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Intravesical chemotherapy

Bacillus Calmette-Guerin (BCG)

Regimen #1, Lamm, et al. 2000 (intravesical & percutaneous, with maintenance therapy)

Induction therapy

Bacillus Calmette-Guerin (BCG) (Connaught strain) 81 mg in 50.5 mL saline suspension is created and administered as follows:
- Bacillus Calmette-Guerin (BCG) (Connaught strain) 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.
- Bacillus Calmette-Guerin (BCG) (Connaught strain) 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

Lamm, et al. 2000 was a bit unclear about the schedule of maintenance therapy. This is my 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:
- Bacillus Calmette-Guerin (BCG) (Connaught strain) 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.
- Bacillus Calmette-Guerin (BCG) (Connaught strain) 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, Ojea, et al. 2007 (lower dose BCG, CUETO study 95011)

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
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 original article contains verified protocol 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

Doxorubicin (Adriamycin)

Regimen

Level of Evidence: Phase III

Inferior to BCG, included for reference purposes only.

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)

Regimen, Ojea, et al. 2007 (CUETO study 95011)

Level of Evidence: Phase III

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 original article contains verified protocol PubMed

Pirarubicin (THP)

Regimen, Ito, et al. 2013

Level of Evidence: Phase III

Pirarubicin was given within 48 hours after nephroureterectomy.

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. doi: 10.1200/JCO.2012.45.2128. Epub 2013 Mar 4. link to original article contains verified protocol PubMed

Placebo

Regimen

Level of Evidence: Phase III

No 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. doi: 10.1200/JCO.2012.45.2128. Epub 2013 Mar 4. link to original article contains verified protocol PubMed

Thiotepa (Thioplex)

Regimen

Level of Evidence: Phase III

Inferior to BCG, included for reference purposes only.

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)

GC: Gemcitabine, Cisplatin

Regimen #1, Dash, et al. 2008 - single-dose cisplatin

Level of Evidence: Retrospective

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 cycles x 4 cycles

Regimen #2, Dash, et al. 2008 - split-dose cisplatin

Level of Evidence: Retrospective

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 cycles x 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. doi: 10.1002/cncr.23848. link to original article contains verified protocol PubMed

CMV, MCV

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

Regimen #1, International Collaboration of Trialists 2011 (CMV)

Level of Evidence: Phase III

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
Cisplatin (Platinol) 100 mg/m2 IV once on day 2, before hydration
Folinic acid (Leucovorin) 15 mg PO/IV every 6 hours x 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 cycles x 3 cycles

Regimen #2, Shipley, et al. 1998 (MCV)

Level of Evidence: Phase III

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 cycles x 2 cycles

MCV was followed by concurrent chemoradiation.

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
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. doi: 10.1200/JCO.2010.32.3139. Epub 2011 Apr 18. link to original article contains verified protocol PubMed

MVAC

MVAC: Methotrexate, Vinblastine, Adriamycin, Cisplatin

Regimen

Level of Evidence: Phase III

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 x 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

No neoadjuvant therapy

Regimen

Level of Evidence: Phase III

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

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
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. doi: 10.1200/JCO.2010.32.3139. Epub 2011 Apr 18. link to original article contains verified protocol PubMed

Concurrent chemotherapy & radiation

Cisplatin & RT

Regimen, Shipley, et al. 1998 - RTOG 89-03

Level of Evidence: Non-randomized

Induction therapy

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)

21-day cycles x 2 cycles; 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)

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

Fluorouracil, Mitomycin, RT

Regimen

Level of Evidence: Phase III

Fluorouracil (5-FU) 500 mg/m2/day IV continuous infusion x 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. doi: 10.1056/NEJMoa1106106. link to original article contains verified protocol PubMed

Radiation therapy

Regimen

Level of Evidence: Phase III

Inferior to chemoradiation with fluorouracil, mitomycin, RT; included 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. doi: 10.1056/NEJMoa1106106. link to original article contains verified protocol PubMed

Chemotherapy for locally advanced or metastatic disease

Carboplatin & Gemcitabine (GC)

GC: Gemcitabine, Carboplatin

Regimen

Level of Evidence: Randomized Phase II, >20 per arm

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 cycles x up to 6 cycles, until progression of disease, unacceptable toxicity, or physician discretion based on patient's best interests

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 original article contains verified protocol PubMed

