed

Placebo or observation

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Regimen

Study	Evidence	Comparator	Efficacy
Ito et al. 2013	Phase III	Pirarubicin	Seems to have inferior RFS

No active antineoplastic treatment; used as a comparator arm and included for reference purposes only.

References

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 contains verified protocol PubMed

Thiotepa (Thioplex)

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Regimen

Study	Evidence	Comparator	Efficacy
Martínez-Piñeiro et al. 1990	Phase III	BCG	Inferior RFS
Martínez-Piñeiro et al. 1990	Phase III	Doxorubicin	Not reported

Inferior to BCG, included for reference purposes only.

Chemotherapy

Thiotepa (Thioplex) 50 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-Guerin versus doxorubicin versus thiotepa: a randomized prospective study in 202 patients with superficial bladder cancer. J Urol. 1990 Mar;143(3):502-6. PubMed

Neoadjuvant chemotherapy

Cisplatin & Gemcitabine (GC)

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GC: Gemcitabine, Cisplatin

Regimen #1, single-dose cisplatin

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

Regimen #2, split-dose cisplatin

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

References

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 verified protocol PubMed

CMV; MCV

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CMV: Cisplatin, Methotrexate, Vinblastine
MCV: Methotrexate, Cisplatin, Vinblastine

Regimen

Study	Evidence	Comparator	Efficacy
International Collaboration of Trialists et al. 1999 (BA06 30894)	Phase III	No neoadjuvant therapy	Seems to have superior OS

Chemotherapy

Cisplatin (Platinol) 100 mg/m² IV once on day 2, before hydration
Methotrexate (MTX) 30 mg/m² IV bolus once per day on days 1 & 8
Vinblastine (Velban) 4 mg/m² IV bolus once per day on days 1 & 8

Supportive medications

Folinic acid (Leucovorin) 15 mg PO/IV every 6 hours for 4 doses (total daily dose: 60 mg/m²) on days 2 & 9; given after hydration, with the first dose 24 hours after the previous day's dose of methotrexate

21-day cycle for 3 cycles

References

Neoadjuvant cisplatin, methotrexate, and vinblastine chemotherapy for muscle-invasive bladder cancer: a randomised controlled trial. International collaboration of trialists. Lancet. 1999 Aug 14;354(9178):533-40. Erratum in: Lancet 1999 Nov 6;354(9190):1650. link to original article PubMed
1. Update: International Collaboration of Trialists; Medical Research Council Advanced Bladder Cancer Working Party (now the National Cancer Research Institute Bladder Cancer Clinical Studies Group); European Organisation for Research and Treatment of Cancer Genito-Urinary Tract Cancer Group; Australian Bladder Cancer Study Group; National Cancer Institute of Canada Clinical Trials Group; Finnbladder; Norwegian Bladder Cancer Study Group; Club Urologico Espanol de Tratamiento Oncologico Group, Griffiths G, Hall R, Sylvester R, Raghavan D, Parmar MK. 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 verified protocol PubMed

MVAC

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MVAC: Methotrexate, Vinblastine, Adriamycin (Doxorubicin), Cisplatin

Regimen

Study	Evidence	Comparator	Efficacy
Grossman et al. 2003 (SWOG S8710)	Phase III	No neoadjuvant therapy	Might have superior OS

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

References

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 verified protocol PubMed
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

MVAC (dose-dense/accelerated)

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ddMVAC: dose-dense Methotrexate, Vinblastine, Adriamycin (Doxorubicin), Cisplatin
AMVAC: Accelerated Methotrexate, Vinblastine, Adriamycin (Doxorubicin), Cisplatin

Regimen #1, dose-dense MVAC

Study	Evidence
Choueiri et al. 2014	Phase II

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 in 1 liter normal saline once on day 2

Supportive medications

Pegfilgrastim (Neulasta) 6 mg SC once on day 3 (approximately 24 hours after day 2 chemotherapy)

14-day cycle for 4 cycles

Cystectomy to be performed 4 to 10 weeks after completion of chemotherapy.

Regimen #2, accelerated MVAC

Study	Evidence
Plimack et al. 2014	Phase II

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 in 1 liter normal saline once on day 2
- Split dose cisplatin could be used at physician discretion for patients with creatinine clearance <60 mL/min: Cisplatin 35 mg/m2 IV once per day on days 1 & 2

Supportive medications

Pegfilgrastim (Neulasta) 6 mg SC once 24 to 48 hours after completion of chemotherapy
Antiemetics used often included Aprepitant (Emend), Ondansetron (Zofran), and Dexamethasone (Decadron) but were not specified by the trial.

14-day cycle for 3 cycles

Radical cystectomy with bilateral lymphadenectomy to be done within 4 to 8 weeks after the last cycle of chemotherapy.

References

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 verified protocol PubMed
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 verified protocol PubMed

No neoadjuvant therapy

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Regimen

Study	Evidence	Comparator	Efficacy
International Collaboration of Trialists et al. 1999 (BA06 30894)	Phase III	CMV	Seems to have inferior OS
Grossman et al. 2003 (SWOG S8710)	Phase III	MVAC	Might have inferior OS

No preoperative treatment; used as a comparator arm and here for reference purposes only.

References

Neoadjuvant cisplatin, methotrexate, and vinblastine chemotherapy for muscle-invasive bladder cancer: a randomised controlled trial. International collaboration of trialists. Lancet. 1999 Aug 14;354(9178):533-40. Erratum in: Lancet 1999 Nov 6;354(9190):1650. link to original article PubMed
1. Update: International Collaboration of Trialists; Medical Research Council Advanced Bladder Cancer Working Party (now the National Cancer Research Institute Bladder Cancer Clinical Studies Group); European Organisation for Research and Treatment of Cancer Genito-Urinary Tract Cancer Group; Australian Bladder Cancer Study Group; National Cancer Institute of Canada Clinical Trials Group; Finnbladder; Norwegian Bladder Cancer Study Group; Club Urologico Espanol de Tratamiento Oncologico Group, Griffiths G, Hall R, Sylvester R, Raghavan D, Parmar MK. 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 verified protocol PubMed
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 verified protocol PubMed
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

Neoadjuvant chemotherapy -> RT

MCV -> RT

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Regimen

Study	Evidence
Zapatero et al. 2000	Non-randomized

Patients had T2 to T4 Nx M0 disease.

Chemotherapy portion

Methotrexate (MTX) 30 mg/m² IV once per day on days 1 & 8
Vinblastine (Velban) 4 mg/m² IV once per day on days 1 & 8
Cisplatin (Platinol) 100 mg/m² IV once on day 1

21-day cycle for 3 cycles; after 3 cycles of chemotherapy, patients underwent cystoscopy, biopsy, and abdominal CT. Patients with complete response or who were not surgical candidates proceeded to radiation therapy which begins 4 to 6 weeks after completion of chemotherapy. Otherwise, patients proceeded to cystectomy.

Radiation therapy portion

Radiation therapy starts 4 to 6 weeks after completion of chemotherapy.

Patients who had complete response received radiation therapy, 2 Gy fractions given 5 days per week, with total bladder dose of 60 Gy. Total dose to regional lymph nodes: 50 Gy.
- Patients who did not have complete response received radiation therapy for a 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 verified protocol PubMed
1. Update: Zapatero A, Martin 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 verified protocol PubMed
2. Update: Zapatero A, Martin 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

Neoadjuvant chemotherapy -> concurrent chemotherapy & radiation therapy

MCV -> Cisplatin & RT

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MCV: Methotrexate, Cisplatin, Vinblastine
RT: Radiation Therapy

Regimen #1

Study	Evidence	Comparator	Efficacy
Shipley et al. 1998 (RTOG 89-03)	Phase III	Cisplatin & RT	Seems not superior

Neoadjuvant chemotherapy

Methotrexate (MTX) 30 mg/m² IV once per day on days 0, 14, 21
Vinblastine (Velban) 3 mg/m² IV once per day on days 1, 14, 21
Cisplatin (Platinol) 70 mg/m² IV once on day 1

28-day cycle for 2 cycles, followed by:

Neoadjuvant chemoradiotherapy

Cisplatin (Platinol) 100 mg/m² IV once per day on days 1 & 22
Concurrent radiation therapy, 1.8 Gy fractions x 22 fractions, given 5 times per week (total dose: 39.6 Gy)

1 treatment course; patient is restaged 4 weeks after completion of radiation with "examination under anesthesia, cystoscopy with tumor-site biopsy, and urinary cytology." Patients not in complete remission usually proceeded to cystectomy. Patients in compete remission usually proceeded to consolidation therapy.

Consolidation therapy

Cisplatin (Platinol) 100 mg/m² IV once on day 1
Concurrent radiation therapy, 1.8 Gy fractions x 14 fractions, given 5 times per week (total dose in consolidation phase: 25.2 Gy; total overall dose in induction and consolidation phases: 64.8 Gy)

3-week course

Regimen #2

Study	Evidence
Tester et al. 1996 (RTOG 88-02)	Phase II

Neoadjuvant 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, then patients proceeded to concurrent chemotherapy & radiation therapy

Induction therapy

Cisplatin (Platinol) 70 mg/m² IV once per day on days 1 & 22
Concurrent radiation therapy, 1.8 Gy fractions x 22 fractions (total dose: 39.6 Gy)

1 treatment course; patient is restaged 2 weeks after completion of radiation with "examination under anesthesia, cystoscopy with tumor-site biopsy, urinary cytology, and computed tomographic scan of pelvis." Patients with complete response--no evidence of disease on this evaluation--proceeded to consolidation radiotherapy. Patients without complete response proceeded immediately to cystectomy.

Consolidation therapy

Cisplatin (Platinol) 70 mg/m² IV once on day 1
Concurrent radiation therapy, 1.8 Gy fractions x 14 fractions (total dose in consolidation phase: 25.2 Gy; total overall dose in induction and consolidation phases: 64.8 Gy)

3-week course

References

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 verified protocol PubMed
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 verified protocol 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 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 Nov 3. link to original article contains verified protocol PubMed

Concurrent chemotherapy & radiation

Cisplatin & RT

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RT: Radiation Therapy

Regimen #1

Study	Evidence	Comparator	Efficacy
Shipley et al. 1998 (RTOG 89-03)	Phase III	MCV -> Cisplatin & RT	Seems not superior

Induction chemoradiotherapy

Cisplatin (Platinol) 100 mg/m² IV once per day on days 1 & 22
Concurrent radiation therapy, 1.8 Gy fractions x 22 fractions, given 5 times per week (total dose: 39.6 Gy)

1 treatment course patient is restaged 4 weeks after completion of radiation with "examination under anesthesia, cystoscopy with tumor-site biopsy, and urinary cytology." Patients not in complete remission usually proceeded to cystectomy. Patients in compete remission usually proceeded to consolidation therapy.

Consolidation therapy

Cisplatin (Platinol) 100 mg/m² IV once on day 1
Concurrent radiation therapy, 1.8 Gy fractions x 14 fractions, given 5 times per week (total dose in consolidation phase: 39.6 Gy; total overall dose in induction and consolidation phases: 64.8 Gy)

3-week course

Regimen #2, weekly cisplatin

Study	Evidence
Zapatero et al. 2000	Non-randomized

Patients had T2 to T4 N0 M0 disease.

Induction therapy

Cisplatin (Platinol) 20 mg/m² IV over 30 minutes once per day on days 1, 2, 8, 9, 15, 16 (per Figure 1 of Zapatero, et al. 2010), given before radiation therapy.
Concurrent radiation therapy according to one of the following:
- Accelerated hyperfractionated RT (AHFRT) 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." Radiation therapy given 5 days per week; treatment on days 1 to 5, 8 to 12, 15 to 16. Total induction dose to bladder tumor: 40.8 Gy; total induction dose to regional lymph nodes: 21.6 Gy.
- Normo-fractionated concurrent radiation therapy, 1.8 to 2 Gy fractions, given 5 times per week. Total induction and consolidation bladder dose of 64 to 66 Gy; total induction and consolidation pelvic lymph node dose of 44 to 46 Gy. Zapatero, et al. 2010 & Zapatero, et al. 2012 did not specify how much of this dose was given during induction therapy vs. consolidation therapy, nor what adjustments, if any, were made to chemotherapy for this radiation schedule.

16-day course of therapy (for AHFRT). 3 weeks after finishing radiation and chemotherapy, patients underwent restaging TURBT. Patient with complete regression (R0) continued to consolidation therapy. Nonresponders proceeded to cystectomy.

Consolidation therapy

Cisplatin (Platinol) 20 mg/m² IV over 30 minutes once per day on days 1, 2, 8, 9 (per Figure 1 of Zapatero, et al. 2010), given before radiation therapy.
Concurrent radiation therapy according to one of the following:
- Accelerated hyperfractionated RT (AHFRT), 1.5 Gy fractions twice per day x 16 fractions, treatment given on days 1 to 5, 8 to 10 (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.
- Normo-fractionated concurrent radiation therapy, 1.8 to 2 Gy fractions, given 5 times per week. Total induction and consolidation bladder dose of 64 to 66 Gy; total induction and consolidation pelvic lymph node dose of 44 to 46 Gy. Zapatero, et al. 2010 & Zapatero, et al. 2012 did not specify how much of this dose was given during induction therapy vs. consolidation therapy, nor what adjustments, if any, were made to chemotherapy for this radiation schedule.

16-day course of therapy (for AHFRT)

References

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 verified protocol PubMed
1. 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 Nov 3. link to original article contains verified protocol PubMed
Zapatero A, Martin 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 verified protocol PubMed
1. Update: Zapatero A, Martin 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 verified protocol PubMed

Fluorouracil, Cisplatin, RT

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Regimen

Study	Evidence
Kaufman, et al. 2000 (RTOG 95-06)	Phase I/II

Patients in RTOG 95-06 had clinical T2 to T4a Nx M0 disease without hydronephrosis and creatinine clearance of at least 60 mL/min.

Induction therapy

Fluorouracil (5-FU) 400 mg/m² IV push once per day on days 1 to 3, 15 to 17, given first, before radiation and cisplatin
Cisplatin (Platinol) 15 mg/m² IV over 1 hour once per day on days 1 to 3, 15 to 17, given second, before radiation
Concurrent radiation therapy, 3 Gy fractions twice per day, 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, given on days 1, 3, 15, 17 (total induction dose: 24 Gy), administered to the whole bladder, bladder tumor volume, and pelvic lymph nodes

Dose modifications

Patients with grade III hematologic toxicity, defined as platelets <50,000 or ANC <1800, had chemotherapy and radiation therapy held for at least one week, with therapy resuming when platelets were at least 100,000 and ANC at least 1800.

Supportive medications

IV hydration at 500 mL/H (no total volume specified) prior to fluorouracil

17-day course, then followed by repeat cystoscopy, biopsy, and urine cytology in week 7 or 8. Patients with complete response proceeded to consolidation chemotherapy/radiation in week 9. Incomplete responders were recommended to undergo radical cystectomy.

Consolidation therapy

Starts on week 9.

Fluorouracil (5-FU) 400 mg/m² IV push once per day on days 1 to 3, 15 to 17, given first, before radiation and cisplatin
Cisplatin (Platinol) 15 mg/m² IV over 1 hour once per day on days 1 to 3, 15 to 17, given second, before radiation
Concurrent radiation therapy, 2.5 Gy fractions twice per day, with at least 4 hours between fractions, x 8 fractions, given on days 1, 3, 15, 17 (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.

Dose modifications

Patients with grade III hematologic toxicity, defined as platelets <50,000 or ANC <1800, had chemotherapy and radiation therapy held for at least one week, with therapy resuming when platelets were at least 100,000 and ANC at least 1800.

Supportive medications

IV hydration at 500 mL/H (no total volume specified) prior to fluorouracil

17-day course

References

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 verified protocol 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 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 Nov 3. link to original article contains verified protocol PubMed

Fluorouracil, Mitomycin, RT

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RT: Radiation Therapy

Regimen

Study	Evidence	Comparator	Efficacy
James et al. 2012 (BC2001)	Phase III	Radiation therapy	Seems to have superior locoregional DFS

Chemoradiotherapy

Fluorouracil (5-FU) 500 mg/m²/day IV continuous infusion for 10 total days (total dose: 5000 mg/m²) during radiation fractions 1 to 5, 16 to 20
Mitomycin (Mutamycin) 12 mg/m² IV bolus once on day 1
Radiation therapy given according to one of the following plans:
- Concurrent radiation therapy, 2.75 Gy fractions x 20 fractions (total dose: 55 Gy) over 4 weeks
- Concurrent radiation therapy, 2 Gy fractions x 32 fractions (total dose: 64 Gy) over 6.5 weeks

References

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 verified protocol PubMed

Paclitaxel & RT

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Regimen

Study	Evidence
Zapatero et al. 2012	Non-randomized, <20 pts

Patients who had "mild renal insufficiency" received paclitaxel instead of cisplatin and had T2 to T4 N0 M0 disease.

Induction therapy

Paclitaxel (Taxol) 50 mg/m² IV once per week, given 6 hours before radiation therapy
Concurrent radiation therapy according to one of the following:
- Accelerated hyperfractionated RT (AHFRT) 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.
- Normo-fractionated 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.

3 weeks after finishing radiation and chemotherapy, patients underwent restaging TURBT. Patient with complete regression (R0) continued to consolidation therapy. Nonresponders proceeded to cystectomy.

Consolidation therapy

Paclitaxel (Taxol) 50 mg/m² IV once per week, given 6 hours before radiation therapy
Concurrent radiation therapy according to one of the following:
- Accelerated hyperfractionated RT (AHFRT), 1.5 Gy fractions twice per day x 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.
- Normo-fractionated 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.

References

Zapatero A, Martin 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 verified protocol PubMed

Radiation therapy

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Regimen

Study	Evidence	Comparator	Efficacy
James et al. 2012 (BC2001)	Phase III	Fluorouracil, Mitomycin, RT	Seems to have inferior locoregional DFS

Included here for reference purposes only.

