Difference between revisions of "Urothelial carcinoma"

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===Regimen #1, Lamm et al. 2000 (intravesical & percutaneous, with maintenance therapy)===
 
===Regimen #1, Lamm et al. 2000 (intravesical & percutaneous, with maintenance therapy)===
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Level of Evidence:
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====Induction 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) 81 mg in 50.5 mL saline suspension is created and administered as follows:
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===Regimen #2, Ojea et al. 2007 (lower dose BCG, CUETO study 95011)===
 
===Regimen #2, Ojea et al. 2007 (lower dose BCG, CUETO study 95011)===
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Level of Evidence:
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''Treatment begins 14 to 21 days after transurethral resection of bladder cancer.''
 
''Treatment begins 14 to 21 days after transurethral resection of bladder cancer.''
 
====Induction therapy====
 
====Induction therapy====

Revision as of 16:36, 5 November 2013

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Intravesical chemotherapy

Bacillus Calmette-Guerin (BCG)

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

Level of Evidence: Phase III

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)

Level of Evidence: Phase III

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

Induction therapy

6-week course, then proceed to additional therapy

Additional therapy

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

References

  1. 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
  2. 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
  3. 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
  4. 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.

References

  1. 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

6-week course, then proceed to additional therapy

Additional therapy

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

References

  1. 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

  1. 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

  1. 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.

References

  1. 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

21-day cycles x 4 cycles

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

Level of Evidence: Retrospective

21-day cycles x 4 cycles

References

  1. 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

21-day cycles x 3 cycles

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

Level of Evidence: Phase III

28-day cycles x 2 cycles

MCV was followed by concurrent chemoradiation.

References

  1. 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
  2. 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

28-day cycles x 3 cycles

References

  1. 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

  1. 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
  2. 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

  1. 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

  1. 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

  1. 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

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

References

  1. 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

21-day cycles x up to 6 cycles

References

  1. 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

21-day cycles x up to 6 cycles

Supportive medications:

  • Forced mannitol diuresis with cisplatin

References

  1. 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

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

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.

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.

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

  1. 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
  2. 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
  3. 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
  4. 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

21-day cycles x up to 6 cycles

References

  1. 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

21-day cycles x up to 6 cycles

References

  1. 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

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

28-day cycles x 6 cycles (number of cycles and criteria to continue therapy varies depending on reference)

References

  1. 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
  2. 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
  3. 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
  4. 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
  5. 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

21-day cycles

References

  1. 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
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