Carboplatin & Paclitaxel

Regimen

Level of Evidence: Phase II

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

21-day cycles x 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

CISCA: CISplatin, Cyclophosphamide, Adriamycin

Regimen

Level of Evidence: Phase III

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

21-day cycles x up to 6 cycles

Supportive medications:

Forced mannitol diuresis with cisplatin

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)

GC: Gemcitabine, Cisplatin
GP: Gemcitabine, Platinol

Regimen #1, von der Maase, et al. 2000 & Bellmunt, et al. 2012 (EORTC 30987)

Level of Evidence: Phase III

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

28-day cycles x 6 cycles, given until progression of disease or unacceptable toxicity

Regimen #2, Dogliotti, et al. 2007

Level of Evidence: Randomized Phase II, >20 per arm

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 cycles x up to 6 cycles, until progression of disease, unacceptable toxicity, or physician discretion based on patient's best interests

Regimen #3, Soto Parra, et al. 2002 - 3-week schedule

Level of Evidence: Randomized Phase II, >20 per arm

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

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

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

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"

Regimen #4, Soto Parra, et al. 2002 - 4-week schedule

Level of Evidence: Randomized Phase II, >20 per arm

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

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, 15

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

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"

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 original 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 Feb 27. [Epub ahead of print] link to original article contains verified protocol PubMed

Cisplatin, Gemcitabine, Paclitaxel (PCG)

PCG: Paclitaxel, Cisplatin, Gemcitabine

Regimen, Bellmunt, et al. 2012 (EORTC 30987)

Level of Evidence: Phase III

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 cycles x 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 Feb 27. [Epub ahead of print] link to original article contains verified protocol PubMed

Gemcitabine & Paclitaxel

Regimen

Level of Evidence: Phase II

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 cycles x 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

MVAC: Methotrexate, Vinblastine, Adriamycin, Cisplatin

Regimen #1, Sternberg, et al. 2001 (dose-dense EORTC 30924)

Level of Evidence: Phase III

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

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

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 3-7.

Regimen #2, Logothetis, et al. 1990; Sternberg, et al. 2001 (EORTC 30924); Han, et al. 2008

Level of Evidence: Phase III

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 x 6 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
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
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 original article contains verified protocol PubMed

Pemetrexed (Alimta)