References

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 verified protocol PubMed

Adjuvant chemotherapy

Observation

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Regimen

Study	Evidence	Comparator	Efficacy
Paz-Ares et al 2010 (SOGUG 99/01)	Phase III	PGC	Inferior OS

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

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 verified protocol

PGC

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PGC: Paclitaxel, Gemcitabine, Cisplatin

Regimen

Study	Evidence	Comparator	Efficacy
Paz-Ares et al 2010 (SOGUG 99/01)	Phase III	Observation	Superior OS

Patients in SOGUG 99/01 had pT3-4 and/or pN positive disease with adequate renal function (CrCl > 50 ml/min). The study prematurely closed due to poor recruitment and lacks adequate power to make firm conclusions.

Patients initially underwent cystectomy; the median time treatment started post-cystectomy was 48 days.

Chemotherapy

Paclitaxel (Taxol) 80 mg mg/2 IV oncer 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 verified protocol

Concurrent chemotherapy & radiation -> adjuvant chemotherapy

Cisplatin & RT -> MCV

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MCV: Methotrexate, Cisplatin, Vinblastine

Regimen

Study	Evidence
Hagan, et al. 2003 (RTOG 97-06)	Phase I/II

Patients in RTOG 97-06 had T2 to T4a N0 M0 disease without hydronephrosis.

Induction therapy

Patients initially underwent "aggressive transurethral resection of bladder tumor (TURBT)".

Cisplatin (Platinol) 20 mg/m² IV over 30 minutes once per day on days 1, 2, 8, 9, 15, 16, given before radiation therapy.
Accelerated concurrent radiation therapy, 1.8 Gy fractions x 12 fractions to the bladder tumor, bladder, and regional lymph nodes; 4 to 6 hours later, a 1.6 Gy fraction x 12 fractions is given to the tumor plus a 2 cm margin. Radiation therapy given 5 days per week; treatment on days 1 to 5, 8 to 12, 15 to 16. Total induction dose to bladder tumor: 40.8 Gy; total induction dose to regional lymph nodes: 21.6 Gy.

16-day course. 3 weeks after chemotherapy & radiation, patients were restaged with cystoscopy, tumor site biopsy, and urine cytology. Patients with complete response proceeded to consolidation therapy. Patients who did not achieve complete response proceeded to cystectomy.

Consolidation therapy

Cisplatin (Platinol) 20 mg/m² IV over 30 minutes once per day on days 1, 2, 8, 9, given before radiation therapy.

Concurrent radiation therapy according to one of the following:

Accelerated concurrent radiation therapy, 1.5 Gy fractions twice per day x 16 fractions, treatment given on days 1 to 5, 8 to 10 (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.

10-day course

Adjuvant MCV

Begins 8 weeks after initial therapy. Only 45% of patients in Hagan, et al. 2003 (RTOG 97-06) were able to complete 3 cycles of MCV

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

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 verified protocol 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 PubMed content property of HemOnc.org
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 Nov 3. link to original article contains verified protocol PubMed

Cisplatin, Paclitaxel, RT --> Cisplatin & Gemcitabine

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Regimen

Study	Evidence
Kaufman, et al. 2009 (RTOG 99-06)	Phase I/II

Induction therapy

Starts 4 to 6 weeks after transurethral resection of bladder tumor.

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
Concurrent radiation therapy, with BID RT on days 1 to 5, 8 to 12, 15 to 17; 4 to 6 hours between radiation sessions. Kaufman et al. 2009 (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 radiation as follows:
- 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. On week 7, over 3 weeks after induction therapy, patients under reevaluation with exam under anesthesia, cystoscopy with tumor site biopsy, and urine cytology. Patients with less than stage T1 disease proceeded to consolidation therapy. Patients with at least Stage T1 disease proceeded to radical cystectomy, followed by adjuvant chemotherapy. Note: The abstract of Kaufman, et al. 2009 (RTOG 99-06) 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 T1 disease.

Consolidation therapy

Starts on week 8.

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
Concurrent radiation therapy, 1.5 Gy fractions x 16 fractions, given twice per day (4 to 6 hour interval between treatments) on days 1 to 5, 8 to 10. 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

Adjuvant therapy

Starts "12 weeks after consolidation chemoradiotherapy, or 8 weeks after cystectomy."

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

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. link to original article contains verified protocol PubMed
1. 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 Nov 3. link to original article contains verified protocol PubMed

Cisplatin, Paclitaxel, RT --> Cisplatin, Gemcitabine, Paclitaxel

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Regimen

Study	Evidence	Comparator	Efficacy
Mitin et al. 2013 (RTOG 02-33)	Randomized Phase II	Fluorouracil, Cisplatin, RT --> Cisplatin, Gemcitabine, Paclitaxel	Not reported

Induction therapy

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
Concurrent radiation therapy, with BID RT, 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. On week 7, patients under reevaluation for response. Patients with less than stage T1 disease proceeded to consolidation therapy. Patients with at least stage T1 disease proceeded to radical cystectomy on week 9, followed by adjuvant chemotherapy.

Consolidation therapy

Starts on week 8.

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
Concurrent radiation therapy, 1.5 Gy fractions x 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

Adjuvant therapy

"Adjuvant chemotherapy began 12 weeks after consolidation chemoradiotherapy or 8 weeks after cystectomy."

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
Paclitaxel (Taxol) 50 mg/m² IV once per day on days 1 & 8

21-day cycle for 4 cycles

References

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. link to PMC article contains verified protocol PubMed
1. 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 Nov 3. link to original article contains verified protocol PubMed

Fluorouracil, Cisplatin, RT --> Cisplatin, Gemcitabine, Paclitaxel

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Regimen

Study	Evidence	Comparator	Efficacy
Mitin et al. 2013 (RTOG 02-33)	Randomized Phase II	Cisplatin, Paclitaxel, RT --> Cisplatin, Gemcitabine, Paclitaxel	Not reported

Induction therapy

Fluorouracil (5-FU) 400 mg/m² IV once per day on days 1 to 3, 8 to 10, 15 to 17
Cisplatin (Platinol) 15 mg/m² IV once per day on days 1 to 3, 8 to 10, 15 to 17
Concurrent radiation therapy, with BID RT, 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. On week 7, patients under reevaluation for response. Patients with less than stage T1 disease proceeded to consolidation therapy. Patients with at least stage T1 disease proceeded to radical cystectomy on week 9, followed by adjuvant chemotherapy.

Consolidation therapy

Starts on week 8.

Fluorouracil (5-FU) 400 mg/m² IV once per day on days 1 to 3, 8 to 10
Cisplatin (Platinol) 15 mg/m² IV once per day on days 1, 2, 8, 9
Concurrent radiation therapy, 1.5 Gy fractions x 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

Adjuvant therapy

"Adjuvant chemotherapy began 12 weeks after consolidation chemoradiotherapy or 8 weeks after cystectomy."

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
Paclitaxel (Taxol) 50 mg/m² IV once per day on days 1 & 8

21-day cycle for 4 cycles

References

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. link to PMC article contains verified protocol PubMed
1. 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 Nov 3. link to original article contains verified protocol PubMed

Locally advanced or metastatic disease

Atezolizumab (Tecentriq)

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Regimen

Study	Evidence	ORR
Rosenberg et al. 2016	Phase II	15% (95% CI 11-20%)

Immunotherapy

Atezolizumab (Tecentriq) 1200 mg IV once on day 1

3-week cycles

References

Rosenberg JE, Hoffman-Censits J, Powles T, van der Heijden MS, Balar AV, Necchi A, Dawson N, O'Donnell PH, Balmanoukian A, Loriot Y, Srinivas S, Retz MM, Grivas P, Joseph RW, Galsky MD, Fleming MT, Petrylak DP, Perez-Gracia JL, Burris HA, Castellano D, Canil C, Bellmunt J, Bajorin D, Nickles D, Bourgon R, Frampton GM, Cui N, Mariathasan S, Abidoye O, Fine GD, Dreicer R. Atezolizumab in patients with locally advanced and metastatic urothelial carcinoma who have progressed following treatment with platinum-based chemotherapy: a single-arm, multicentre, phase 2 trial. Lancet. 2016 Mar 4. [Epub ahead of print] link to original article contains protocol PubMed

Carboplatin & Gemcitabine (GC)

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GC: Gemcitabine, Carboplatin

Regimen

Study	Evidence	ORR	Comparator	Comparator ORR	Efficacy	Pt Population
Dogliotti et al. 2006	Randomized Phase II	Intention to treat: 40% (95% CI NR) Evaluable patients only: 56% (95% CI: 40–72)	Cisplatin & Gemcitabine	Intention to treat: 49% (95% CI NR) Evaluable patients only: 66% (95% CI: 49–80)	Seems not superior	Chemo-naive

Chemotherapy

Carboplatin (Paraplatin) AUC 5 IV over 30 to 60 minutes once on day 2
Gemcitabine (Gemzar) 1250 mg/m² IV over 30 to 60 minutes once per day on days 1 & 8

21-day cycle for up to 6 cycles

References

Dogliotti L, Cartenì G, Siena S, Bertetto O, Martoni A, Bono A, Amadori D, Onat H, Marini L. Gemcitabine plus cisplatin versus gemcitabine plus carboplatin as first-line chemotherapy in advanced transitional cell carcinoma of the urothelium: results of a randomized phase 2 trial. Eur Urol. 2007 Jul;52(1):134-41. Epub 2006 Dec 26. link to SD article contains verified protocol PubMed

Carboplatin & Paclitaxel

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Regimen

Study	Evidence	ORR	Pt Population
Vaughn et al. 2002 (ECOG E2896)	Phase II	24% (95% CI 12-42%)	Chemo-naive

Chemotherapy

Carboplatin (Paraplatin) AUC 6 IV once on day 1
Paclitaxel (Taxol) 225 mg/m² IV over 3 hours once on day 1

21-day cycle for up to 6 cycles

References

Vaughn DJ, Manola J, Dreicer R, See W, Levitt R, Wilding G. Phase II study of paclitaxel plus carboplatin in patients with advanced carcinoma of the urothelium and renal dysfunction (E2896): a trial of the Eastern Cooperative Oncology Group. Cancer. 2002 Sep 1;95(5):1022-7. link to original article contains protocol PubMed

CISCA

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CISCA: CISplatin, Cyclophosphamide, Adriamycin (Doxorubicin)

Regimen

Study	Evidence	ORR	Comparator	Comparator ORR	Efficacy	Pt Population
Logothetis et al. 1990	Phase III	46% (95% CI 32-62%)	MVAC	65% (95% CI 52-77%)	Inferior OS	Chemo-naive

Chemotherapy

Cyclophosphamide (Cytoxan) 650 mg/m² IV once on day 1
Cisplatin (Platinol) 100 mg/m² IV once on day 2
Doxorubicin (Adriamycin) 50 mg/m² IV once on day 2

Supportive medications

Forced mannitol diuresis with cisplatin

21-day cycle for up to 6 cycles

References

Logothetis CJ, Dexeus FH, Finn L, Sella A, Amato RJ, Ayala AG, Kilbourn RG. A prospective randomized trial comparing MVAC and CISCA chemotherapy for patients with metastatic urothelial tumors. J Clin Oncol. 1990 Jun;8(6):1050-5. link to original article contains verified protocol PubMed

Cisplatin & Gemcitabine (GC/GP)

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GC: Gemcitabine, Cisplatin
GP: Gemcitabine, Platinol (Cisplatin)

Regimen #1, 4-week schedule

Study	Evidence	Comparator	Efficacy
von der Maase et al. 2000	Phase III	MVAC	Seems not superior
Soto Parra et al. 2002	Randomized Phase II, <20 pts in this subgroup	Cisplatin & Gemcitabine, 3-week schedule, gemcitabine at 1000 mg/m²	Not reported
Bellmunt et al. 2012 (EORTC 30987)	Phase III	PCG	Might have inferior OS

Only a minority of patients in Soto Parra et al. 2002 had bladder cancer. The majority of patients had non-small cell lung cancer.

Chemotherapy

Cisplatin (Platinol) 70 mg/m² IV over 30 to 60 minutes once on day 2
Gemcitabine (Gemzar) 1000 mg/m² IV over 30 to 60 minutes once per day on days 1, 8, 15

Supportive medications

Per Soto Parra et al. 2002:
2 liters of fluid and "appropriate antiemetic therapy" given with cisplatin
"blood-product transfusion and the administration of antibiotics, antiemetics and analgesics, as appropriate"

28-day cycle for up to 6 cycles, progression of disease, unacceptable toxicity, or physician discretion based on patient's best interests

Regimen #2, 3-week schedule, gemcitabine at 1250 mg/m²

Study	Evidence	ORR	Comparator	Comparator ORR	Efficacy	Pt Population
Dogliotti et al. 2006	Randomized Phase II	Intention to treat: 49% (95% CI NR) Evaluable patients only: 66% (95% CI: 49–80)	Carboplatin & Gemcitabine	Intention to treat: 40% (95% CI NR) Evaluable patients only: 56% (95% CI: 40–72)	Seems not superior	Chemo-naive

Chemotherapy

Cisplatin (Platinol) 70 mg/m² IV once on day 2
Gemcitabine (Gemzar) 1250 mg/m² IV over 30 to 60 minutes once per day on days 1 & 8

21-day cycle for up to 6 cycles, until progression of disease, unacceptable toxicity, or physician discretion based on patient's best interests

Regimen #3, 3-week schedule, gemcitabine at 1000 mg/m²

Study	Evidence	Comparator	Efficacy	Pt Population
Soto Parra et al. 2002	Randomized Phase II, <20 pts in this subgroup	Cisplatin & Gemcitabine, 4-week schedule	Not reported	Chemo-naive

Chemotherapy

Cisplatin (Platinol) 70 mg/m² IV over 30 to 60 minutes once on day 2
Gemcitabine (Gemzar) 1000 mg/m² IV once per day on days 1 & 8

Supportive medications

2 liters of fluid and "appropriate antiemetic therapy" given with cisplatin
"blood-product transfusion and the administration of antibiotics, antiemetics and analgesics, as appropriate"

21-day cycle for up to 6 cycles, progression of disease, unacceptable toxicity, or physician discretion based on patient's best interests

References

von der Maase H, Hansen SW, Roberts JT, Dogliotti L, Oliver T, Moore MJ, Bodrogi I, Albers P, Knuth A, Lippert CM, Kerbrat P, Sanchez Rovira P, Wersall P, Cleall SP, Roychowdhury DF, Tomlin I, Visseren-Grul CM, Conte PF. Gemcitabine and cisplatin versus methotrexate, vinblastine, doxorubicin, and cisplatin in advanced or metastatic bladder cancer: results of a large, randomized, multinational, multicenter, phase III study. J Clin Oncol. 2000 Sep;18(17):3068-77. link to original article contains verified protocol PubMed
Soto Parra H, Cavina R, Latteri F, Sala A, Dambrosio M, Antonelli G, Morenghi E, Alloisio M, Ravasi G, Santoro A. Three-week versus four-week schedule of cisplatin and gemcitabine: results of a randomized phase II study. Ann Oncol. 2002 Jul;13(7):1080-6. link to original article contains verified protocol PubMed
Dogliotti L, Cartenì G, Siena S, Bertetto O, Martoni A, Bono A, Amadori D, Onat H, Marini L. Gemcitabine plus cisplatin versus gemcitabine plus carboplatin as first-line chemotherapy in advanced transitional cell carcinoma of the urothelium: results of a randomized phase 2 trial. Eur Urol. 2007 Jul;52(1):134-41. Epub 2006 Dec 26. link to SD article contains verified protocol PubMed
Bellmunt J, von der Maase H, Mead GM, Skoneczna I, De Santis M, Daugaard G, Boehle A, Chevreau C, Paz-Ares L, Laufman LR, Winquist E, Raghavan D, Marreaud S, Collette S, Sylvester R, de Wit R. Randomized Phase III Study Comparing Paclitaxel/Cisplatin/ Gemcitabine and Gemcitabine/Cisplatin in Patients With Locally Advanced or Metastatic Urothelial Cancer Without Prior Systemic Therapy: EORTC Intergroup Study 30987. J Clin Oncol. 2012 Apr 1;30(10):1107-13. Epub 2012 Feb 27. link to original article contains verified protocol PubMed

Cisplatin, Gemcitabine, Paclitaxel (PCG)

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PCG: Paclitaxel, Cisplatin, Gemcitabine

Regimen

Study	Evidence	ORR	Comparator	Comparator ORR	Efficacy	Pt Population
Bellmunt et al. 2012 (EORTC 30987)	Phase III	56% (95% CI NR)	Cisplatin & Gemcitabine	44% (95% CI NR)	Might have superior OS	Chemo-naive

Chemotherapy

Cisplatin (Platinol) 70 mg/m² IV once on day 1
Gemcitabine (Gemzar) 1000 mg/m² IV over 30 to 60 minutes once per day on days 1 & 8
Paclitaxel (Taxol) 80 mg/m² IV once per day on days 1 & 8, given first

21-day cycle for up to 6 cycles

References

Bellmunt J, von der Maase H, Mead GM, Skoneczna I, De Santis M, Daugaard G, Boehle A, Chevreau C, Paz-Ares L, Laufman LR, Winquist E, Raghavan D, Marreaud S, Collette S, Sylvester R, de Wit R. Randomized Phase III Study Comparing Paclitaxel/Cisplatin/ Gemcitabine and Gemcitabine/Cisplatin in Patients With Locally Advanced or Metastatic Urothelial Cancer Without Prior Systemic Therapy: EORTC Intergroup Study 30987. J Clin Oncol. 2012 Apr 1;30(10):1107-13. Epub 2012 Feb 27. link to original article contains verified protocol PubMed

Docetaxel (Taxotere)

