Difference between revisions of "Urothelial carcinoma"
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MVAC: '''<u>M</u>'''ethotrexate, '''<u>V</u>'''inblastine, '''<u>A</u>'''driamycin, '''<u>C</u>'''isplatin | MVAC: '''<u>M</u>'''ethotrexate, '''<u>V</u>'''inblastine, '''<u>A</u>'''driamycin, '''<u>C</u>'''isplatin | ||
− | ===Regimen=== | + | ===Regimen #1, Grossman et al. 2003=== |
Level of Evidence: | Level of Evidence: | ||
<span | <span | ||
Line 233: | Line 233: | ||
'''28-day cycles x 3 cycles''' | '''28-day cycles x 3 cycles''' | ||
+ | |||
+ | ===Regimen #2, Qu et al. 2013 (dose-dense MVAC)=== | ||
+ | Level of Evidence: | ||
+ | <span style="background:#EEEE00; padding:3px 6px 3px 6px; border-color:black; border-width:2px; border-style:solid;">Phase II</span> | ||
+ | |||
+ | *[[Methotrexate (MTX)]] 30 mg/m2 IV over 30 minutes once on day 1 | ||
+ | *[[Vinblastine (Velban)]] 3 mg/m2 IV push once on day 2, given second on day 2, before cisplatin | ||
+ | *[[Doxorubicin (Adriamycin)]] 30 mg/m2 IV push once on day 2, given first on day 2, before vinblastine and cisplatin | ||
+ | *[[Cisplatin (Platinol)]] 70 mg/m2 IV in 1 liter normal saline once on day 2, given last on day 2, after doxorubicin and vinblastine | ||
+ | |||
+ | Supportive medications: | ||
+ | *[[Pegfilgrastim (Neulasta)]] 6 mg SC once on day 3 | ||
+ | *Use of Hesketh level 5 antiemetic regimen on day 2 (including aprepitant) was recommended | ||
+ | |||
+ | '''14-day cycles x 4 cycles'''; cystectomy to be performed 4 to 10 weeks after cycle 4 day 2 | ||
===References=== | ===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''' [http://www.ncbi.nlm.nih.gov/pubmed/12944571 PubMed] | ||
+ | # 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] | ||
==No neoadjuvant therapy== | ==No neoadjuvant therapy== |
Revision as of 05:08, 11 May 2014
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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
- 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, International Collaboration of Trialists 2011 (CMV)
Level of Evidence: Phase III
- 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 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
References
- 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 #1, Grossman et al. 2003
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
Regimen #2, Qu et al. 2013 (dose-dense MVAC)
Level of Evidence: Phase II
- Methotrexate (MTX) 30 mg/m2 IV over 30 minutes once on day 1
- Vinblastine (Velban) 3 mg/m2 IV push once on day 2, given second on day 2, before cisplatin
- Doxorubicin (Adriamycin) 30 mg/m2 IV push once on day 2, given first on day 2, before vinblastine and cisplatin
- Cisplatin (Platinol) 70 mg/m2 IV in 1 liter normal saline once on day 2, given last on day 2, after doxorubicin and vinblastine
Supportive medications:
- Pegfilgrastim (Neulasta) 6 mg SC once on day 3
- Use of Hesketh level 5 antiemetic regimen on day 2 (including aprepitant) was recommended
14-day cycles x 4 cycles; cystectomy to be performed 4 to 10 weeks after cycle 4 day 2
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
- 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. link to abstract
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
Neoadjuvant chemotherapy -> RT
MCV -> RT
Regimen, Zapatero, et al. 2000; Zapatero, et al. 2010; Zapatero, et al. 2012
Level of Evidence: 40 patients (Zapatero, et al. 2000); 41 patients (Zapatero, et al. 2010 & Zapatero, et al. 2012)
Patients in Zapatero, et al. 2000; Zapatero, et al. 2010; Zapatero, et al. 2012 had T2 to T4 Nx M0 disease.
Neoadjuvant chemotherapy
- 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 cycles x 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
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
- 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. doi: 10.1016/j.urolonc.2009.01.031. Epub 2009 Apr 11. link to original article contains verified protocol 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. doi: 10.1016/j.urology.2012.07.045. Epub 2012 Sep 19. link to original article PubMed
Neoadjuvant chemotherapy -> concurrent chemotherapy & radiation therapy
MCV -> Cisplatin & RT
Regimen, Shipley et al. 1998 (RTOG 89-03)
Level of Evidence: Phase III
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/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
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)
3-week course
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
Concurrent chemotherapy & radiation
Cisplatin & RT
Regimen #1, Shipley, et al. 1998 (RTOG 89-03)
Level of Evidence: Phase III
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)
3-week course
Regimen #2, Zapatero, et al. 2010 & Zapatero, et al. 2012 (weekly cisplatin)
Level of Evidence: 33 patients (Zapatero, et al. 2010); 34 patients (Zapatero, et al. 2012)
Patients in Zapatero, et al. 2010 & Zapatero, et al. 2012 had T2 to T4 N0 M0 disease.
Induction therapy
- Cisplatin (Platinol) 20 mg/m2 IV over 30 minutes given 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 given 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
- 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. doi: 10.1016/j.urolonc.2009.01.031. Epub 2009 Apr 11. link to original article contains verified protocol 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. doi: 10.1016/j.urology.2012.07.045. Epub 2012 Sep 19. link to original article contains verified protocol PubMed
Fluorouracil, Cisplatin, RT
Regimen, Kaufman, et al. 2000 (RTOG 95-06)
Level of Evidence: 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
Fluorouracil, Mitomycin, RT
Regimen, James, et al. 2012 (BC2001)
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 link to supplementary index contains verified protocol PubMed
Paclitaxel & RT
Regimen, Zapatero et al. 2012
Level of Evidence: 5 patients
Patients in Zapatero et al. 2012 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. doi: 10.1016/j.urology.2012.07.045. Epub 2012 Sep 19. 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
Adjuvant chemotherapy
Paclitaxel, Gemcitabine, & Cisplatin
Regimen, Paz-Ares et al 2010 (SOGUG 99/01)
Level of Evidence: Phase III
Patients in Paz-Ares, et al. 2010 (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.
Adjuvant therapy
Patients initially underwent cystectomy; the median time treatment started post-cystectomy was 48 days.
- Paclitaxel (Taxol) 80 mg mg/2 IV on days 1 & 8
- Gemcitabine (Gemzar) 1000 mg/m2 IV on days 1 & 8
- Cisplatin (Platinol) 70 mg/m2 IV on day 1
21-day cycles x 4 cycles
References
- 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 original article contains verified protocol
Concurrent chemotherapy & radiation -> adjuvant chemotherapy
Cisplatin & RT -> MCV
MCV: Methotrexate, Cisplatin, Vinblastine
Regimen, Hagan, et al. 2003 (RTOG 97-06)
Level of Evidence: Phase I/II
Patients in Hagan, et al. 2003 (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 given 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 given 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 cycles x 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
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, Sweeney, et al. 2006
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