Regimen

Level of Evidence: Phase II

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

@@ Line 42: / Line 42: @@
 # 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]
 # 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.sciencedirect.com/science/article/pii/S0022534705677075 link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/10737480 PubMed]
+==Doxorubicin (Adriamycin)==
+===Regimen===
+Level of Evidence:
+<span
+style="background:#00CD00;
+padding:3px 6px 3px 6px;
+border-color:black;
+border-width:2px;
+border-style:solid;">Phase III</span>
+''Inferior to BCG, included for reference purposes only.''
+*[[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. [http://www.ncbi.nlm.nih.gov/pubmed/2106041 PubMed]
 ==Mitomycin (Mutamycin)==
 ===Regimen, Ojea, et al. 2007 (CUETO study 95011)===
+Level of Evidence:
+<span
+style="background:#00CD00;
+padding:3px 6px 3px 6px;
+border-color:black;
+border-width:2px;
+border-style:solid;">Phase III</span>
 ''Treatment begins 14 to 21 days after transurethral resection of bladder cancer.''
 ====Induction therapy====
@@ Line 63: / Line 89: @@
 ===Regimen, Ito, et al. 2013===
+Level of Evidence:
+<span
+style="background:#00CD00;
+padding:3px 6px 3px 6px;
+border-color:black;
+border-width:2px;
+border-style:solid;">Phase III</span>
 ''Pirarubicin was given within 48 hours after nephroureterectomy.''
 *[[Pirarubicin (THP)]] 30 mg in 30 mL normal saline intravesicularly, delivered through a catheter into the bladder, and retained for 30 minutes
@@ Line 70: / Line 104: @@
 ===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. doi: 10.1200/JCO.2012.45.2128. 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]
+==Placebo==
+===Regimen===
+Level of Evidence:
+<span
+style="background:#00CD00;
+padding:3px 6px 3px 6px;
+border-color:black;
+border-width:2px;
+border-style:solid;">Phase III</span>
+''No 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. doi: 10.1200/JCO.2012.45.2128. 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]
+==Thiotepa (Thioplex)==
+===Regimen===
+Level of Evidence:
+<span
+style="background:#00CD00;
+padding:3px 6px 3px 6px;
+border-color:black;
+border-width:2px;
+border-style:solid;">Phase III</span>
+''Inferior to BCG, included for reference purposes only.''
+*[[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. [http://www.ncbi.nlm.nih.gov/pubmed/2106041 PubMed]
 =Neoadjuvant chemotherapy=
@@ Line 76: / Line 144: @@
 ===Regimen #1, Dash, et al. 2008 - single-dose cisplatin===
+Level of Evidence:
+<span
+style="background:#ff0000;
+padding:3px 6px 3px 6px;
+border-color:black;
+border-width:2px;
+border-style:solid;">Retrospective</span>
 *[[Cisplatin (Platinol)]] 70 mg/m2 IV once on day 1
-*[[Gemcitabine (Gemzar)]] 1000 mg/m2 IV once daily on days 1 & 8
+*[[Gemcitabine (Gemzar)]] 1000 mg/m2 IV once per day on days 1 & 8
 '''21-day cycles x 4 cycles'''
 ===Regimen #2, Dash, et al. 2008 - split-dose cisplatin===
-*[[Cisplatin (Platinol)]] 35 mg/m2 IV once daily on days 1 & 8
+Level of Evidence:
-*[[Gemcitabine (Gemzar)]] 1000 mg/m2 IV once daily on days 1 & 8
+<span
+style="background:#ff0000;
+padding:3px 6px 3px 6px;
+border-color:black;
+border-width:2px;
+border-style:solid;">Retrospective</span>
+*[[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 cycles x 4 cycles'''
@@ Line 90: / Line 174: @@
 # 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. doi: 10.1002/cncr.23848. [http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2585515/ link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/18823036 PubMed]
-==CMV==
+==CMV, MCV==
 CMV: '''<u>C</u>'''isplatin, '''<u>M</u>'''ethotrexate, '''<u>V</u>'''inblastine
+MCV: '''<u>M</u>'''ethotrexate, '''<u>C</u>'''isplatin, '''<u>V</u>'''inblastine
+===Regimen #1, International Collaboration of Trialists 2011 (CMV)===
+Level of Evidence:
+<span
+style="background:#00CD00;
+padding:3px 6px 3px 6px;
+border-color:black;
+border-width:2px;
+border-style:solid;">Phase III</span>
-===Regimen===
+*[[Methotrexate (MTX)]] 30 mg/m2 IV bolus once per day on days 1 & 8
-*[[Methotrexate (MTX)]] 30 mg/m2 IV bolus once daily on days 1 & 8
+*[[Vinblastine (Velban)]] 4 mg/m2 IV bolus once per day on days 1 & 8
-*[[Vinblastine (Velban)]] 4 mg/m2 IV bolus once daily on days 1 & 8
 *[[Cisplatin (Platinol)]] 100 mg/m2 IV once on day 2, before hydration
 *[[Folinic acid (Leucovorin)]] 15 mg PO/IV every 6 hours x 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 cycles x 3 cycles'''
+===Regimen #2, Shipley, et al. 1998 (MCV)===
+Level of Evidence:
+<span
+style="background:#00CD00;
+padding:3px 6px 3px 6px;
+border-color:black;
+border-width:2px;
+border-style:solid;">Phase III</span>
+*[[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 cycles x 2 cycles'''
+''MCV was followed by concurrent chemoradiation.''
 ===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]