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Regimen

Study	Evidence	ORR	Comparator	Comparator ORR	Efficacy	Pt Population
Choueiri et al. 2012	Phase III	11% (95% CI NR)	Docetaxel & Vandetanib	7% (95% CI NR)	Seems not superior	Mix of chemo-naive and treated

Chemotherapy

Docetaxel (Taxotere) 75 mg/m² IV on day 1

21-day cycles

References

McCaffrey JA, Hilton S, Mazumdar M, Sadan S, Kelly WK, Scher HI, Bajorin DF. Phase II trial of docetaxel in patients with advanced or metastatic transitional-cell carcinoma. J Clin Oncol. 1997 May;15(5):1853-7. link to original article PubMed
Choueiri TK, Ross RW, Jacobus S, Vaishampayan U, Yu EY, Quinn DI, Hahn NM, Hutson TE, Sonpavde G, Morrissey SC, Buckle GC, Kim WY, Petrylak DP, Ryan CW, Eisenberger MA, Mortazavi A, Bubley GJ, Taplin ME, Rosenberg JE, Kantoff PW. Double-blind, randomized trial of docetaxel plus vandetanib versus docetaxel plus placebo in platinum-pretreated metastatic urothelial cancer. J Clin Oncol. 2012 Feb 10;30(5):507-12. link to original article PubMed

Gemcitabine & Paclitaxel

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Regimen

Study	Evidence	ORR	Pt Population
Meluch et al. 2001	Phase II	54% (95% CI 40-67%)	mix of chemo-naive and exposed (but not with gemcitabine or paclitaxel)

Chemotherapy

Gemcitabine (Gemzar) 1000 mg/m² IV once per day on days 1, 8, 15
Paclitaxel (Taxol) 200 mg/m² IV over 3 hours once on day 1

21-day cycle for up to 6 cycles

References

Meluch AA, Greco FA, Burris HA 3rd, O'Rourke T, Ortega G, Steis RG, Morrissey LH, Johnson V, Hainsworth JD. Paclitaxel and gemcitabine chemotherapy for advanced transitional-cell carcinoma of the urothelial tract: a phase II trial of the Minnie pearl cancer research network. J Clin Oncol. 2001 Jun 15;19(12):3018-24. link to original article PubMed

MVAC

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MVAC: Methotrexate, Vinblastine, Adriamycin, Cisplatin

Regimen #1, dose-dense

Study	Evidence	ORR	Comparator	Comparator ORR	Efficacy	Pt Population
Sternberg et al. 2001 (EORTC 30924)	Phase III	62% (95% CI 54-70%)	Standard MVAC	50% (95% CI 42-59%)	Seems to have superior PFS	Chemo-naive

Chemotherapy

Methotrexate (MTX) 30 mg/m² IV once on day 1
Vinblastine (Velban) 3 mg/m² IV once on day 2
Doxorubicin (Adriamycin) 30 mg/m² IV once on day 2
Cisplatin (Platinol) 70 mg/m² IV once on day 2

Supportive medications

G-CSF 240 ug/m² SC once per day on days 4 to 10 (additional use up to a total of 14 consecutive days if needed), injected at alternating sites, discontinued if ANC >30 x 10⁹/L.
- In contrast to Sternberg et al. 2001, Sternberg et al. 2006 said G-CSF was given on days 3 to 7.

14-day cycles, given until progression of disease or unacceptable toxicity

In contrast to Sternberg et al. 2001, Sternberg et al. 2006 specified 15-day cycles

Regimen #2, standard

Study	Evidence	Comparator	Efficacy
Logothetis et al. 1990	Phase III	CISCA	Superior OS
von der Maase et al. 2000	Phase III	Cisplatin & Gemcitabine	Seems not superior
Sternberg et al. 2001 (EORTC 30924)	Phase III	Dose-dense MVAC	Seems to have inferior PFS
Han et al. 2008	Phase II

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 cycles (number of cycles and criteria to continue therapy varies depending on reference)

References

Logothetis CJ, Dexeus FH, Finn L, Sella A, Amato RJ, Ayala AG, Kilbourn RG. A prospective randomized trial comparing MVAC and CISCA chemotherapy for patients with metastatic urothelial tumors. J Clin Oncol. 1990 Jun;8(6):1050-5. link to original article contains verified protocol PubMed
von der Maase H, Hansen SW, Roberts JT, Dogliotti L, Oliver T, Moore MJ, Bodrogi I, Albers P, Knuth A, Lippert CM, Kerbrat P, Sanchez Rovira P, Wersall P, Cleall SP, Roychowdhury DF, Tomlin I, Visseren-Grul CM, Conte PF. Gemcitabine and cisplatin versus methotrexate, vinblastine, doxorubicin, and cisplatin in advanced or metastatic bladder cancer: results of a large, randomized, multinational, multicenter, phase III study. J Clin Oncol. 2000 Sep;18(17):3068-77. link to original article contains verified protocol PubMed
Sternberg CN, de Mulder PH, Schornagel JH, Théodore C, Fossa SD, van Oosterom AT, Witjes F, Spina M, van Groeningen CJ, de Balincourt C, Collette L; European Organization for Research and Treatment of Cancer Genitourinary Tract Cancer Cooperative Group. Randomized phase III trial of high-dose-intensity methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC) chemotherapy and recombinant human granulocyte colony-stimulating factor versus classic MVAC in advanced urothelial tract tumors: European Organization for Research and Treatment of Cancer Protocol no. 30924. J Clin Oncol. 2001 May 15;19(10):2638-46. link to original article contains verified protocol PubMed
1. Update: Sternberg CN, de Mulder P, Schornagel JH, Theodore C, Fossa SD, van Oosterom AT, Witjes JA, Spina M, van Groeningen CJ, Duclos B, Roberts JT, de Balincourt C, Collette L; EORTC Genito-Urinary Cancer Group. Seven year update of an EORTC phase III trial of high-dose intensity M-VAC chemotherapy and G-CSF versus classic M-VAC in advanced urothelial tract tumours. Eur J Cancer. 2006 Jan;42(1):50-4. Epub 2005 Dec 5. link to SD article contains verified protocol PubMed
Han KS, Joung JY, Kim TS, Jeong IG, Seo HK, Chung J, Lee KH. Methotrexate, vinblastine, doxorubicin and cisplatin combination regimen as salvage chemotherapy for patients with advanced or metastatic transitional cell carcinoma after failure of gemcitabine and cisplatin chemotherapy. Br J Cancer. 2008 Jan 15;98(1):86-90. Epub 2007 Dec 18. link to original article contains verified protocol PubMed

Nab-paclitaxel (Abraxane)

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Regimen

Study	Evidence	ORR	Pt Population
Ko et al. 2013	Phase II	28% (95% CI 17-44%)	One prior platinum regimen

Chemotherapy

nab-paclitaxel (Abraxane) 260 mg/m² IV on day 1

21-day cycles

Dose modifications

"Two dose reductions were permitted, to 240 mg/m² and then to 180 mg/m². When further dose reductions were required, study treatment was discontinued. Patients with febrile neutropenia, or delay of cycle because of persistent neutropenia, neutropenia of less than 0·5 × 109/L for 1 week, or grade 3 or 4 thrombocytopenia required dose reductions. When sensory neuropathy of grade 2 or higher occurred, study drug was withheld until resolution to grade 2 or better, then reinstituted at the next lower dose. When mucositis or diarrhea of grade 3 or higher occurred, study drug was withheld until resolution to grade 1 or better, then reinstituted at the next lower dose. Patients with mucositis or diarrhea of grade 4 were removed from the trial."

References

Ko YJ, Canil CM, Mukherjee SD, Winquist E, Elser C, Eisen A, Reaume MN, Zhang L, Sridhar SS. Nanoparticle albumin-bound paclitaxel for second-line treatment of metastatic urothelial carcinoma: a single group, multicentre, phase 2 study. Lancet Oncol. 2013 Jul;14(8):769-76. link to original article contains protocol PubMed

Paclitaxel (Taxol)

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Regimen

Study	Evidence	ORR	Pt Population
Vaughn et al. 2002	Phase II	10% (95% CI 0-20%)	One prior regimen

Chemotherapy

Paclitaxel (Taxol) 80mg/m² IV over 60 minutes once per day on days 1, 8, 15

28-day cycles

References

Vaughn DJ, Broome CM, Hussain M, Gutheil JC, Markowitz AB. Phase II trial of weekly paclitaxel in patients with previously treated advanced urothelial cancer. J Clin Oncol. 2002 Feb 15;20(4):937-40. link to original article contains protocol [https://www.ncbi.nlm.nih.gov/pubmed/11844814 PubMed}

Pembrolizumab (Keytruda)

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Regimen

Study	Evidence	ORR	Comparator	Efficacy
Bellmunt et al. 2015 (KEYNOTE-045)	Phase III	24%	Paclitaxel 175 mg/m2 Q3wk docetaxel Vinflunine	TBD

On 10/21/2016 Merck announced that KEYNOTE-045 was closed early due to pembrolizumab demonstrating superior overall survival compared to chemotherapy.

Immunotherapy

Pembrolizumab (Keytruda) 10 mg/kg IV once on day 1

2-week cycles

References

Joaquim Bellmunt, Guru Sonpavde, Ronald De Wit, Toni K. Choueiri, Arlene O. Siefker-Radtke, Elizabeth R. Plimack, Nicole M. Lewis, Holly Brown, Yabing Mai, Christine K. Gause, David Ross Kaufman, Dean F. Bajorin. KEYNOTE-045: Randomized phase 3 trial of pembrolizumab (MK-3475) versus paclitaxel, docetaxel, or vinflunine for previously treated metastatic urothelial cancer. 2015 ASCO Annual Meeting abstract TPS4571. link to abstract
10/21/2016 Merck press release regarding early closure of KEYNOTE-045

Pemetrexed (Alimta)

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Regimen

Study	Evidence	ORR	Pt Population
Sweeney, et al. 2006	Phase II	28% (95% CI 16-43%)	One prior regimen

Chemotherapy

Pemetrexed (Alimta) 500 mg/m² IV over 10 minutes once on day 1

21-day cycles

References

Sweeney CJ, Roth BJ, Kabbinavar FF, Vaughn DJ, Arning M, Curiel RE, Obasaju CK, Wang Y, Nicol SJ, Kaufman DS. Phase II study of pemetrexed for second-line treatment of transitional cell cancer of the urothelium. J Clin Oncol. 2006 Jul 20;24(21):3451-7. link to original article contains protocol 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

[1] 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

[1]