 # 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. doi: 10.1200/JCO.2010.32.3139. 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]
@@ Line 108: / Line 219: @@
 ===Regimen===
-*[[Methotrexate (MTX)]] 30 mg/m2 IV once daily on days 1, 15, 22
+Level of Evidence:
-*[[Vinblastine (Velban)]] 3 mg/m2 IV once daily on days 2, 15, 22
+<span
+style="background:#00CD00;
+padding:3px 6px 3px 6px;
+border-color:black;
+border-width:2px;
+border-style:solid;">Phase III</span>
+*[[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
@@ Line 117: / Line 236: @@
 ===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]
+==No neoadjuvant therapy==
+===Regimen===
+Level of Evidence:
+<span
+style="background:#00CD00;
+padding:3px 6px 3px 6px;
+border-color:black;
+border-width:2px;
+border-style:solid;">Phase III</span>
+''No preoperative treatment; used as a comparator arm and here for reference purposes only.''
+===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]
+# 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. doi: 10.1200/JCO.2010.32.3139. 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]
 =Concurrent chemotherapy & radiation=
 ==Cisplatin & RT==
 ===Regimen, Shipley, et al. 1998 - RTOG 89-03===
+Level of Evidence:
+<span
+style="background:#EEEE00;
+padding:3px 6px 3px 6px;
+border-color:black;
+border-width:2px;
+border-style:solid;">Non-randomized</span>
 ====Induction therapy====
-*[[Cisplatin (Platinol)]] 100 mg/m2 IV once daily on days 1 & 22
+*[[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)
@@ Line 137: / Line 281: @@
 ===Regimen===
+Level of Evidence:
+<span
+style="background:#00CD00;
+padding:3px 6px 3px 6px;
+border-color:black;
+border-width:2px;
+border-style:solid;">Phase III</span>
 *[[Fluorouracil (5-FU)]] 500 mg/m2/day IV continuous infusion x 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
@@ Line 142: / Line 294: @@
 **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. doi: 10.1056/NEJMoa1106106. [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]
+==Radiation therapy==
+===Regimen===
+Level of Evidence:
+<span
+style="background:#00CD00;
+padding:3px 6px 3px 6px;
+border-color:black;
+border-width:2px;
+border-style:solid;">Phase III</span>
+''Inferior to chemoradiation with fluorouracil, mitomycin, RT; included for reference purposes only.''
 ===References===
@@ Line 151: / Line 319: @@
 ===Regimen===
+Level of Evidence:
+<span
+style="background:#00CD00;
+padding:3px 6px 3px 6px;
+border-color:black;
+border-width:2px;
+border-style:solid;">Randomized Phase II, >20 per arm</span>
 *[[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 daily on days 1 & 8
+*[[Gemcitabine (Gemzar)]] 1250 mg/m2 IV over 30 to 60 minutes once per day on days 1 & 8
 '''21-day cycles x up to 6 cycles, until progression of disease, unacceptable toxicity, or physician discretion based on patient's best interests'''
@@ Line 161: / Line 337: @@
 ==Carboplatin & Paclitaxel==
 ===Regimen===
+Level of Evidence:
+<span
+style="background:#EEEE00;
+padding:3px 6px 3px 6px;
+border-color:black;
+border-width:2px;
+border-style:solid;">Phase II</span>
 *[[Carboplatin (Paraplatin)]] AUC 6 IV once on day 1
 *[[Paclitaxel (Taxol)]] 225 mg/m2 IV over 3 hours once on day 1
@@ Line 173: / Line 357: @@
 ===Regimen===
+Level of Evidence:
+<span
+style="background:#00CD00;
+padding:3px 6px 3px 6px;
+border-color:black;
+border-width:2px;
+border-style:solid;">Phase III</span>
 *[[Cyclophosphamide (Cytoxan)]] 650 mg/m2 IV once on day 1
 *[[Cisplatin (Platinol)]] 100 mg/m2 IV once on day 2
@@ Line 189: / Line 381: @@
 <br>GP: '''<u>G</u>'''emcitabine, '''<u>P</u>'''latinol
-===Regimen #1, von der Maase, et al. 2000 & Bellmunt, et al. 2012===
+===Regimen #1, von der Maase, et al. 2000 & Bellmunt, et al. 2012 (EORTC 30987)===
+Level of Evidence:
+<span
+style="background:#00CD00;
+padding:3px 6px 3px 6px;
+border-color:black;
+border-width:2px;
+border-style:solid;">Phase III</span>
 *[[Cisplatin (Platinol)]] 70 mg/m2 IV once on day 2
-*[[Gemcitabine (Gemzar)]] 1000 mg/m2 IV over 30 to 60 minutes once daily on days 1, 8, 15
+*[[Gemcitabine (Gemzar)]] 1000 mg/m2 IV over 30 to 60 minutes once per day on days 1, 8, 15
 '''28-day cycles x 6 cycles, given until progression of disease or unacceptable toxicity'''
 ===Regimen #2, Dogliotti, et al. 2007===
+Level of Evidence:
+<span
+style="background:#00CD00;
+padding:3px 6px 3px 6px;
+border-color:black;
+border-width:2px;
+border-style:solid;">Randomized Phase II, >20 per arm</span>
 *[[Cisplatin (Platinol)]] 70 mg/m2 IV once on day 2
-*[[Gemcitabine (Gemzar)]] 1250 mg/m2 IV over 30 to 60 minutes once daily on days 1 & 8
+*[[Gemcitabine (Gemzar)]] 1250 mg/m2 IV over 30 to 60 minutes once per day on days 1 & 8
 '''21-day cycles x up to 6 cycles, until progression of disease, unacceptable toxicity, or physician discretion based on patient's best interests'''
 ===Regimen #3, Soto Parra, et al. 2002 - 3-week schedule===
+Level of Evidence:
+<span
+style="background:#00CD00;
+padding:3px 6px 3px 6px;
+border-color:black;
+border-width:2px;
+border-style:solid;">Randomized Phase II, >20 per arm</span>
 ''Only a minority of patients in Soto Parra, et al. 2002 had bladder cancer.  The majority of patients had [[non-small cell lung cancer]].''
 *[[Cisplatin (Platinol)]] 70 mg/m2 IV over 30 to 60 minutes once on day 2
-*[[Gemcitabine (Gemzar)]] 1000 mg/m2 IV once daily on days 1 & 8
+*[[Gemcitabine (Gemzar)]] 1000 mg/m2 IV once per day on days 1 & 8
 '''21-day cycles x up to 6 cycles, until progression of disease, unacceptable toxicity, or physician discretion based on patient's best interests'''
@@ Line 214: / Line 430: @@
 ===Regimen #4, Soto Parra, et al. 2002 - 4-week schedule===
+Level of Evidence:
+<span
+style="background:#00CD00;
+padding:3px 6px 3px 6px;
+border-color:black;
+border-width:2px;
+border-style:solid;">Randomized Phase II, >20 per arm</span>
 ''Only a minority of patients in Soto Parra, et al. 2002 had bladder cancer.  The majority of patients had [[non-small cell lung cancer]].''
 *[[Cisplatin (Platinol)]] 70 mg/m2 IV over 30 to 60 minutes once on day 2
-*[[Gemcitabine (Gemzar)]] 1000 mg/m2 IV once daily on days 1, 8, 15
+*[[Gemcitabine (Gemzar)]] 1000 mg/m2 IV once per day on days 1, 8, 15
 '''28-day cycles x up to 6 cycles, until progression of disease, unacceptable toxicity, or physician discretion based on patient's best interests'''
@@ Line 234: / Line 458: @@
 PCG: '''<u>P</u>'''aclitaxel, '''<u>C</u>'''isplatin, '''<u>G</u>'''emcitabine
-===Regimen, Bellmunt, et al. 2012 - EORTC 30987===
+===Regimen, Bellmunt, et al. 2012 (EORTC 30987)===
+Level of Evidence:
+<span
+style="background:#00CD00;
+padding:3px 6px 3px 6px;
+border-color:black;
+border-width:2px;
+border-style:solid;">Phase III</span>
 *[[Cisplatin (Platinol)]] 70 mg/m2 IV once on day 1
-*[[Gemcitabine (Gemzar)]] 1000 mg/m2 IV over 30 to 60 minutes once daily on days 1 & 8
+*[[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 daily on days 1 & 8, given first
+*[[Paclitaxel (Taxol)]] 80 mg/m2 IV once per day on days 1 & 8, given first
 '''21-day cycles x up to 6 cycles'''
@@ Line 246: / Line 478: @@
 ==Gemcitabine & Paclitaxel==
 ===Regimen===
-*[[Gemcitabine (Gemzar)]] 1000 mg/m2 IV once daily on days 1, 8, 15
+Level of Evidence:
+<span
+style="background:#EEEE00;
+padding:3px 6px 3px 6px;
+border-color:black;
+border-width:2px;
+border-style:solid;">Phase II</span>
+*[[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
@@ Line 257: / Line 497: @@
 MVAC: '''<u>M</u>'''ethotrexate, '''<u>V</u>'''inblastine, '''<u>A</u>'''driamycin, '''<u>C</u>'''isplatin
-===Regimen #1, Sternberg, et al. 2001 & Sternberg, et al. 2006 - dose-dense EORTC 30924===
+===Regimen #1, Sternberg, et al. 2001 (dose-dense EORTC 30924)===
+Level of Evidence:
+<span
+style="background:#00CD00;
+padding:3px 6px 3px 6px;
+border-color:black;
+border-width:2px;
+border-style:solid;">Phase III</span>
 *[[Methotrexate (MTX)]] 30 mg/m2 IV once on day 1
 *[[Vinblastine (Velban)]] 3 mg/m2 IV once on day 2
@@ Line 266: / Line 514: @@
 Supportive medications:
-*[[Filgrastim (Neupogen)|G-CSF]] 240 ug/m2 SC once daily on days 4-10 (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 3-7.
+*[[Filgrastim (Neupogen)|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 10<sup>9</sup>/L.  In contrast to Sternberg, et al. 2001, Sternberg, et al. 2006 said G-CSF was given on days 3-7.
+===Regimen #2, Logothetis, et al. 1990; Sternberg, et al. 2001 (EORTC 30924); Han, et al. 2008===
+Level of Evidence:
+<span
+style="background:#00CD00;
+padding:3px 6px 3px 6px;
+border-color:black;
+border-width:2px;
+border-style:solid;">Phase III</span>
-===Regimen #2, Logothetis, et al. 1990; Sternberg, et al. 2001; Sternberg, et al. 2006; Han, et al. 2008===
+*[[Methotrexate (MTX)]] 30 mg/m2 IV once per day on days 1, 15, 22
-*[[Methotrexate (MTX)]] 30 mg/m2 IV once daily on days 1, 15, 22
+*[[Vinblastine (Velban)]] 3 mg/m2 IV once per day on days 2, 15, 22
-*[[Vinblastine (Velban)]] 3 mg/m2 IV once daily 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
@@ Line 278: / Line 534: @@
 ===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]
+# 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]
 # 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]
 # 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]
-# 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 original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/16330205 PubMed]
 ==Pemetrexed (Alimta)==
 ===Regimen===
+Level of Evidence:
+<span
+style="background:#EEEE00;
+padding:3px 6px 3px 6px;
+border-color:black;
+border-width:2px;
+border-style:solid;">Phase II</span>
 *[[Pemetrexed (Alimta)]] 500 mg/m2 IV over 10 minutes once on day 1