@@ Line 1: / Line 1: @@
 '''Use of this site is subject to you reading and agreeing with the terms set forth in the [[HemOnc.org_-_A_Hematology_Oncology_Wiki:General_disclaimer|disclaimer]].'''
-Is there a regimen missing from this list?  Would you like to share a different dosage/schedule or an additional reference for a regimen?  Have you noticed an error?  Do you have an idea that will help the site grow to better meet your needs and the needs of many others?  You are [[How_to_contribute|invited to contribute to the site]].
+Is there a regimen missing from this list? Would you like to share a different dosage/schedule or an additional reference for a regimen? Have you noticed an error? Do you have an idea that will help the site grow to better meet your needs and the needs of many others? You are [[How_to_contribute|invited to contribute to the site]].
 {| class="wikitable" style="float:right; margin-right: 5px;"
 |-
-|<div style="background-color: #66FF66; border: 1px solid #808000; padding: 5px; {{border-radius|16px}}" align="right"><font size="4"><b>{{#ask: [[-Has subobject::{{FULLPAGENAME}}]]  |?Regimen |limit=10000|format=sum}} regimens on this page</b></font></div>
+|<div style="background-color: #66FF66; border: 1px solid #808000; padding: 5px; {{border-radius|16px}}" align="right"><font size="4"><b>{{#ask: [[-Has subobject::{{FULLPAGENAME}}]] |?Regimen |limit=10000|format=sum}} regimens on this page</b></font></div>
-<div style="background-color: #66CCFF; border: 1px solid #808000; padding: 5px; {{border-radius|16px}}"><font size="4"><b>{{#ask: [[-Has subobject::{{FULLPAGENAME}}]]  |?Variant |limit=10000|format=sum}} variants on this page</b></font></div>
+<div style="background-color: #66CCFF; border: 1px solid #808000; padding: 5px; {{border-radius|16px}}"><font size="4"><b>{{#ask: [[-Has subobject::{{FULLPAGENAME}}]] |?Variant |limit=10000|format=sum}} variants on this page</b></font></div>
 |}
 {{TOC limit|limit=3}}
@@ Line 23: / Line 23: @@
 |[[Levels_of_Evidence#Evidence|'''Evidence''']]
 |'''Comparator'''
+|[[Levels_of_Evidence#Efficacy|'''Efficacy''']]
 |-
 |[http://www.jurology.com/article/S0022-5347(05)67707-5/fulltext Lamm et al. 2000]
 |style="background-color:#00CD00"|Phase III
 |Intravesical & percutaneous BCG, without maintenance therapy
+|style="background-color:#00CD00"|Superior RFS
 |-
 |}
@@ Line 33: / Line 35: @@
 *[[Bacillus Calmette-Guerin (BCG)]] (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.).
+**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'''
 ====Maintenance therapy====
-''The authors were a bit unclear about the schedule of maintenance therapy.  This is our best interpretation of how the schedule was described.''
+''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-Guerin (BCG)]] (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.).
+**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'''
@@ Line 50: / Line 52: @@
 |[[Levels_of_Evidence#Evidence|'''Evidence''']]
 |'''Comparator'''
+|[[Levels_of_Evidence#Efficacy|'''Efficacy''']]
 |-
 |[http://www.jurology.com/article/S0022-5347(05)67707-5/fulltext Lamm et al. 2000]
 |style="background-color:#00CD00"|Phase III
 |Intravesical & percutaneous BCG, with maintenance therapy
+|style="background-color:#ff0000"|Inferior RFS
 |-
 |}
 ====Immunotherapy====
 *[[Bacillus Calmette-Guerin (BCG)]] (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.
+**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.).
+**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'''
@@ Line 68: / Line 72: @@
 |[[Levels_of_Evidence#Evidence|'''Evidence''']]
 |'''Comparator'''
+|[[Levels_of_Evidence#Efficacy|'''Efficacy''']]
+|-
+|rowspan=2|[http://www.sciencedirect.com/science/article/pii/S0302283807006537 Ojea et al. 2007 (CUETO study 95011)]
+|rowspan=2 style="background-color:#00CD00"|Phase III
+|[[Bladder_cancer#Mitomycin_.28Mutamycin.29|Mitomycin]]
+|style="background-color:#00CD00"|Superior DFS
 |-
-|[http://www.sciencedirect.com/science/article/pii/S0302283807006537 Ojea et al. 2007 (CUETO study 95011)]
+|Very-low-dose BCG
-|style="background-color:#00CD00"|Phase III
+|style="background-color:#eeee00"|Seems not superior
-|[[Bladder_cancer#Mitomycin_.28Mutamycin.29|Mitomycin]]<br> Very-low-dose BCG
 |-
 |}
@@ Line 87: / Line 96: @@
 ===References===
-# Martínez-Piñeiro JA, Jiménez León J, Martínez-Piñeiro L Jr, Fiter L, Mosteiro JA, Navarro J, García Matres MJ, Cárcamo P. Bacillus Calmette-Guerin versus doxorubicin versus thiotepa: a randomized prospective study in 202 patients with superficial bladder cancer. J Urol. 1990 Mar;143(3):502-6. [http://www.ncbi.nlm.nih.gov/pubmed/2106041 PubMed]
+# Martínez-Piñeiro JA, Jiménez León J, Martínez-Piñeiro L Jr, Fiter L, Mosteiro JA, Navarro J, García Matres MJ, Cárcamo P. Bacillus Calmette-Guerin versus doxorubicin versus thiotepa: a randomized prospective study in 202 patients with superficial bladder cancer. J Urol. 1990 Mar;143(3):502-6. [https://www.ncbi.nlm.nih.gov/pubmed/2106041 PubMed]
-# 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-Guerin 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. [http://www.jurology.com/article/S0022-5347(05)67707-5/fulltext link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/10737480 PubMed]
+# 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-Guerin 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. [http://www.jurology.com/article/S0022-5347(05)67707-5/fulltext link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/10737480 PubMed]
-# Sylvester RJ, van der MEIJDEN AP, Lamm DL. Intravesical bacillus Calmette-Guerin 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. [http://www.jurology.com/article/S0022-5347(05)64273-5/fulltext link to original article] [http://www.ncbi.nlm.nih.gov/pubmed/12394686 PubMed]
+# Sylvester RJ, van der MEIJDEN AP, Lamm DL. Intravesical bacillus Calmette-Guerin 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. [http://www.jurology.com/article/S0022-5347(05)64273-5/fulltext link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/12394686 PubMed]
-# 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 Group (Club Urológico Español De Tratamiento Oncológico). A multicentre, randomised prospective trial comparing three intravesical adjuvant therapies for intermediate-risk superficial bladder cancer: low-dose bacillus Calmette-Guerin (27 mg) versus very low-dose bacillus Calmette-Guerin (13.5 mg) versus mitomycin C. Eur Urol. 2007 Nov;52(5):1398-406. Epub 2007 Apr 27. [http://www.sciencedirect.com/science/article/pii/S0302283807006537 link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/17485161 PubMed]
+# 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 Group (Club Urológico Español De Tratamiento Oncológico). A multicentre, randomised prospective trial comparing three intravesical adjuvant therapies for intermediate-risk superficial bladder cancer: low-dose bacillus Calmette-Guerin (27 mg) versus very low-dose bacillus Calmette-Guerin (13.5 mg) versus mitomycin C. Eur Urol. 2007 Nov;52(5):1398-406. Epub 2007 Apr 27. [http://www.sciencedirect.com/science/article/pii/S0302283807006537 link to SD article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/17485161 PubMed]
 ==Doxorubicin (Adriamycin) {{#subobject:8034b6|Regimen=1}}==
@@ Line 103: / Line 112: @@
 |[[Levels_of_Evidence#Evidence|'''Evidence''']]
 |'''Comparator'''
+|[[Levels_of_Evidence#Efficacy|'''Efficacy''']]
 |-
-|[http://www.ncbi.nlm.nih.gov/pubmed/2106041 Martínez-Piñeiro et al. 1990]
+|rowspan=2|[https://www.ncbi.nlm.nih.gov/pubmed/2106041 Martínez-Piñeiro et al. 1990]
-|style="background-color:#00CD00"|Phase III
+|rowspan=2 style="background-color:#00CD00"|Phase III
-|[[Bladder_cancer#Bacillus_Calmette-Guerin_.28BCG.29|BCG]]<br> [[Bladder_cancer#Thiotepa_.28Thioplex.29|Thiotepa]]
+|[[Bladder_cancer#Bacillus_Calmette-Guerin_.28BCG.29|BCG]]
+|style="background-color:#ff0000"|Inferior RFS
+|-
+|[[Bladder_cancer#Thiotepa_.28Thioplex.29|Thiotepa]]
+|style="background-color:#d3d3d3"|Not reported
 |-
 |}
@@ Line 115: / Line 129: @@
 ===References===
-# Martínez-Piñeiro JA, Jiménez León J, Martínez-Piñeiro L Jr, Fiter L, Mosteiro JA, Navarro J, García Matres MJ, Cárcamo P. Bacillus Calmette-Guerin versus doxorubicin versus thiotepa: a randomized prospective study in 202 patients with superficial bladder cancer. J Urol. 1990 Mar;143(3):502-6. [http://www.ncbi.nlm.nih.gov/pubmed/2106041 PubMed]
+# Martínez-Piñeiro JA, Jiménez León J, Martínez-Piñeiro L Jr, Fiter L, Mosteiro JA, Navarro J, García Matres MJ, Cárcamo P. Bacillus Calmette-Guerin versus doxorubicin versus thiotepa: a randomized prospective study in 202 patients with superficial bladder cancer. J Urol. 1990 Mar;143(3):502-6. [https://www.ncbi.nlm.nih.gov/pubmed/2106041 PubMed]
 ==Mitomycin (Mutamycin) {{#subobject:2e5944|Regimen=1}}==
@@ Line 128: / Line 142: @@
 |[[Levels_of_Evidence#Evidence|'''Evidence''']]
 |'''Comparator'''
+|[[Levels_of_Evidence#Efficacy|'''Efficacy''']]
 |-
-|[http://www.sciencedirect.com/science/article/pii/S0302283807006537 Ojea et al. 2007 (CUETO study 95011)]
+|rowspan=2|[http://www.sciencedirect.com/science/article/pii/S0302283807006537 Ojea et al. 2007 (CUETO study 95011)]
-|style="background-color:#00CD00"|Phase III
+|rowspan=2 style="background-color:#00CD00"|Phase III
-|[[Bladder_cancer#Bacillus_Calmette-Guerin_.28BCG.29|Low-dose BCG]]<br> [[Bladder_cancer#Bacillus_Calmette-Guerin_.28BCG.29|Very-low-dose BCG]]
+|[[Bladder_cancer#Bacillus_Calmette-Guerin_.28BCG.29|Low-dose BCG]]
+|style="background-color:#ff0000"|Inferior DFS
+|-
+|[[Bladder_cancer#Bacillus_Calmette-Guerin_.28BCG.29|Very-low-dose BCG]]
+|style="background-color:#eeee00"|Seems not superior
 |-
 |}
@@ Line 147: / Line 166: @@
 ===References===
-# 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 Group (Club Urológico Español De Tratamiento Oncológico). A multicentre, randomised prospective trial comparing three intravesical adjuvant therapies for intermediate-risk superficial bladder cancer: low-dose bacillus Calmette-Guerin (27 mg) versus very low-dose bacillus Calmette-Guerin (13.5 mg) versus mitomycin C. Eur Urol. 2007 Nov;52(5):1398-406. Epub 2007 Apr 27. [http://www.sciencedirect.com/science/article/pii/S0302283807006537 link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/17485161 PubMed]
+# 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 Group (Club Urológico Español De Tratamiento Oncológico). A multicentre, randomised prospective trial comparing three intravesical adjuvant therapies for intermediate-risk superficial bladder cancer: low-dose bacillus Calmette-Guerin (27 mg) versus very low-dose bacillus Calmette-Guerin (13.5 mg) versus mitomycin C. Eur Urol. 2007 Nov;52(5):1398-406. Epub 2007 Apr 27. [http://www.sciencedirect.com/science/article/pii/S0302283807006537 link to SD article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/17485161 PubMed]
 ==Pirarubicin (THP) {{#subobject:d9be78|Regimen=1}}==
@@ Line 160: / Line 179: @@
 |[[Levels_of_Evidence#Evidence|'''Evidence''']]
 |'''Comparator'''
+|[[Levels_of_Evidence#Efficacy|'''Efficacy''']]
 |-
 |[http://jco.ascopubs.org/content/31/11/1422.long Ito et al. 2013 (THP Monotherapy Study Group Trial)]
 |style="background-color:#00CD00"|Phase III
 |[[Bladder_cancer#Placebo_or_observation|Observation]]
+|style="background-color:#00CD00"|Seems to have superior RFS
 |-
 |}
@@ Line 174: / Line 195: @@
 ===References===
-# 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. [http://jco.ascopubs.org/content/31/11/1422.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/23460707 PubMed]
+# 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. [http://jco.ascopubs.org/content/31/11/1422.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/23460707 PubMed]
-==Placebo or observation {{#subobject:680def|Regimen=1}}==
+==Placebo or observation==
 {| class="wikitable" style="float:right; margin-left: 5px;"
 |-
@@ Line 182: / Line 203: @@
 |}
-===Regimen {{#subobject:641077|Variant=1}}===
+===Regimen===
 {| border="1" style="text-align:center;" !align="left"
 |'''Study'''
 |[[Levels_of_Evidence#Evidence|'''Evidence''']]
 |'''Comparator'''
+|[[Levels_of_Evidence#Efficacy|'''Efficacy''']]
 |-
 |[http://jco.ascopubs.org/content/31/11/1422.long Ito et al. 2013]
 |style="background-color:#00CD00"|Phase III
 |[[Bladder_cancer#Pirarubicin_.28THP.29|Pirarubicin]]
+|style="background-color:#00CD00"|Seems to have inferior RFS
 |-
 |}
@@ Line 197: / Line 220: @@
 ===References===
-# 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. [http://jco.ascopubs.org/content/31/11/1422.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/23460707 PubMed]
+# 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. [http://jco.ascopubs.org/content/31/11/1422.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/23460707 PubMed]
 ==Thiotepa (Thioplex) {{#subobject:5b9d6c|Regimen=1}}==
@@ Line 210: / Line 233: @@
 |[[Levels_of_Evidence#Evidence|'''Evidence''']]
 |'''Comparator'''
+|[[Levels_of_Evidence#Efficacy|'''Efficacy''']]
+|-
+|rowspan=2|[https://www.ncbi.nlm.nih.gov/pubmed/2106041 Martínez-Piñeiro et al. 1990]
+|rowspan=2 style="background-color:#00CD00"|Phase III
+|[[Bladder_cancer#Bacillus_Calmette-Guerin_.28BCG.29|BCG]]
+|style="background-color:#ff0000"|Inferior RFS
 |-
-|[http://www.ncbi.nlm.nih.gov/pubmed/2106041 Martínez-Piñeiro et al. 1990]
+|[[Bladder_cancer#Doxorubicin_.28Adriamycin.29|Doxorubicin]]
-|style="background-color:#00CD00"|Phase III
+|style="background-color:#d3d3d3"|Not reported
-|[[Bladder_cancer#Bacillus_Calmette-Guerin_.28BCG.29|BCG]]<br> [[Bladder_cancer#Doxorubicin_.28Adriamycin.29|Doxorubicin]]
 |-
 |}
@@ Line 222: / Line 250: @@
 ===References===
-# Martínez-Piñeiro JA, Jiménez León J, Martínez-Piñeiro L Jr, Fiter L, Mosteiro JA, Navarro J, García Matres MJ, Cárcamo P. Bacillus Calmette-Guerin versus doxorubicin versus thiotepa: a randomized prospective study in 202 patients with superficial bladder cancer. J Urol. 1990 Mar;143(3):502-6. [http://www.ncbi.nlm.nih.gov/pubmed/2106041 PubMed]
+# Martínez-Piñeiro JA, Jiménez León J, Martínez-Piñeiro L Jr, Fiter L, Mosteiro JA, Navarro J, García Matres MJ, Cárcamo P. Bacillus Calmette-Guerin versus doxorubicin versus thiotepa: a randomized prospective study in 202 patients with superficial bladder cancer. J Urol. 1990 Mar;143(3):502-6. [https://www.ncbi.nlm.nih.gov/pubmed/2106041 PubMed]
 =Neoadjuvant chemotherapy=
@@ Line 237: / Line 265: @@
 |[[Levels_of_Evidence#Evidence|'''Evidence''']]
 |-
-|[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2585515/ Dash et al. 2008]
+|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2585515/ Dash et al. 2008]
 |style="background-color:#ff0000"|Retrospective
 |-
@@ Line 252: / Line 280: @@
 |[[Levels_of_Evidence#Evidence|'''Evidence''']]
 |-
-|[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2585515/ Dash et al. 2008]
+|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2585515/ Dash et al. 2008]
 |style="background-color:#ff0000"|Retrospective
 |-
@@ Line 264: / Line 292: @@
 ===References===
-# 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. [http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2585515/ link to PMC article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/18823036 PubMed]
+# 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. [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2585515/ link to PMC article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/18823036 PubMed]
 ==CMV; MCV {{#subobject:553fe2|Regimen=1}}==
@@ Line 279: / Line 307: @@
 |[[Levels_of_Evidence#Evidence|'''Evidence''']]
 |'''Comparator'''
+|[[Levels_of_Evidence#Efficacy|'''Efficacy''']]
 |-
-|[http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(99)02292-8/abstract International Collaboration of Trialists et al. 1999 (BA06  30894)]
+|[http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(99)02292-8/abstract International Collaboration of Trialists et al. 1999 (BA06 30894)]
 |style="background-color:#00CD00"|Phase III
 |[[Bladder_cancer#No_neoadjuvant_therapy|No neoadjuvant therapy]]
+|style="background-color:#00CD00"|Seems to have superior OS
 |-
 |}
@@ Line 296: / Line 326: @@
 ===References===
-# Neoadjuvant cisplatin, methotrexate, and vinblastine chemotherapy for muscle-invasive bladder cancer: a randomised controlled trial. International collaboration of trialists. Lancet. 1999 Aug 14;354(9178):533-40. Erratum in: Lancet 1999 Nov 6;354(9190):1650. [http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(99)02292-8/abstract link to original article] [http://www.ncbi.nlm.nih.gov/pubmed/10470696 PubMed]
+# Neoadjuvant cisplatin, methotrexate, and vinblastine chemotherapy for muscle-invasive bladder cancer: a randomised controlled trial. International collaboration of trialists. Lancet. 1999 Aug 14;354(9178):533-40. Erratum in: Lancet 1999 Nov 6;354(9190):1650. [http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(99)02292-8/abstract link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/10470696 PubMed]
-## '''Update:''' International Collaboration of Trialists; Medical Research Council Advanced Bladder Cancer Working Party (now the National Cancer Research Institute Bladder Cancer Clinical Studies Group); European Organisation for Research and Treatment of Cancer Genito-Urinary Tract Cancer Group; Australian Bladder Cancer Study Group; National Cancer Institute of Canada Clinical Trials Group; Finnbladder; Norwegian Bladder Cancer Study Group; Club Urologico Espanol de Tratamiento Oncologico Group, Griffiths G, Hall R, Sylvester R, Raghavan D, Parmar MK. 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. [http://jco.ascopubs.org/content/29/16/2171.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/21502557 PubMed]
+## '''Update:''' International Collaboration of Trialists; Medical Research Council Advanced Bladder Cancer Working Party (now the National Cancer Research Institute Bladder Cancer Clinical Studies Group); European Organisation for Research and Treatment of Cancer Genito-Urinary Tract Cancer Group; Australian Bladder Cancer Study Group; National Cancer Institute of Canada Clinical Trials Group; Finnbladder; Norwegian Bladder Cancer Study Group; Club Urologico Espanol de Tratamiento Oncologico Group, Griffiths G, Hall R, Sylvester R, Raghavan D, Parmar MK. 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. [http://jco.ascopubs.org/content/29/16/2171.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/21502557 PubMed]
 ==MVAC {{#subobject:701fbe|Regimen=1}}==
@@ Line 311: / Line 341: @@
 |[[Levels_of_Evidence#Evidence|'''Evidence''']]
 |'''Comparator'''
+|[[Levels_of_Evidence#Efficacy|'''Efficacy''']]
 |-
-|[http://www.nejm.org/doi/full/10.1056/NEJMoa022148 Grossman et al. 2003]
+|[http://www.nejm.org/doi/full/10.1056/NEJMoa022148 Grossman et al. 2003 (SWOG S8710)]
 |style="background-color:#00CD00"|Phase III
 |[[Bladder_cancer#No_neoadjuvant_therapy|No neoadjuvant therapy]]
+|style="background-color:#00CD00"|Might have superior OS
 |-
 |}
@@ Line 326: / Line 358: @@
 ===References===
-# 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. [http://www.nejm.org/doi/full/10.1056/NEJMoa022148 link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/12944571 PubMed]
+# 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. [http://www.nejm.org/doi/full/10.1056/NEJMoa022148 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/12944571 PubMed]
+# 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. [http://annonc.oxfordjournals.org/content/25/6/1192.long link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/24669010 PubMed]
 ==MVAC (dose-dense/accelerated) {{#subobject:3cb963|Regimen=1}}==
@@ Line 384: / Line 417: @@
 ===References===
 <!-- # Angela Q. Qu, Susanna J. Jacobus, Sabina Signoretti, Edward C. Stack, Katherine Maragaret Krajewski, Jonathan E. Rosenberg, Toni K. Choueiri. Phase II study of neoadjuvant dose-dense methotrexate, vinblastine, doxorubicin, and cisplatin (ddMVAC) chemotherapy in patients with muscle-invasive urothelial cancer (MI-UC): Pathologic and radiologic response, serum tumor markers, and DNA excision repair pathway biomarkers in relation to disease-free survival (DFS). 2013 ASCO Annual Meeting abstract 4530. [http://meetinglibrary.asco.org/content/117233-132 link to abstract] -->
-# 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. [http://jco.ascopubs.org/content/32/18/1889.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/24821883 PubMed]
+# 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. [http://jco.ascopubs.org/content/32/18/1889.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/24821883 PubMed]
-# 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. [http://jco.ascopubs.org/content/32/18/1895.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/24821881 PubMed]
+# 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. [http://jco.ascopubs.org/content/32/18/1895.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/24821881 PubMed]
-==No neoadjuvant therapy {{#subobject:6a1f0|Regimen=1}}==
+==No neoadjuvant therapy==
 {| class="wikitable" style="float:right; margin-left: 5px;"
 |-
@@ Line 393: / Line 426: @@
 |}
-===Regimen {{#subobject:ea492b|Variant=1}}===
+===Regimen===
 {| border="1" style="text-align:center;" !align="left"
 |'''Study'''
 |[[Levels_of_Evidence#Evidence|'''Evidence''']]
 |'''Comparator'''
+|[[Levels_of_Evidence#Efficacy|'''Efficacy''']]
 |-
-|[http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(99)02292-8/abstract International Collaboration of Trialists et al. 1999 (BA06  30894)]
+|[http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(99)02292-8/abstract International Collaboration of Trialists et al. 1999 (BA06 30894)]
 |style="background-color:#00CD00"|Phase III
 |[[Bladder_cancer#CMV.2C_MCV|CMV]]
+|style="background-color:#ff0000"|Seems to have inferior OS
 |-
-|[http://www.nejm.org/doi/full/10.1056/NEJMoa022148 Grossman et al. 2003]
+|[http://www.nejm.org/doi/full/10.1056/NEJMoa022148 Grossman et al. 2003 (SWOG S8710)]
 |style="background-color:#00CD00"|Phase III
 |[[Bladder_cancer#MVAC|MVAC]]
+|style="background-color:#ff0000"|Might have inferior OS
 |-
 |}
@@ Line 411: / Line 447: @@
 ===References===
-# Neoadjuvant cisplatin, methotrexate, and vinblastine chemotherapy for muscle-invasive bladder cancer: a randomised controlled trial. International collaboration of trialists. Lancet. 1999 Aug 14;354(9178):533-40. Erratum in: Lancet 1999 Nov 6;354(9190):1650. [http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(99)02292-8/abstract link to original article] [http://www.ncbi.nlm.nih.gov/pubmed/10470696 PubMed]
+# Neoadjuvant cisplatin, methotrexate, and vinblastine chemotherapy for muscle-invasive bladder cancer: a randomised controlled trial. International collaboration of trialists. Lancet. 1999 Aug 14;354(9178):533-40. Erratum in: Lancet 1999 Nov 6;354(9190):1650. [http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(99)02292-8/abstract link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/10470696 PubMed]
-## '''Update:''' International Collaboration of Trialists; Medical Research Council Advanced Bladder Cancer Working Party (now the National Cancer Research Institute Bladder Cancer Clinical Studies Group); European Organisation for Research and Treatment of Cancer Genito-Urinary Tract Cancer Group; Australian Bladder Cancer Study Group; National Cancer Institute of Canada Clinical Trials Group; Finnbladder; Norwegian Bladder Cancer Study Group; Club Urologico Espanol de Tratamiento Oncologico Group, Griffiths G, Hall R, Sylvester R, Raghavan D, Parmar MK. 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. [http://jco.ascopubs.org/content/29/16/2171.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/21502557 PubMed]
+## '''Update:''' International Collaboration of Trialists; Medical Research Council Advanced Bladder Cancer Working Party (now the National Cancer Research Institute Bladder Cancer Clinical Studies Group); European Organisation for Research and Treatment of Cancer Genito-Urinary Tract Cancer Group; Australian Bladder Cancer Study Group; National Cancer Institute of Canada Clinical Trials Group; Finnbladder; Norwegian Bladder Cancer Study Group; Club Urologico Espanol de Tratamiento Oncologico Group, Griffiths G, Hall R, Sylvester R, Raghavan D, Parmar MK. 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. [http://jco.ascopubs.org/content/29/16/2171.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/21502557 PubMed]
-# 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. [http://www.nejm.org/doi/full/10.1056/NEJMoa022148 link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/12944571 PubMed]
+# 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. [http://www.nejm.org/doi/full/10.1056/NEJMoa022148 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/12944571 PubMed]
+# 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. [http://annonc.oxfordjournals.org/content/25/6/1192.long link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/24669010 PubMed]
 =Neoadjuvant chemotherapy -> RT=
@@ Line 437: / Line 474: @@
 *[[Cisplatin (Platinol)]] 100 mg/m<sup>2</sup> IV once on day 1
-'''21-day cycle for 3 cycles'''; after 3 cycles of chemotherapy, patients underwent cystoscopy, biopsy, and abdominal CT.  Patients with complete response or who were not surgical candidates proceeded to radiation therapy which begins 4 to 6 weeks after completion of chemotherapy.  Otherwise, patients proceeded to cystectomy.
+'''21-day cycle for 3 cycles'''; after 3 cycles of chemotherapy, patients underwent cystoscopy, biopsy, and abdominal CT. Patients with complete response or who were not surgical candidates proceeded to radiation therapy which begins 4 to 6 weeks after completion of chemotherapy. Otherwise, patients proceeded to cystectomy.
 ====Radiation therapy portion====
 ''Radiation therapy starts 4 to 6 weeks after completion of chemotherapy.''
-*Patients who had complete response received radiation therapy, 2 Gy fractions given 5 days per week, with total bladder dose of 60 Gy.  Total dose to regional lymph nodes: 50 Gy.
+*Patients who had complete response received radiation therapy, 2 Gy fractions given 5 days per week, with total bladder dose of 60 Gy. Total dose to regional lymph nodes: 50 Gy.
-**Patients who did not have complete response received radiation therapy for a total dose to the bladder of 64 to 66 Gy.  No further details given about fractionation, schedule, or dose to lymph nodes.
+**Patients who did not have complete response received radiation therapy for a 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. [http://onlinelibrary.wiley.com/doi/10.1002/1097-0215%2820001020%2990:5%3C287::AID-IJC6%3E3.0.CO;2-9/full link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/11091353 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. [http://onlinelibrary.wiley.com/doi/10.1002/1097-0215%2820001020%2990:5%3C287::AID-IJC6%3E3.0.CO;2-9/full link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/11091353 PubMed]
-## '''Update:''' Zapatero A, Martin 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. [http://www.urologiconcology.org/article/S1078-1439%2809%2900029-5/abstract link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/19362865 PubMed]
+## '''Update:''' Zapatero A, Martin 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. [http://www.urologiconcology.org/article/S1078-1439%2809%2900029-5/abstract link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/19362865 PubMed]
-## '''Update:''' Zapatero A, Martin 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. [http://www.goldjournal.net/article/S0090-4295%2812%2900867-9/abstract link to original article] [http://www.ncbi.nlm.nih.gov/pubmed/22999456 PubMed]
+## '''Update:''' Zapatero A, Martin 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. [http://www.goldjournal.net/article/S0090-4295%2812%2900867-9/abstract link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/22999456 PubMed]
 =Neoadjuvant chemotherapy -> concurrent chemotherapy & radiation therapy=
@@ Line 463: / Line 500: @@
 |[[Levels_of_Evidence#Evidence|'''Evidence''']]
 |'''Comparator'''
+|[[Levels_of_Evidence#Efficacy|'''Efficacy''']]
 |-
 |[http://jco.ascopubs.org/content/16/11/3576.long Shipley et al. 1998 (RTOG 89-03)]
 |style="background-color:#00CD00"|Phase III
 |[[Bladder_cancer#Cisplatin_.26_RT|Cisplatin & RT]]
+|style="background-color:#eeee00"|Seems not superior
 |-
 |}
-''2 cycles of MCV did not increase the rate of complete response over standard induction chemoradiation therapy with cisplatin and radiation.''
 ====Neoadjuvant chemotherapy====
 *[[Methotrexate (MTX)]] 30 mg/m<sup>2</sup> IV once per day on days 0, 14, 21
@@ Line 476: / Line 513: @@
 *[[Cisplatin (Platinol)]] 70 mg/m<sup>2</sup> IV once on day 1
-'''28-day cycle for 2 cycles'''
+'''28-day cycle for 2 cycles, followed by:'''
-====Induction therapy====
+====Neoadjuvant chemoradiotherapy====
 *[[Cisplatin (Platinol)]] 100 mg/m<sup>2</sup> IV once per day on days 1 & 22
 *Concurrent radiation therapy, 1.8 Gy fractions x 22 fractions, given 5 times per week (total dose: 39.6 Gy)
-'''1 treatment course'''; patient is restaged 4 weeks after completion of radiation with "examination under anesthesia, cystoscopy with tumor-site biopsy, and urinary cytology."  Patients not in complete remission usually proceeded to cystectomy.  Patients in compete remission usually proceeded to consolidation therapy.
+'''1 treatment course'''; patient is restaged 4 weeks after completion of radiation with "examination under anesthesia, cystoscopy with tumor-site biopsy, and urinary cytology." Patients not in complete remission usually proceeded to cystectomy. Patients in compete remission usually proceeded to consolidation therapy.
 ====Consolidation therapy====
@@ Line 511: / Line 548: @@
 *Concurrent radiation therapy, 1.8 Gy fractions x 22 fractions (total dose: 39.6 Gy)
-'''1 treatment course'''; patient is restaged 2 weeks after completion of radiation with "examination under anesthesia, cystoscopy with tumor-site biopsy, urinary cytology, and computed tomographic scan of pelvis."  Patients with complete response--no evidence of disease on this evaluation--proceeded to consolidation radiotherapy.  Patients without complete response proceeded immediately to cystectomy.
+'''1 treatment course'''; patient is restaged 2 weeks after completion of radiation with "examination under anesthesia, cystoscopy with tumor-site biopsy, urinary cytology, and computed tomographic scan of pelvis." Patients with complete response--no evidence of disease on this evaluation--proceeded to consolidation radiotherapy. Patients without complete response proceeded immediately to cystectomy.
 ====Consolidation therapy====
@@ Line 520: / Line 557: @@
 ===References===
-# 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. [http://jco.ascopubs.org/content/14/1/119.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/8558186 PubMed]
+# 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. [http://jco.ascopubs.org/content/14/1/119.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/8558186 PubMed]
-# 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. [http://jco.ascopubs.org/content/16/11/3576.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/9817278 PubMed]
+# 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. [http://jco.ascopubs.org/content/16/11/3576.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/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. [http://jco.ascopubs.org/content/27/25/4055.long link to original article] [http://www.ncbi.nlm.nih.gov/pubmed/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. [http://jco.ascopubs.org/content/27/25/4055.long link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/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 Nov 3. [http://jco.ascopubs.org/content/32/34/3801.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/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 Nov 3. [http://jco.ascopubs.org/content/32/34/3801.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/25366678 PubMed]
 =Concurrent chemotherapy & radiation=
@@ Line 538: / Line 575: @@
 |[[Levels_of_Evidence#Evidence|'''Evidence''']]
 |'''Comparator'''
+|[[Levels_of_Evidence#Efficacy|'''Efficacy''']]
 |-
 |[http://jco.ascopubs.org/content/16/11/3576.long Shipley et al. 1998 (RTOG 89-03)]
 |style="background-color:#00CD00"|Phase III
 |[[Bladder_cancer#MCV_-.3E_Cisplatin_.26_RT|MCV -> Cisplatin & RT]]
+|style="background-color:#eeee00"|Seems not superior
 |-
 |}
-====Induction therapy====
+====Induction chemoradiotherapy====
 *[[Cisplatin (Platinol)]] 100 mg/m<sup>2</sup> IV once per day on days 1 & 22
 *Concurrent radiation therapy, 1.8 Gy fractions x 22 fractions, given 5 times per week (total dose: 39.6 Gy)
-'''1 treatment course''' patient is restaged 4 weeks after completion of radiation with "examination under anesthesia, cystoscopy with tumor-site biopsy, and urinary cytology."  Patients not in complete remission usually proceeded to cystectomy.  Patients in compete remission usually proceeded to consolidation therapy.
+'''1 treatment course''' patient is restaged 4 weeks after completion of radiation with "examination under anesthesia, cystoscopy with tumor-site biopsy, and urinary cytology." Patients not in complete remission usually proceeded to cystectomy. Patients in compete remission usually proceeded to consolidation therapy.
 ====Consolidation therapy====
@@ Line 570: / Line 609: @@
 *[[Cisplatin (Platinol)]] 20 mg/m<sup>2</sup> IV over 30 minutes once per day on days 1, 2, 8, 9, 15, 16 (per Figure 1 of Zapatero, et al. 2010), given before radiation therapy.
 *Concurrent radiation therapy according to one of the following:
-**Accelerated hyperfractionated RT (AHFRT) 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."  Radiation therapy given 5 days per week; treatment on days 1 to 5, 8 to 12, 15 to 16.  Total induction dose to bladder tumor: 40.8 Gy; total induction dose to regional lymph nodes: 21.6 Gy.
+**Accelerated hyperfractionated RT (AHFRT) 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." Radiation therapy given 5 days per week; treatment on days 1 to 5, 8 to 12, 15 to 16. Total induction dose to bladder tumor: 40.8 Gy; total induction dose to regional lymph nodes: 21.6 Gy.
-**Normo-fractionated concurrent radiation therapy, 1.8 to 2 Gy fractions, given 5 times per week.  Total induction and consolidation bladder dose of 64 to 66 Gy; total induction and consolidation pelvic lymph node dose of 44 to 46 Gy.  Zapatero, et al. 2010 & Zapatero, et al. 2012 did not specify how much of this dose was given during induction therapy vs. consolidation therapy, nor what adjustments, if any, were made to chemotherapy for this radiation schedule.
+**Normo-fractionated concurrent radiation therapy, 1.8 to 2 Gy fractions, given 5 times per week. Total induction and consolidation bladder dose of 64 to 66 Gy; total induction and consolidation pelvic lymph node dose of 44 to 46 Gy. Zapatero, et al. 2010 & Zapatero, et al. 2012 did not specify how much of this dose was given during induction therapy vs. consolidation therapy, nor what adjustments, if any, were made to chemotherapy for this radiation schedule.
-'''16-day course of therapy (for AHFRT).  3 weeks after finishing radiation and chemotherapy, patients underwent restaging TURBT.'''  Patient with complete regression (R0) continued to consolidation therapy.  Nonresponders proceeded to cystectomy.
+'''16-day course of therapy (for AHFRT). 3 weeks after finishing radiation and chemotherapy, patients underwent restaging TURBT.''' Patient with complete regression (R0) continued to consolidation therapy. Nonresponders proceeded to cystectomy.
 ====Consolidation therapy====
 *[[Cisplatin (Platinol)]] 20 mg/m<sup>2</sup> IV over 30 minutes once per day on days 1, 2, 8, 9 (per Figure 1 of Zapatero, et al. 2010), given before radiation therapy.
 *Concurrent radiation therapy according to one of the following:
-**Accelerated hyperfractionated RT (AHFRT), 1.5 Gy fractions twice per day x 16 fractions, treatment given on days 1 to 5, 8 to 10 (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.
+**Accelerated hyperfractionated RT (AHFRT), 1.5 Gy fractions twice per day x 16 fractions, treatment given on days 1 to 5, 8 to 10 (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.
-**Normo-fractionated concurrent radiation therapy, 1.8 to 2 Gy fractions, given 5 times per week.  Total induction and consolidation bladder dose of 64 to 66 Gy; total induction and consolidation pelvic lymph node dose of 44 to 46 Gy.  Zapatero, et al. 2010 & Zapatero, et al. 2012 did not specify how much of this dose was given during induction therapy vs. consolidation therapy, nor what adjustments, if any, were made to chemotherapy for this radiation schedule.
+**Normo-fractionated concurrent radiation therapy, 1.8 to 2 Gy fractions, given 5 times per week. Total induction and consolidation bladder dose of 64 to 66 Gy; total induction and consolidation pelvic lymph node dose of 44 to 46 Gy. Zapatero, et al. 2010 & Zapatero, et al. 2012 did not specify how much of this dose was given during induction therapy vs. consolidation therapy, nor what adjustments, if any, were made to chemotherapy for this radiation schedule.
 '''16-day course of therapy (for AHFRT)'''
 ===References===
-# 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. [http://jco.ascopubs.org/content/16/11/3576.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/9817278 PubMed]
+# 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. [http://jco.ascopubs.org/content/16/11/3576.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/9817278 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 Nov 3. [http://jco.ascopubs.org/content/32/34/3801.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/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 Nov 3. [http://jco.ascopubs.org/content/32/34/3801.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/25366678 PubMed]
-# Zapatero A, Martin 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. [http://www.urologiconcology.org/article/S1078-1439%2809%2900029-5/abstract link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/19362865 PubMed]
+# Zapatero A, Martin 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. [http://www.urologiconcology.org/article/S1078-1439%2809%2900029-5/abstract link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/19362865 PubMed]
-## '''Update:''' Zapatero A, Martin 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. [http://www.goldjournal.net/article/S0090-4295%2812%2900867-9/abstract link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/22999456 PubMed]
+## '''Update:''' Zapatero A, Martin 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. [http://www.goldjournal.net/article/S0090-4295%2812%2900867-9/abstract link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/22999456 PubMed]
 ==Fluorouracil, Cisplatin, RT {{#subobject:b5e26|Regimen=1}}==
@@ Line 617: / Line 656: @@
 *IV hydration at 500 mL/H (no total volume specified) prior to fluorouracil
-'''17-day course, then followed by repeat cystoscopy, biopsy, and urine cytology in week 7 or 8.'''  Patients with complete response proceeded to consolidation chemotherapy/radiation in week 9.  Incomplete responders were recommended to undergo radical cystectomy.
+'''17-day course, then followed by repeat cystoscopy, biopsy, and urine cytology in week 7 or 8.''' Patients with complete response proceeded to consolidation chemotherapy/radiation in week 9. Incomplete responders were recommended to undergo radical cystectomy.
 ====Consolidation therapy====
@@ Line 623: / Line 662: @@
 *[[Fluorouracil (5-FU)]] 400 mg/m<sup>2</sup> IV push once per day on days 1 to 3, 15 to 17, given first, before radiation and cisplatin
 *[[Cisplatin (Platinol)]] 15 mg/m<sup>2</sup> IV over 1 hour once per day on days 1 to 3, 15 to 17, given second, before radiation
-*Concurrent radiation therapy, 2.5 Gy fractions twice per day, with at least 4 hours between fractions, x 8 fractions, given on days 1, 3, 15, 17 (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.
+*Concurrent radiation therapy, 2.5 Gy fractions twice per day, with at least 4 hours between fractions, x 8 fractions, given on days 1, 3, 15, 17 (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.
 ====Dose modifications====
@@ Line 634: / Line 673: @@
 ===References===
-# 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. [http://theoncologist.alphamedpress.org/content/5/6/471.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/11110598 PubMed]
+# 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. [http://theoncologist.alphamedpress.org/content/5/6/471.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/11110598 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. [http://jco.ascopubs.org/content/27/25/4055.long link to original article] [http://www.ncbi.nlm.nih.gov/pubmed/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. [http://jco.ascopubs.org/content/27/25/4055.long link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/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 Nov 3. [http://jco.ascopubs.org/content/32/34/3801.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/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 Nov 3. [http://jco.ascopubs.org/content/32/34/3801.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/25366678 PubMed]
 ==Fluorouracil, Mitomycin, RT {{#subobject:5e89d1|Regimen=1}}==
@@ Line 644: / Line 683: @@
 |}
 RT: '''<u>R</u>'''adiation '''<u>T</u>'''herapy
 ===Regimen {{#subobject:6a18dc|Variant=1}}===
 {| border="1" style="text-align:center;" !align="left"
@@ Line 650: / Line 688: @@
 |[[Levels_of_Evidence#Evidence|'''Evidence''']]
 |'''Comparator'''
+|[[Levels_of_Evidence#Efficacy|'''Efficacy''']]
 |-
 |[http://www.nejm.org/doi/full/10.1056/NEJMoa1106106 James et al. 2012 (BC2001)]
 |style="background-color:#00CD00"|Phase III
 |[[Bladder_cancer#Radiation_therapy_2|Radiation therapy]]
+|style="background-color:#00CD00"|Seems to have superior locoregional DFS
 |-
 |}
@@ Line 664: / Line 704: @@
 ===References===
-# 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. [http://www.nejm.org/doi/full/10.1056/NEJMoa1106106 link to original article] [http://www.nejm.org/doi/suppl/10.1056/NEJMoa1106106/suppl_file/nejmoa1106106_appendix.pdf link to supplementary index] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/22512481 PubMed]
+# 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. [http://www.nejm.org/doi/full/10.1056/NEJMoa1106106 link to original article] [http://www.nejm.org/doi/suppl/10.1056/NEJMoa1106106/suppl_file/nejmoa1106106_appendix.pdf link to supplementary index] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/22512481 PubMed]
 ==Paclitaxel & RT {{#subobject:89c0ea|Regimen=1}}==
@@ Line 677: / Line 717: @@
 |-
 |[http://www.goldjournal.net/article/S0090-4295%2812%2900867-9/abstract Zapatero et al. 2012]
-|<span
+|style="background-color:#ff0000"|Non-randomized, <20 pts
-style="background:#ff0000;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Non-randomized, <20 pts</span>
 |-
 |}''Patients who had "mild renal insufficiency" received paclitaxel instead of cisplatin and had T2 to T4 N0 M0 disease.''
@@ Line 689: / Line 724: @@
 *[[Paclitaxel (Taxol)]] 50 mg/m<sup>2</sup> IV once per week, given 6 hours before radiation therapy
 *Concurrent radiation therapy according to one of the following:
-**Accelerated hyperfractionated RT (AHFRT) 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.
+**Accelerated hyperfractionated RT (AHFRT) 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.
 **Normo-fractionated 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.
-'''3 weeks after finishing radiation and chemotherapy, patients underwent restaging TURBT.'''  Patient with complete regression (R0) continued to consolidation therapy.  Nonresponders proceeded to cystectomy.
+'''3 weeks after finishing radiation and chemotherapy, patients underwent restaging TURBT.''' Patient with complete regression (R0) continued to consolidation therapy. Nonresponders proceeded to cystectomy.
 ====Consolidation therapy====
 *[[Paclitaxel (Taxol)]] 50 mg/m<sup>2</sup> IV once per week, given 6 hours before radiation therapy
 *Concurrent radiation therapy according to one of the following:
-**Accelerated hyperfractionated RT (AHFRT), 1.5 Gy fractions twice per day x 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.