Difference between revisions of "Urothelial carcinoma"

Revision as of 01:42, 16 July 2013

Intravesical chemotherapy

Bacillus Calmette-Guerin (BCG)

Regimen #1, Lamm, et al. 2000 (intravesical & percutaneous, with maintenance therapy)

Induction therapy

Maintenance therapy

Regimen #2, Ojea, et al. 2007 (lower dose BCG, CUETO study 95011)

Induction therapy

Additional therapy

References

Doxorubicin (Adriamycin)

Regimen

References

Mitomycin (Mutamycin)

Regimen, Ojea, et al. 2007 (CUETO study 95011)

Induction therapy

Additional therapy

References

Pirarubicin (THP)

Regimen, Ito, et al. 2013

References

Placebo

Regimen

References

Thiotepa (Thioplex)

Regimen

References

Neoadjuvant chemotherapy

Cisplatin & Gemcitabine (GC)

Regimen #1, Dash, et al. 2008 - single-dose cisplatin

Regimen #2, Dash, et al. 2008 - split-dose cisplatin

References

CMV, MCV

Regimen #1, International Collaboration of Trialists 2011 (CMV)

Regimen #2, Shipley, et al. 1998 (MCV)

References

MVAC

Regimen

References

No neoadjuvant therapy

Regimen

References

Concurrent chemotherapy & radiation

Cisplatin & RT

Regimen, Shipley, et al. 1998 - RTOG 89-03

Induction therapy

Consolidation therapy

References

Fluorouracil, Mitomycin, RT

Regimen

References

Radiation therapy

Regimen

References

Chemotherapy for locally advanced or metastatic disease

Carboplatin & Gemcitabine (GC)

Regimen

References

Carboplatin & Paclitaxel

Regimen

References

CISCA

Regimen

References

Cisplatin & Gemcitabine (GC/GP)

Regimen #1, von der Maase, et al. 2000 & Bellmunt, et al. 2012 (EORTC 30987)

Regimen #2, Dogliotti, et al. 2007

Regimen #3, Soto Parra, et al. 2002 - 3-week schedule

Regimen #4, Soto Parra, et al. 2002 - 4-week schedule

References

Cisplatin, Gemcitabine, Paclitaxel (PCG)

Regimen, Bellmunt, et al. 2012 (EORTC 30987)

References

Gemcitabine & Paclitaxel

Regimen

References

MVAC

Regimen #1, Sternberg, et al. 2001 (dose-dense EORTC 30924)

Regimen #2, Logothetis, et al. 1990; Sternberg, et al. 2001 (EORTC 30924); Han, et al. 2008