+**Accelerated hyperfractionated RT (AHFRT), 1.5 Gy fractions twice per day x 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.
 **Normo-fractionated 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.
 ===References===
-# Zapatero A, Martin 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. [http://www.goldjournal.net/article/S0090-4295%2812%2900867-9/abstract link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/22999456 PubMed]
+# Zapatero A, Martin 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. [http://www.goldjournal.net/article/S0090-4295%2812%2900867-9/abstract link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/22999456 PubMed]
 ==Radiation therapy {{#subobject:1103c0|Regimen=1}}==
@@ Line 714: / Line 749: @@
 |[[Levels_of_Evidence#Evidence|'''Evidence''']]
 |'''Comparator'''
+|[[Levels_of_Evidence#Efficacy|'''Efficacy''']]
 |-
 |[http://www.nejm.org/doi/full/10.1056/NEJMoa1106106 James et al. 2012 (BC2001)]
 |style="background-color:#00CD00"|Phase III
 |[[Bladder_cancer#Fluorouracil.2C_Mitomycin.2C_RT|Fluorouracil, Mitomycin, RT]]
+|style="background-color:#ff0000"|Seems to have inferior locoregional DFS
 |-
 |}
-''Inferior to chemoradiation with fluorouracil, mitomycin, RT; included for reference purposes only.''
+''Included here for reference purposes only.''
 ===References===
-# 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. [http://www.nejm.org/doi/full/10.1056/NEJMoa1106106 link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/22512481 PubMed]
+# 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. [http://www.nejm.org/doi/full/10.1056/NEJMoa1106106 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/22512481 PubMed]
 =Adjuvant chemotherapy=
-==Observation {{#subobject:33b2f2|Regimen=1}}==
+==Observation==
 {| class="wikitable" style="float:right; margin-left: 5px;"
 |-
@@ Line 733: / Line 770: @@
 |}
-===Regimen {{#subobject:c5b59e|Variant=1}}===
+===Regimen===
 {| border="1" style="text-align:center;" !align="left"
 |'''Study'''
 |[[Levels_of_Evidence#Evidence|'''Evidence''']]
 |'''Comparator'''
+|[[Levels_of_Evidence#Efficacy|'''Efficacy''']]
 |-
 |[http://meetinglibrary.asco.org/content/51401-74 Paz-Ares et al 2010 (SOGUG 99/01)]
 |style="background-color:#00CD00"|Phase III
 |[[Bladder_cancer#PGC|PGC]]
+|style="background-color:#ff0000"|Inferior OS
 |-
 |}
 ''Patients in SOGUG 99/01 had pT3-4 and/or pN positive disease with adequate renal function (CrCl > 50 ml/min). This arm underwent cystectomy and no further treatment. The study prematurely closed due to poor recruitment and lacks adequate power to make firm conclusions.''
@@ Line 755: / Line 793: @@
 |[[#top|back to top]]
 |}
 PGC: '''<u>P</u>'''aclitaxel, '''<u>G</u>'''emcitabine, '''<u>C</u>'''isplatin
 ===Regimen {{#subobject:ad1bc8|Variant=1}}===
 {| border="1" style="text-align:center;" !align="left"
@@ Line 763: / Line 799: @@
 |[[Levels_of_Evidence#Evidence|'''Evidence''']]
 |'''Comparator'''
+|[[Levels_of_Evidence#Efficacy|'''Efficacy''']]
 |-
 |[http://meetinglibrary.asco.org/content/51401-74 Paz-Ares et al 2010 (SOGUG 99/01)]
 |style="background-color:#00CD00"|Phase III
 |[[Bladder_cancer#Observation|Observation]]
+|style="background-color:#00CD00"|Superior OS
 |-
 |}
@@ Line 807: / Line 845: @@
 *Accelerated concurrent radiation therapy, 1.8 Gy fractions x 12 fractions to the bladder tumor, bladder, and regional lymph nodes; 4 to 6 hours later, a 1.6 Gy fraction x 12 fractions is given to the tumor plus a 2 cm margin. Radiation therapy given 5 days per week; treatment on days 1 to 5, 8 to 12, 15 to 16. Total induction dose to bladder tumor: 40.8 Gy; total induction dose to regional lymph nodes: 21.6 Gy.
-'''16-day course.'''  3 weeks after chemotherapy & radiation, patients were restaged with cystoscopy, tumor site biopsy, and urine cytology.  Patients with complete response proceeded to consolidation therapy.  Patients who did not achieve complete response proceeded to cystectomy.
+'''16-day course.''' 3 weeks after chemotherapy & radiation, patients were restaged with cystoscopy, tumor site biopsy, and urine cytology. Patients with complete response proceeded to consolidation therapy. Patients who did not achieve complete response proceeded to cystectomy.
 ====Consolidation therapy====
@@ Line 817: / Line 855: @@
 ====Adjuvant MCV====
-''Begins 8 weeks after initial therapy.  Only 45% of patients in Hagan, et al. 2003 (RTOG 97-06) were able to complete 3 cycles of MCV''
+''Begins 8 weeks after initial therapy. Only 45% of patients in Hagan, et al. 2003 (RTOG 97-06) were able to complete 3 cycles of MCV''
 *[[Methotrexate (MTX)]] 30 mg/m<sup>2</sup> IV once per day on days 1, 15, 22
 *[[Cisplatin (Platinol)]] 25 mg/m<sup>2</sup> IV once per day on days 2 to 4
@@ Line 825: / Line 863: @@
 ===References===
-# 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. [http://www.redjournal.org/article/S0360-3016%2803%2900718-1/abstract link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/14529770 PubMed]
+# 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. [http://www.redjournal.org/article/S0360-3016%2803%2900718-1/abstract link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/14529770 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. [http://jco.ascopubs.org/content/27/25/4055.long link to original article] [http://www.ncbi.nlm.nih.gov/pubmed/19636019 PubMed] content property of [http://hemonc.org HemOnc.org]
+## '''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. [http://jco.ascopubs.org/content/27/25/4055.long link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/19636019 PubMed] content property of [http://hemonc.org HemOnc.org]
-## '''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 Nov 3. [http://jco.ascopubs.org/content/32/34/3801.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/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 Nov 3. [http://jco.ascopubs.org/content/32/34/3801.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/25366678 PubMed]
 ==Cisplatin, Paclitaxel, RT --> Cisplatin & Gemcitabine {{#subobject:803f28|Regimen=1}}==
@@ Line 847: / Line 885: @@
 *[[Cisplatin (Platinol)]] 20 mg/m<sup>2</sup> IV once per day on days 1, 2, 8, 9, 15, 16
 *[[Paclitaxel (Taxol)]] 50 mg/m<sup>2</sup> IV once per day on days 1, 8, 15
-*Concurrent radiation therapy, with BID RT on days 1 to 5, 8 to 12, 15 to 17; 4 to 6 hours between radiation sessions.  Kaufman et al. 2009 (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 radiation as follows:
+*Concurrent radiation therapy, with BID RT on days 1 to 5, 8 to 12, 15 to 17; 4 to 6 hours between radiation sessions. Kaufman et al. 2009 (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 radiation as follows:
 **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
@@ Line 853: / Line 891: @@
 **Total doses: pelvis: 20.8 Gy; whole bladder: 28.3 Gy; bladder tumor volume 40.3 Gy.
-'''3-week course'''. On week 7, over 3 weeks after induction therapy, patients under reevaluation with exam under anesthesia, cystoscopy with tumor site biopsy, and urine cytology.  Patients with less than stage T1 disease proceeded to consolidation therapy.  Patients with at least Stage T1 disease proceeded to radical cystectomy, followed by adjuvant chemotherapy.  '''Note:''' The abstract of Kaufman, et al. 2009 (RTOG 99-06) 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 T1 disease.
+'''3-week course'''. On week 7, over 3 weeks after induction therapy, patients under reevaluation with exam under anesthesia, cystoscopy with tumor site biopsy, and urine cytology. Patients with less than stage T1 disease proceeded to consolidation therapy. Patients with at least Stage T1 disease proceeded to radical cystectomy, followed by adjuvant chemotherapy. '''Note:''' The abstract of Kaufman, et al. 2009 (RTOG 99-06) 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 T1 disease.
 ====Consolidation therapy====
@@ Line 859: / Line 897: @@
 *[[Cisplatin (Platinol)]] 20 mg/m<sup>2</sup> IV once per day on days 1, 2, 8, 9
 *[[Paclitaxel (Taxol)]] 50 mg/m<sup>2</sup> IV once per day on days 1 & 8
-*Concurrent radiation therapy, 1.5 Gy fractions x 16 fractions, given twice per day (4 to 6 hour interval between treatments) on days 1 to 5, 8 to 10.  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.
+*Concurrent radiation therapy, 1.5 Gy fractions x 16 fractions, given twice per day (4 to 6 hour interval between treatments) on days 1 to 5, 8 to 10. 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'''
@@ Line 871: / Line 909: @@
 ===References===
-# 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. [http://www.goldjournal.net/article/S0090-4295%2808%2901658-0/abstract link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/19100600 PubMed]
+# 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. [http://www.goldjournal.net/article/S0090-4295%2808%2901658-0/abstract link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/19100600 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 Nov 3. [http://jco.ascopubs.org/content/32/34/3801.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/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 Nov 3. [http://jco.ascopubs.org/content/32/34/3801.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/25366678 PubMed]
 ==Cisplatin, Paclitaxel, RT --> Cisplatin, Gemcitabine, Paclitaxel {{#subobject:919779|Regimen=1}}==
@@ Line 883: / Line 921: @@
 |'''Study'''
 |[[Levels_of_Evidence#Evidence|'''Evidence''']]
-|Comparator
+|'''Comparator'''
+|[[Levels_of_Evidence#Efficacy|'''Efficacy''']]
 |-
-|[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3955198/ Mitin et al. 2103 (RTOG 02-33)]
+|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3955198/ Mitin et al. 2013 (RTOG 02-33)]
-|<span
+|style="background-color:#00cd00"|Randomized Phase II
-style="background:#00cd00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Randomized Phase II</span>
 |Fluorouracil, Cisplatin, RT --> Cisplatin, Gemcitabine, Paclitaxel
+|style="background-color:#d3d3d3"|Not reported
 |-
 |}
@@ Line 904: / Line 939: @@
 **Total doses: pelvis: 20.8 Gy; whole bladder: 28.3 Gy; bladder tumor volume 40.3 Gy.
-'''3-week course'''. On week 7, patients under reevaluation for response.  Patients with less than stage T1 disease proceeded to consolidation therapy. Patients with at least stage T1 disease proceeded to radical cystectomy on week 9, followed by adjuvant chemotherapy.
+'''3-week course'''. On week 7, patients under reevaluation for response. Patients with less than stage T1 disease proceeded to consolidation therapy. Patients with at least stage T1 disease proceeded to radical cystectomy on week 9, followed by adjuvant chemotherapy.
 ====Consolidation therapy====
@@ Line 910: / Line 945: @@
 *[[Cisplatin (Platinol)]] 15 mg/m<sup>2</sup> IV once per day on days 1, 2, 8, 9
 *[[Paclitaxel (Taxol)]] 50 mg/m<sup>2</sup> IV once per day on days 1 & 8
-*Concurrent radiation therapy, 1.5 Gy fractions x 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.
+*Concurrent radiation therapy, 1.5 Gy fractions x 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'''
@@ Line 923: / Line 958: @@
 ===References===
-# 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. [http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3955198/ link to PMC article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/23823157 PubMed]
+# 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. [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3955198/ link to PMC article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/23823157 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 Nov 3. [http://jco.ascopubs.org/content/32/34/3801.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/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 Nov 3. [http://jco.ascopubs.org/content/32/34/3801.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/25366678 PubMed]
 ==Fluorouracil, Cisplatin, RT --> Cisplatin, Gemcitabine, Paclitaxel {{#subobject:2a1042|Regimen=1}}==
@@ Line 935: / Line 970: @@
 |'''Study'''
 |[[Levels_of_Evidence#Evidence|'''Evidence''']]
-|Comparator
+|'''Comparator'''
+|[[Levels_of_Evidence#Efficacy|'''Efficacy''']]
 |-
-|[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3955198/ Mitin et al. 2103 (RTOG 02-33)]
+|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3955198/ Mitin et al. 2013 (RTOG 02-33)]
-|<span
+|style="background-color:#00cd00"|Randomized Phase II
-style="background:#00cd00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Randomized Phase II</span>
 |Cisplatin, Paclitaxel, RT --> Cisplatin, Gemcitabine, Paclitaxel
+|style="background-color:#d3d3d3"|Not reported
 |-
 |}
@@ Line 956: / Line 988: @@
 **Total doses: pelvis: 20.8 Gy; whole bladder: 28.3 Gy; bladder tumor volume 40.3 Gy.
-'''3-week course'''. On week 7, patients under reevaluation for response.  Patients with less than stage T1 disease proceeded to consolidation therapy. Patients with at least stage T1 disease proceeded to radical cystectomy on week 9, followed by adjuvant chemotherapy.
+'''3-week course'''. On week 7, patients under reevaluation for response. Patients with less than stage T1 disease proceeded to consolidation therapy. Patients with at least stage T1 disease proceeded to radical cystectomy on week 9, followed by adjuvant chemotherapy.
 ====Consolidation therapy====
@@ Line 962: / Line 994: @@
 *[[Fluorouracil (5-FU)]] 400 mg/m<sup>2</sup> IV once per day on days 1 to 3, 8 to 10
 *[[Cisplatin (Platinol)]] 15 mg/m<sup>2</sup> IV once per day on days 1, 2, 8, 9
-*Concurrent radiation therapy, 1.5 Gy fractions x 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.
+*Concurrent radiation therapy, 1.5 Gy fractions x 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'''
@@ Line 975: / Line 1,007: @@
 ===References===
-# 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. [http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3955198/ link to PMC article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/23823157 PubMed]
+# 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. [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3955198/ link to PMC article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/23823157 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 Nov 3. [http://jco.ascopubs.org/content/32/34/3801.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/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 Nov 3. [http://jco.ascopubs.org/content/32/34/3801.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/25366678 PubMed]
 =Locally advanced or metastatic disease=
@@ Line 1,002: / Line 1,034: @@
 ===References===
-# Rosenberg JE, Hoffman-Censits J, Powles T, van der Heijden MS, Balar AV, Necchi A, Dawson N, O'Donnell PH, Balmanoukian A, Loriot Y, Srinivas S, Retz MM, Grivas P, Joseph RW, Galsky MD, Fleming MT, Petrylak DP, Perez-Gracia JL, Burris HA, Castellano D, Canil C, Bellmunt J, Bajorin D, Nickles D, Bourgon R, Frampton GM, Cui N, Mariathasan S, Abidoye O, Fine GD, Dreicer R. Atezolizumab in patients with locally advanced and metastatic urothelial carcinoma who have progressed following treatment with platinum-based chemotherapy: a single-arm, multicentre, phase 2 trial. Lancet. 2016 Mar 4. [Epub ahead of print] [http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(16)00561-4/fulltext link to original article] '''contains protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/26952546 PubMed]
+# Rosenberg JE, Hoffman-Censits J, Powles T, van der Heijden MS, Balar AV, Necchi A, Dawson N, O'Donnell PH, Balmanoukian A, Loriot Y, Srinivas S, Retz MM, Grivas P, Joseph RW, Galsky MD, Fleming MT, Petrylak DP, Perez-Gracia JL, Burris HA, Castellano D, Canil C, Bellmunt J, Bajorin D, Nickles D, Bourgon R, Frampton GM, Cui N, Mariathasan S, Abidoye O, Fine GD, Dreicer R. Atezolizumab in patients with locally advanced and metastatic urothelial carcinoma who have progressed following treatment with platinum-based chemotherapy: a single-arm, multicentre, phase 2 trial. Lancet. 2016 Mar 4. [Epub ahead of print] [http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(16)00561-4/fulltext link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/26952546 PubMed]
 ==Carboplatin & Gemcitabine (GC) {{#subobject:8855e5|Regimen=1}}==
@@ Line 1,010: / Line 1,042: @@
 |}
 GC: '''<u>G</u>'''emcitabine, '''<u>C</u>'''arboplatin
 ===Regimen {{#subobject:5f00b7|Variant=1}}===
 {| border="1" style="text-align:center;" !align="left"
@@ Line 1,018: / Line 1,049: @@
 |'''Comparator'''
 |Comparator [[Overall response rate|'''ORR''']]
+|[[Levels_of_Evidence#Efficacy|'''Efficacy''']]
 |Pt Population
 |-
-|[http://linkinghub.elsevier.com/retrieve/pii/S0302-2838(06)01589-2 Dogliotti et al. 2006]
+|[http://www.sciencedirect.com/science/article/pii/S0302283806015892 Dogliotti et al. 2006]
 |style="background-color:#00CD00"|Randomized Phase II
 |Intention to treat: 40% (95% CI NR)<br>Evaluable patients only: 56%<br>(95% CI: 40–72)
 |[[Bladder_cancer#Cisplatin_.26_Gemcitabine_.28GC.2FGP.29|Cisplatin & Gemcitabine]]
 |Intention to treat: 49% (95% CI NR)<br>Evaluable patients only: 66%<br>(95% CI: 49–80)
+|style="background-color:#eeee00"|Seems not superior
 |Chemo-naive
 |-
@@ Line 1,035: / Line 1,068: @@
 ===References===
-# Dogliotti L, Cartenì G, Siena S, Bertetto O, Martoni A, Bono A, Amadori D, Onat H, Marini L. Gemcitabine plus cisplatin versus gemcitabine plus carboplatin as first-line chemotherapy in advanced transitional cell carcinoma of the urothelium: results of a randomized phase 2 trial. Eur Urol. 2007 Jul;52(1):134-41. Epub 2006 Dec 26. [http://linkinghub.elsevier.com/retrieve/pii/S0302-2838(06)01589-2 link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/17207911 PubMed]
+# Dogliotti L, Cartenì G, Siena S, Bertetto O, Martoni A, Bono A, Amadori D, Onat H, Marini L. Gemcitabine plus cisplatin versus gemcitabine plus carboplatin as first-line chemotherapy in advanced transitional cell carcinoma of the urothelium: results of a randomized phase 2 trial. Eur Urol. 2007 Jul;52(1):134-41. Epub 2006 Dec 26. [http://www.sciencedirect.com/science/article/pii/S0302283806015892 link to SD article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/17207911 PubMed]
 ==Carboplatin & Paclitaxel {{#subobject:b33fe7|Regimen=1}}==
@@ Line 1,063: / Line 1,096: @@
 ===References===
-# Vaughn DJ, Manola J, Dreicer R, See W, Levitt R, Wilding G. Phase II study of paclitaxel plus carboplatin in patients with advanced carcinoma of the urothelium and renal dysfunction (E2896): a trial of the Eastern Cooperative Oncology Group. Cancer. 2002 Sep 1;95(5):1022-7. [http://onlinelibrary.wiley.com/doi/10.1002/cncr.10782/full link to original article] '''contains protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/12209686 PubMed]
+# Vaughn DJ, Manola J, Dreicer R, See W, Levitt R, Wilding G. Phase II study of paclitaxel plus carboplatin in patients with advanced carcinoma of the urothelium and renal dysfunction (E2896): a trial of the Eastern Cooperative Oncology Group. Cancer. 2002 Sep 1;95(5):1022-7. [http://onlinelibrary.wiley.com/doi/10.1002/cncr.10782/full link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/12209686 PubMed]
 ==CISCA {{#subobject:b60f2a|Regimen=1}}==
@@ Line 1,079: / Line 1,112: @@
 |'''Comparator'''
 |Comparator [[Overall response rate|'''ORR''']]
+|[[Levels_of_Evidence#Efficacy|'''Efficacy''']]
 |Pt Population
 |-
@@ Line 1,086: / Line 1,120: @@
 |[[Bladder_cancer#MVAC_2|MVAC]]
 |'''65%''' (95% CI 52-77%)
+|style="background-color:#ff0000"|Inferior OS
 |Chemo-naive
 |-
@@ Line 1,100: / Line 1,135: @@
 ===References===
-# Logothetis CJ, Dexeus FH, Finn L, Sella A, Amato RJ, Ayala AG, Kilbourn RG. A prospective randomized trial comparing MVAC and CISCA chemotherapy for patients with metastatic urothelial tumors. J Clin Oncol. 1990 Jun;8(6):1050-5. [http://jco.ascopubs.org/content/8/6/1050.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/2189954 PubMed]
+# Logothetis CJ, Dexeus FH, Finn L, Sella A, Amato RJ, Ayala AG, Kilbourn RG. A prospective randomized trial comparing MVAC and CISCA chemotherapy for patients with metastatic urothelial tumors. J Clin Oncol. 1990 Jun;8(6):1050-5. [http://jco.ascopubs.org/content/8/6/1050.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/2189954 PubMed]
 ==Cisplatin & Gemcitabine (GC/GP) {{#subobject:5cbd83|Regimen=1}}==
@@ Line 1,115: / Line 1,150: @@
 |[[Levels_of_Evidence#Evidence|'''Evidence''']]
 |'''Comparator'''
+|[[Levels_of_Evidence#Efficacy|'''Efficacy''']]
 |-
 |[http://jco.ascopubs.org/content/18/17/3068.long von der Maase et al. 2000]
 |style="background-color:#00CD00"|Phase III
 |[[Bladder_cancer#MVAC_2|MVAC]]
+|style="background-color:#eeee00"|Seems not superior
 |-
 |[http://annonc.oxfordjournals.org/content/13/7/1080.long Soto Parra et al. 2002]
-|style="background-color:#00CD00"|Randomized Phase II
+|style="background-color:#ff0000"|Randomized Phase II, <20 pts in this subgroup
 |Cisplatin & Gemcitabine, 3-week schedule, gemcitabine at 1000 mg/m<sup>2</sup>
+|style="background-color:#d3d3d3"|Not reported
 |-
-|[http://jco.ascopubs.org/content/early/2012/02/27/JCO.2011.38.6979.long Bellmunt et al. 2012 (EORTC 30987)]
+|[http://ascopubs.org/doi/full/10.1200/JCO.2011.38.6979 Bellmunt et al. 2012 (EORTC 30987)]
 |style="background-color:#00CD00"|Phase III
 |[[Bladder_cancer#Cisplatin.2C_Gemcitabine.2C_Paclitaxel_.28PCG.29|PCG]]
+|style="background-color:#ff0000"|Might have inferior OS
 |-
 |}
@@ Line 1,142: / Line 1,181: @@
 '''28-day cycle for up to 6 cycles, progression of disease, unacceptable toxicity, or physician discretion based on patient's best interests'''
-===Regimen #2, 3-week schedule, gemcitabine at 1250 mg/m<sup>2</sup>  {{#subobject:44c03b|Variant=1}}===
+===Regimen #2, 3-week schedule, gemcitabine at 1250 mg/m<sup>2</sup> {{#subobject:44c03b|Variant=1}}===
 {| border="1" style="text-align:center;" !align="left"
 |'''Study'''
@@ Line 1,149: / Line 1,188: @@
 |'''Comparator'''
 |Comparator [[Overall response rate|'''ORR''']]
+|[[Levels_of_Evidence#Efficacy|'''Efficacy''']]
 |Pt Population
 |-
@@ Line 1,156: / Line 1,196: @@
 |[[Bladder_cancer#Carboplatin_.26_Gemcitabine_.28GC.29|Carboplatin & Gemcitabine]]
 |Intention to treat: 40% (95% CI NR)<br>Evaluable patients only: 56%<br>(95% CI: 40–72)
+|style="background-color:#eeee00"|Seems not superior
 |Chemo-naive
 |-
@@ Line 1,169: / Line 1,210: @@
 |'''Study'''
 |[[Levels_of_Evidence#Evidence|'''Evidence''']]
-|[[Overall response rate|'''ORR''']]
 |'''Comparator'''
-|Comparator [[Overall response rate|'''ORR''']]
+|[[Levels_of_Evidence#Efficacy|'''Efficacy''']]
 |Pt Population
 |-
 |[http://annonc.oxfordjournals.org/content/13/7/1080.long Soto Parra et al. 2002]
-|style="background-color:#00CD00"|Randomized Phase II
+|style="background-color:#ff0000"|Randomized Phase II, <20 pts in this subgroup
-|42% (95% CI NR)
 |Cisplatin & Gemcitabine, 4-week schedule
-|38% (95% CI NR)
+|style="background-color:#d3d3d3"|Not reported
 |Chemo-naive
 |-
@@ Line 1,193: / Line 1,232: @@
 ===References===
-# von der Maase H, Hansen SW, Roberts JT, Dogliotti L, Oliver T, Moore MJ, Bodrogi I, Albers P, Knuth A, Lippert CM, Kerbrat P, Sanchez Rovira P, Wersall P, Cleall SP, Roychowdhury DF, Tomlin I, Visseren-Grul CM, Conte PF. Gemcitabine and cisplatin versus methotrexate, vinblastine, doxorubicin, and cisplatin in advanced or metastatic bladder cancer: results of a large, randomized, multinational, multicenter, phase III study. J Clin Oncol. 2000 Sep;18(17):3068-77. [http://jco.ascopubs.org/content/18/17/3068.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/11001674 PubMed]
+# von der Maase H, Hansen SW, Roberts JT, Dogliotti L, Oliver T, Moore MJ, Bodrogi I, Albers P, Knuth A, Lippert CM, Kerbrat P, Sanchez Rovira P, Wersall P, Cleall SP, Roychowdhury DF, Tomlin I, Visseren-Grul CM, Conte PF. Gemcitabine and cisplatin versus methotrexate, vinblastine, doxorubicin, and cisplatin in advanced or metastatic bladder cancer: results of a large, randomized, multinational, multicenter, phase III study. J Clin Oncol. 2000 Sep;18(17):3068-77. [http://jco.ascopubs.org/content/18/17/3068.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/11001674 PubMed]
-# Soto Parra H, Cavina R, Latteri F, Sala A, Dambrosio M, Antonelli G, Morenghi E, Alloisio M, Ravasi G, Santoro A. Three-week versus four-week schedule of cisplatin and gemcitabine: results of a randomized phase II study. Ann Oncol. 2002 Jul;13(7):1080-6. [http://annonc.oxfordjournals.org/content/13/7/1080.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/12176787 PubMed]
+# Soto Parra H, Cavina R, Latteri F, Sala A, Dambrosio M, Antonelli G, Morenghi E, Alloisio M, Ravasi G, Santoro A. Three-week versus four-week schedule of cisplatin and gemcitabine: results of a randomized phase II study. Ann Oncol. 2002 Jul;13(7):1080-6. [http://annonc.oxfordjournals.org/content/13/7/1080.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/12176787 PubMed]
-# Dogliotti L, Cartenì G, Siena S, Bertetto O, Martoni A, Bono A, Amadori D, Onat H, Marini L. Gemcitabine plus cisplatin versus gemcitabine plus carboplatin as first-line chemotherapy in advanced transitional cell carcinoma of the urothelium: results of a randomized phase 2 trial. Eur Urol. 2007 Jul;52(1):134-41. Epub 2006 Dec 26. [http://www.sciencedirect.com/science/article/pii/S0302283806015892 link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/17207911 PubMed]
+# Dogliotti L, Cartenì G, Siena S, Bertetto O, Martoni A, Bono A, Amadori D, Onat H, Marini L. Gemcitabine plus cisplatin versus gemcitabine plus carboplatin as first-line chemotherapy in advanced transitional cell carcinoma of the urothelium: results of a randomized phase 2 trial. Eur Urol. 2007 Jul;52(1):134-41. Epub 2006 Dec 26. [http://www.sciencedirect.com/science/article/pii/S0302283806015892 link to SD article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/17207911 PubMed]
-# Bellmunt J, von der Maase H, Mead GM, Skoneczna I, De Santis M, Daugaard G, Boehle A, Chevreau C, Paz-Ares L, Laufman LR, Winquist E, Raghavan D, Marreaud S, Collette S, Sylvester R, de Wit R. Randomized Phase III Study Comparing Paclitaxel/Cisplatin/ Gemcitabine and Gemcitabine/Cisplatin in Patients With Locally Advanced or Metastatic Urothelial Cancer Without Prior Systemic Therapy: EORTC Intergroup Study 30987. J Clin Oncol. 2012 Apr 1;30(10):1107-13. Epub 2012 Feb 27. [http://jco.ascopubs.org/content/early/2012/02/27/JCO.2011.38.6979.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/22370319 PubMed]
+# Bellmunt J, von der Maase H, Mead GM, Skoneczna I, De Santis M, Daugaard G, Boehle A, Chevreau C, Paz-Ares L, Laufman LR, Winquist E, Raghavan D, Marreaud S, Collette S, Sylvester R, de Wit R. Randomized Phase III Study Comparing Paclitaxel/Cisplatin/ Gemcitabine and Gemcitabine/Cisplatin in Patients With Locally Advanced or Metastatic Urothelial Cancer Without Prior Systemic Therapy: EORTC Intergroup Study 30987. J Clin Oncol. 2012 Apr 1;30(10):1107-13. Epub 2012 Feb 27. [http://ascopubs.org/doi/full/10.1200/JCO.2011.38.6979 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/22370319 PubMed]
 ==Cisplatin, Gemcitabine, Paclitaxel (PCG) {{#subobject:393eb6|Regimen=1}}==
@@ Line 1,212: / Line 1,251: @@
 |'''Comparator'''
 |Comparator [[Overall response rate|'''ORR''']]
+|[[Levels_of_Evidence#Efficacy|'''Efficacy''']]
 |Pt Population
 |-
-|[http://jco.ascopubs.org/content/early/2012/02/27/JCO.2011.38.6979.long Bellmunt et al. 2012 (EORTC 30987)]
+|[http://ascopubs.org/doi/full/10.1200/JCO.2011.38.6979 Bellmunt et al. 2012 (EORTC 30987)]
 |style="background-color:#00CD00"|Phase III
 |56% (95% CI NR)
 |[[Bladder_cancer#Cisplatin_.26_Gemcitabine_.28GC.2FGP.29|Cisplatin & Gemcitabine]]
 |44% (95% CI NR)
+|style="background-color:#00CD00"|Might have superior OS
 |Chemo-naive
 |-
@@ Line 1,230: / Line 1,271: @@
 ===References===
-# Bellmunt J, von der Maase H, Mead GM, Skoneczna I, De Santis M, Daugaard G, Boehle A, Chevreau C, Paz-Ares L, Laufman LR, Winquist E, Raghavan D, Marreaud S, Collette S, Sylvester R, de Wit R. Randomized Phase III Study Comparing Paclitaxel/Cisplatin/ Gemcitabine and Gemcitabine/Cisplatin in Patients With Locally Advanced or Metastatic Urothelial Cancer Without Prior Systemic Therapy: EORTC Intergroup Study 30987. J Clin Oncol. 2012 Apr 1;30(10):1107-13. Epub 2012 Feb 27. [http://jco.ascopubs.org/content/early/2012/02/27/JCO.2011.38.6979.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/22370319 PubMed]
+# Bellmunt J, von der Maase H, Mead GM, Skoneczna I, De Santis M, Daugaard G, Boehle A, Chevreau C, Paz-Ares L, Laufman LR, Winquist E, Raghavan D, Marreaud S, Collette S, Sylvester R, de Wit R. Randomized Phase III Study Comparing Paclitaxel/Cisplatin/ Gemcitabine and Gemcitabine/Cisplatin in Patients With Locally Advanced or Metastatic Urothelial Cancer Without Prior Systemic Therapy: EORTC Intergroup Study 30987. J Clin Oncol. 2012 Apr 1;30(10):1107-13. Epub 2012 Feb 27. [http://ascopubs.org/doi/full/10.1200/JCO.2011.38.6979 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/22370319 PubMed]
-==Docetaxel{{#subobject:385447|Regimen=1}}==
+==Docetaxel (Taxotere) {{#subobject:385447|Regimen=1}}==
 {| class="wikitable" style="float:right; margin-left: 5px;"
 |-
@@ Line 1,244: / Line 1,285: @@
 |'''Comparator'''
 |Comparator [[Overall response rate|'''ORR''']]
+|[[Levels_of_Evidence#Efficacy|'''Efficacy''']]
 |Pt Population
 |-
@@ Line 1,251: / Line 1,293: @@
 |Docetaxel & Vandetanib
 |7% (95% CI NR)
+|style="background-color:#eeee00"|Seems not superior
 |Mix of chemo-naive and treated
 |-
@@ Line 1,260: / Line 1,303: @@
 ===References===
-# McCaffrey JA, Hilton S, Mazumdar M, Sadan S, Kelly WK, Scher HI, Bajorin DF. Phase II trial of docetaxel in patients with advanced or metastatic transitional-cell carcinoma. J Clin Oncol. 1997 May;15(5):1853-7. [http://jco.ascopubs.org/content/15/5/1853.full.pdf+html link to original article] [http://www.ncbi.nlm.nih.gov/pubmed/9164195 PubMed]
+# McCaffrey JA, Hilton S, Mazumdar M, Sadan S, Kelly WK, Scher HI, Bajorin DF. Phase II trial of docetaxel in patients with advanced or metastatic transitional-cell carcinoma. J Clin Oncol. 1997 May;15(5):1853-7. [http://jco.ascopubs.org/content/15/5/1853.full.pdf+html link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/9164195 PubMed]
-# Choueiri TK, Ross RW, Jacobus S, Vaishampayan U, Yu EY, Quinn DI, Hahn NM, Hutson TE, Sonpavde G, Morrissey SC, Buckle GC, Kim WY, Petrylak DP, Ryan CW, Eisenberger MA, Mortazavi A, Bubley GJ, Taplin ME, Rosenberg JE, Kantoff PW. Double-blind, randomized trial of docetaxel plus vandetanib versus docetaxel plus placebo in platinum-pretreated metastatic urothelial cancer. J Clin Oncol. 2012 Feb 10;30(5):507-12. [http://jco.ascopubs.org/content/30/5/507.long link to original article] [http://www.ncbi.nlm.nih.gov/pubmed/22184381 PubMed]
+# Choueiri TK, Ross RW, Jacobus S, Vaishampayan U, Yu EY, Quinn DI, Hahn NM, Hutson TE, Sonpavde G, Morrissey SC, Buckle GC, Kim WY, Petrylak DP, Ryan CW, Eisenberger MA, Mortazavi A, Bubley GJ, Taplin ME, Rosenberg JE, Kantoff PW. Double-blind, randomized trial of docetaxel plus vandetanib versus docetaxel plus placebo in platinum-pretreated metastatic urothelial cancer. J Clin Oncol. 2012 Feb 10;30(5):507-12. [http://jco.ascopubs.org/content/30/5/507.long link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/22184381 PubMed]
 ==Gemcitabine & Paclitaxel {{#subobject:385447|Regimen=1}}==
@@ Line 1,289: / Line 1,332: @@
 ===References===
-# Meluch AA, Greco FA, Burris HA 3rd, O'Rourke T, Ortega G, Steis RG, Morrissey LH, Johnson V, Hainsworth JD. Paclitaxel and gemcitabine chemotherapy for advanced transitional-cell carcinoma of the urothelial tract: a phase II trial of the Minnie pearl cancer research network. J Clin Oncol. 2001 Jun 15;19(12):3018-24. [http://jco.ascopubs.org/content/19/12/3018.long link to original article] [http://www.ncbi.nlm.nih.gov/pubmed/11408496 PubMed]
+# Meluch AA, Greco FA, Burris HA 3rd, O'Rourke T, Ortega G, Steis RG, Morrissey LH, Johnson V, Hainsworth JD. Paclitaxel and gemcitabine chemotherapy for advanced transitional-cell carcinoma of the urothelial tract: a phase II trial of the Minnie pearl cancer research network. J Clin Oncol. 2001 Jun 15;19(12):3018-24. [http://jco.ascopubs.org/content/19/12/3018.long link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/11408496 PubMed]
 ==MVAC {{#subobject:d2ea09|Regimen=1}}==
@@ Line 1,305: / Line 1,348: @@
 |'''Comparator'''
 |Comparator [[Overall response rate|'''ORR''']]
+|[[Levels_of_Evidence#Efficacy|'''Efficacy''']]
 |Pt Population
 |-
@@ Line 1,312: / Line 1,356: @@
 |Standard MVAC
 |50% (95% CI 42-59%)
+|style="background-color:#00CD00"|Seems to have superior PFS
 |Chemo-naive
 |-
@@ Line 1,322: / Line 1,367: @@
 ====Supportive medications====
 *[[Filgrastim (Neupogen)|G-CSF]] 240 ug/m<sup>2</sup> SC once per day on days 4 to 10 (additional use up to a total of 14 consecutive days if needed), injected at alternating sites, discontinued if ANC >30 x 10<sup>9</sup>/L.
 **''In contrast to Sternberg et al. 2001, Sternberg et al. 2006 said G-CSF was given on days 3 to 7.''
@@ Line 1,334: / Line 1,379: @@
 |[[Levels_of_Evidence#Evidence|'''Evidence''']]
 |'''Comparator'''
+|[[Levels_of_Evidence#Efficacy|'''Efficacy''']]
 |-
 |[http://jco.ascopubs.org/content/8/6/1050.long Logothetis et al. 1990]
 |style="background-color:#00CD00"|Phase III
 |[[Bladder_cancer#CISCA|CISCA]]
+|style="background-color:#00CD00"|Superior OS
 |-
 |[http://jco.ascopubs.org/content/18/17/3068.long von der Maase et al. 2000]
 |style="background-color:#00CD00"|Phase III
 |[[Bladder_cancer#Cisplatin_.26_Gemcitabine_.28GC.2FGP.29|Cisplatin & Gemcitabine]]
+|style="background-color:#eeee00"|Seems not superior
 |-
 |[http://jco.ascopubs.org/content/19/10/2638.long Sternberg et al. 2001 (EORTC 30924)]
 |style="background-color:#00CD00"|Phase III
 |Dose-dense MVAC
+|style="background-color:#ff0000"|Seems to have inferior PFS
 |-
 |[http://www.nature.com/bjc/journal/v98/n1/full/6604113a.html Han et al. 2008]
-|<span
+|style="background-color:#eeee00"|Phase II
-style="background:#eeee00;
+|style="background-color:#d3d3d3"|
-padding:3px 6px 3px 6px;
+|style="background-color:#d3d3d3"|
-border-color:black;
-border-width:2px;
-border-style:solid;">Phase II</span>
-|
 |-
 |}
@@ Line 1,366: / Line 1,411: @@
 ===References===
-# Logothetis CJ, Dexeus FH, Finn L, Sella A, Amato RJ, Ayala AG, Kilbourn RG. A prospective randomized trial comparing MVAC and CISCA chemotherapy for patients with metastatic urothelial tumors. J Clin Oncol. 1990 Jun;8(6):1050-5. [http://jco.ascopubs.org/content/8/6/1050.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/2189954 PubMed]
+# Logothetis CJ, Dexeus FH, Finn L, Sella A, Amato RJ, Ayala AG, Kilbourn RG. A prospective randomized trial comparing MVAC and CISCA chemotherapy for patients with metastatic urothelial tumors. J Clin Oncol. 1990 Jun;8(6):1050-5. [http://jco.ascopubs.org/content/8/6/1050.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/2189954 PubMed]
-# von der Maase H, Hansen SW, Roberts JT, Dogliotti L, Oliver T, Moore MJ, Bodrogi I, Albers P, Knuth A, Lippert CM, Kerbrat P, Sanchez Rovira P, Wersall P, Cleall SP, Roychowdhury DF, Tomlin I, Visseren-Grul CM, Conte PF. Gemcitabine and cisplatin versus methotrexate, vinblastine, doxorubicin, and cisplatin in advanced or metastatic bladder cancer: results of a large, randomized, multinational, multicenter, phase III study. J Clin Oncol. 2000 Sep;18(17):3068-77. [http://jco.ascopubs.org/content/18/17/3068.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/11001674 PubMed]
+# von der Maase H, Hansen SW, Roberts JT, Dogliotti L, Oliver T, Moore MJ, Bodrogi I, Albers P, Knuth A, Lippert CM, Kerbrat P, Sanchez Rovira P, Wersall P, Cleall SP, Roychowdhury DF, Tomlin I, Visseren-Grul CM, Conte PF. Gemcitabine and cisplatin versus methotrexate, vinblastine, doxorubicin, and cisplatin in advanced or metastatic bladder cancer: results of a large, randomized, multinational, multicenter, phase III study. J Clin Oncol. 2000 Sep;18(17):3068-77. [http://jco.ascopubs.org/content/18/17/3068.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/11001674 PubMed]
-# Sternberg CN, de Mulder PH, Schornagel JH, Théodore C, Fossa SD, van Oosterom AT, Witjes F, Spina M, van Groeningen CJ, de Balincourt C, Collette L; European Organization for Research and Treatment of Cancer Genitourinary Tract Cancer Cooperative Group. Randomized phase III trial of high-dose-intensity methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC) chemotherapy and recombinant human granulocyte colony-stimulating factor versus classic MVAC in advanced urothelial tract tumors: European Organization for Research and Treatment of Cancer Protocol no. 30924. J Clin Oncol. 2001 May 15;19(10):2638-46. [http://jco.ascopubs.org/content/19/10/2638.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/11352955 PubMed]
+# Sternberg CN, de Mulder PH, Schornagel JH, Théodore C, Fossa SD, van Oosterom AT, Witjes F, Spina M, van Groeningen CJ, de Balincourt C, Collette L; European Organization for Research and Treatment of Cancer Genitourinary Tract Cancer Cooperative Group. Randomized phase III trial of high-dose-intensity methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC) chemotherapy and recombinant human granulocyte colony-stimulating factor versus classic MVAC in advanced urothelial tract tumors: European Organization for Research and Treatment of Cancer Protocol no. 30924. J Clin Oncol. 2001 May 15;19(10):2638-46. [http://jco.ascopubs.org/content/19/10/2638.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/11352955 PubMed]
-## '''Update:''' Sternberg CN, de Mulder P, Schornagel JH, Theodore C, Fossa SD, van Oosterom AT, Witjes JA, Spina M, van Groeningen CJ, Duclos B, Roberts JT, de Balincourt C, Collette L; EORTC Genito-Urinary Cancer Group. Seven year update of an EORTC phase III trial of high-dose intensity M-VAC chemotherapy and G-CSF versus classic M-VAC in advanced urothelial tract tumours. Eur J Cancer. 2006 Jan;42(1):50-4. Epub 2005 Dec 5. [http://www.sciencedirect.com/science/article/pii/S0959804905008749 link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/16330205 PubMed]
+## '''Update:''' Sternberg CN, de Mulder P, Schornagel JH, Theodore C, Fossa SD, van Oosterom AT, Witjes JA, Spina M, van Groeningen CJ, Duclos B, Roberts JT, de Balincourt C, Collette L; EORTC Genito-Urinary Cancer Group. Seven year update of an EORTC phase III trial of high-dose intensity M-VAC chemotherapy and G-CSF versus classic M-VAC in advanced urothelial tract tumours. Eur J Cancer. 2006 Jan;42(1):50-4. Epub 2005 Dec 5. [http://www.sciencedirect.com/science/article/pii/S0959804905008749 link to SD article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/16330205 PubMed]
-# Han KS, Joung JY, Kim TS, Jeong IG, Seo HK, Chung J, Lee KH. Methotrexate, vinblastine, doxorubicin and cisplatin combination regimen as salvage chemotherapy for patients with advanced or metastatic transitional cell carcinoma after failure of gemcitabine and cisplatin chemotherapy. Br J Cancer. 2008 Jan 15;98(1):86-90. Epub 2007 Dec 18. [http://www.nature.com/bjc/journal/v98/n1/full/6604113a.html link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/18087289 PubMed]
+# Han KS, Joung JY, Kim TS, Jeong IG, Seo HK, Chung J, Lee KH. Methotrexate, vinblastine, doxorubicin and cisplatin combination regimen as salvage chemotherapy for patients with advanced or metastatic transitional cell carcinoma after failure of gemcitabine and cisplatin chemotherapy. Br J Cancer. 2008 Jan 15;98(1):86-90. Epub 2007 Dec 18. [http://www.nature.com/bjc/journal/v98/n1/full/6604113a.html link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/18087289 PubMed]
 ==Nab-paclitaxel (Abraxane) {{#subobject:fec6dd|Regimen=1}}==
@@ Line 1,400: / Line 1,445: @@
 ===References===
-# Ko YJ, Canil CM, Mukherjee SD, Winquist E, Elser C, Eisen A, Reaume MN, Zhang L, Sridhar SS. Nanoparticle albumin-bound paclitaxel for second-line treatment of metastatic urothelial carcinoma: a single group, multicentre, phase 2 study. Lancet Oncol. 2013 Jul;14(8):769-76. [http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(13)70162-1/fulltext link to original article] '''contains protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/23706985 PubMed]
+# Ko YJ, Canil CM, Mukherjee SD, Winquist E, Elser C, Eisen A, Reaume MN, Zhang L, Sridhar SS. Nanoparticle albumin-bound paclitaxel for second-line treatment of metastatic urothelial carcinoma: a single group, multicentre, phase 2 study. Lancet Oncol. 2013 Jul;14(8):769-76. [http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(13)70162-1/fulltext link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/23706985 PubMed]
 ==Paclitaxel (Taxol) {{#subobject:fec6dd|Regimen=1}}==
@@ Line 1,427: / Line 1,472: @@
 ===References===
-# Vaughn DJ, Broome CM, Hussain M, Gutheil JC, Markowitz AB. Phase II trial of weekly paclitaxel in patients with previously treated advanced urothelial cancer. J Clin Oncol. 2002 Feb 15;20(4):937-40. [http://jco.ascopubs.org/content/20/4/937.long link to original article] '''contains protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/11844814 PubMed}
+# Vaughn DJ, Broome CM, Hussain M, Gutheil JC, Markowitz AB. Phase II trial of weekly paclitaxel in patients with previously treated advanced urothelial cancer. J Clin Oncol. 2002 Feb 15;20(4):937-40. [http://jco.ascopubs.org/content/20/4/937.long link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/11844814 PubMed}
 ==Pembrolizumab (Keytruda) {{#subobject:b0cd2a|Regimen=1}}==
@@ Line 1,440: / Line 1,485: @@
 |[[Levels_of_Evidence#Evidence|'''Evidence''']]
 |[[Overall response rate|'''ORR''']]
-|Comparator
+|'''Comparator'''
+|[[Levels_of_Evidence#Efficacy|'''Efficacy''']]
 |-
 |[http://meetinglibrary.asco.org/content/145993-156 Bellmunt et al. 2015 (KEYNOTE-045)]
 |style="background-color:#00CD00"|Phase III
 |24%
-|Paclitaxel 175 mg/m2 Q3W or<br>[[#Docetaxel|docetaxel]] or<br>vinflunine
+|Paclitaxel 175 mg/m2 Q3wk<br>[[#Docetaxel|docetaxel]]<br> Vinflunine
+|TBD
 |-
 |}
@@ Line 1,484: / Line 1,531: @@
 ===References===
-# Sweeney CJ, Roth BJ, Kabbinavar FF, Vaughn DJ, Arning M, Curiel RE, Obasaju CK, Wang Y, Nicol SJ, Kaufman DS. Phase II study of pemetrexed for second-line treatment of transitional cell cancer of the urothelium. J Clin Oncol. 2006 Jul 20;24(21):3451-7. [http://jco.ascopubs.org/content/24/21/3451.long link to original article] '''contains protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/16849761 PubMed]
+# Sweeney CJ, Roth BJ, Kabbinavar FF, Vaughn DJ, Arning M, Curiel RE, Obasaju CK, Wang Y, Nicol SJ, Kaufman DS. Phase II study of pemetrexed for second-line treatment of transitional cell cancer of the urothelium. J Clin Oncol. 2006 Jul 20;24(21):3451-7. [http://jco.ascopubs.org/content/24/21/3451.long link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/16849761 PubMed]
 =Links=
@@ Line 1,492: / Line 1,539: @@
 ''These are assays intended/being investigated as adjuncts to urine cytology and cystoscopy.''
 *[https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=347921 Cxbladder (uRNA-2)], a "urine based bladder cancer test (uRNA-2) which detects RNA markers in urine."
-*[http://www.scimedx.com/products/bladder_cancer/bladder_cancer.php ImmunoCyt™/uCyt+™], a cell-based detection assay which "uses fluorescent-labeled antibodies to 3 markers that are commonly found on malignant exfoliated urothelial cells."<ref>Greene KL, Berry A, Konety BR. Diagnostic Utility of the ImmunoCyt/uCyt+ Test in Bladder Cancer. Rev Urol. 2006 Fall;8(4):190-7. [http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1751037/ link to PMC article] [http://www.ncbi.nlm.nih.gov/pubmed/17192798 PubMed]</ref>
+*[http://www.scimedx.com/products/bladder_cancer/bladder_cancer.php ImmunoCyt™/uCyt+™], a cell-based detection assay which "uses fluorescent-labeled antibodies to 3 markers that are commonly found on malignant exfoliated urothelial cells."<ref>Greene KL, Berry A, Konety BR. Diagnostic Utility of the ImmunoCyt/uCyt+ Test in Bladder Cancer. Rev Urol. 2006 Fall;8(4):190-7. [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1751037/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/17192798 PubMed]</ref>
 *[http://www.abbottmolecular.com/us/products/oncology/fish/bladder-cancer-urovysion.html 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."

Difference between revisions of "Urothelial carcinoma"

Revision as of 14:32, 27 November 2016

Intravesical chemotherapy

Bacillus Calmette-Guerin (BCG)

Regimen #1, intravesical & percutaneous, with maintenance therapy

Induction therapy

Maintenance therapy

Regimen #2, intravesical & percutaneous, without maintenance therapy

Immunotherapy

Regimen #3, low-dose BCG

Induction therapy

Additional therapy

References

Doxorubicin (Adriamycin)

Regimen

Chemotherapy

References

Mitomycin (Mutamycin)

Regimen

Induction therapy

Additional therapy

References

Pirarubicin (THP)

Regimen

Chemotherapy

References

Placebo or observation

Regimen

References

Thiotepa (Thioplex)

Regimen

Chemotherapy

References

Neoadjuvant chemotherapy

Cisplatin & Gemcitabine (GC)

Regimen #1, single-dose cisplatin

Chemotherapy

Regimen #2, split-dose cisplatin

Chemotherapy

References

CMV; MCV

Regimen

Chemotherapy

Supportive medications

References

MVAC

Regimen

Chemotherapy

References

MVAC (dose-dense/accelerated)

Regimen #1, dose-dense MVAC

Chemotherapy

Supportive medications

Regimen #2, accelerated MVAC

Chemotherapy

Supportive medications

References

No neoadjuvant therapy

Regimen

References

Neoadjuvant chemotherapy -> RT

MCV -> RT

Regimen

Chemotherapy portion

Radiation therapy portion

References

Neoadjuvant chemotherapy -> concurrent chemotherapy & radiation therapy

MCV -> Cisplatin & RT

Regimen #1

Neoadjuvant chemotherapy

Neoadjuvant chemoradiotherapy

Consolidation therapy

Regimen #2

Neoadjuvant chemotherapy

Induction therapy

Consolidation therapy

References

Concurrent chemotherapy & radiation

Cisplatin & RT

Regimen #1