Difference between revisions of "Urothelial carcinoma"
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− | + | ====Preceding treatment==== | |
+ | *[[#MCV|MCV]] versus [[#No_neoadjuvant_therapy|no neoadjuvant therapy]] | ||
====Chemoradiotherapy==== | ====Chemoradiotherapy==== | ||
*[[Cisplatin (Platinol)]] 100 mg/m<sup>2</sup> IV once per day on days 1 & 22 | *[[Cisplatin (Platinol)]] 100 mg/m<sup>2</sup> IV once per day on days 1 & 22 | ||
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− | + | ====Preceding treatment==== | |
+ | *[[#MCV|MCV]] x 2 | ||
====Chemoradiotherapy==== | ====Chemoradiotherapy==== | ||
*[[Cisplatin (Platinol)]] 70 mg/m<sup>2</sup> IV once per day on days 1 & 22 | *[[Cisplatin (Platinol)]] 70 mg/m<sup>2</sup> IV once per day on days 1 & 22 | ||
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− | + | ====Preceding treatment==== | |
+ | *Depending on response, treatment in '''Zapatero et al. 2000''' preceded by [[#MCV|MCV]] x 3 or cystectomy | ||
====Radiotherapy==== | ====Radiotherapy==== | ||
*Patients who had complete response received radiation therapy, 2 Gy fractions given 5 days per week, with total bladder dose of 60 Gy. Total dose to regional lymph nodes: 50 Gy. | *Patients who had complete response received radiation therapy, 2 Gy fractions given 5 days per week, with total bladder dose of 60 Gy. Total dose to regional lymph nodes: 50 Gy. | ||
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− | + | ====Preceding treatment==== | |
+ | *Depending on response, treatment preceded by [[#Cisplatin_.26_RT|cisplatin & RT induction]] or cystectomy | ||
====Chemoradiotherapy==== | ====Chemoradiotherapy==== | ||
*[[Cisplatin (Platinol)]] 100 mg/m<sup>2</sup> IV once on day 1 | *[[Cisplatin (Platinol)]] 100 mg/m<sup>2</sup> IV once on day 1 | ||
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− | + | ====Preceding treatment==== | |
+ | *Depending on response, treatment preceded by [[#Cisplatin_.26_RT|cisplatin & RT induction]] or cystectomy | ||
====Chemoradiotherapy==== | ====Chemoradiotherapy==== | ||
*[[Cisplatin (Platinol)]] 20 mg/m<sup>2</sup> IV over 30 minutes once per day on days 1, 2, 8, 9 (per Figure 1 of Zapatero, et al. 2010), '''given before radiation therapy''' | *[[Cisplatin (Platinol)]] 20 mg/m<sup>2</sup> IV over 30 minutes once per day on days 1, 2, 8, 9 (per Figure 1 of Zapatero, et al. 2010), '''given before radiation therapy''' | ||
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− | + | ====Preceding treatment==== | |
+ | *Depending on response, treatment preceded by [[#Cisplatin_.26_RT|cisplatin & RT induction]] or cystectomy. | ||
====Chemoradiotherapy==== | ====Chemoradiotherapy==== | ||
*[[Cisplatin (Platinol)]] 70 mg/m<sup>2</sup> IV once on day 1 | *[[Cisplatin (Platinol)]] 70 mg/m<sup>2</sup> IV once on day 1 | ||
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− | '' | + | ''Consolidation starts starts on week 8.'' |
+ | ====Preceding treatment==== | ||
+ | *[[#Cisplatin.2C_Fluorouracil.2C_RT|Cisplatin, 5-FU, RT induction]] | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
''Starts on week 8.'' | ''Starts on week 8.'' | ||
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− | ''Depending on response, treatment preceded by [[#Cisplatin.2C_Fluorouracil.2C_RT|cisplatin, fluorouracil, RT induction]] or cystectomy | + | ''Treatment starts on week 9.'' |
− | + | ====Preceding treatment==== | |
+ | *Depending on response, treatment preceded by [[#Cisplatin.2C_Fluorouracil.2C_RT|cisplatin, fluorouracil, RT induction]] or cystectomy | ||
====Chemoradiotherapy==== | ====Chemoradiotherapy==== | ||
*[[Cisplatin (Platinol)]] 15 mg/m<sup>2</sup> IV over 1 hour once per day on days 1 to 3, 15 to 17, '''given second''' | *[[Cisplatin (Platinol)]] 15 mg/m<sup>2</sup> IV over 1 hour once per day on days 1 to 3, 15 to 17, '''given second''' | ||
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− | '' | + | ''Consolidation starts starts on week 8.'' |
+ | ====Preceding treatment==== | ||
+ | *[[#Cisplatin.2C_Paclitaxel.2C_RT|Cisplatin, Paclitaxel, RT induction]] | ||
====Chemoradiotherapy==== | ====Chemoradiotherapy==== | ||
*[[Cisplatin (Platinol)]] 15 mg/m<sup>2</sup> IV once per day on days 1, 2, 8, 9 | *[[Cisplatin (Platinol)]] 15 mg/m<sup>2</sup> IV once per day on days 1, 2, 8, 9 | ||
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|} | |} | ||
− | '' | + | ''Consolidation starts starts on week 8.'' |
+ | ====Preceding treatment==== | ||
+ | *[[#Cisplatin.2C_Paclitaxel.2C_RT|Cisplatin, Paclitaxel, RT induction]] | ||
====Chemoradiotherapy==== | ====Chemoradiotherapy==== | ||
*[[Cisplatin (Platinol)]] 20 mg/m<sup>2</sup> IV once per day on days 1, 2, 8, 9 | *[[Cisplatin (Platinol)]] 20 mg/m<sup>2</sup> IV once per day on days 1, 2, 8, 9 | ||
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− | + | ====Preceding treatment==== | |
+ | *Depending on response, treatment preceded by [[#Paclitaxel_.26_RT|paclitaxel & RT induction]] or cystectomy. | ||
====Chemoradiotherapy==== | ====Chemoradiotherapy==== | ||
*[[Paclitaxel (Taxol)]] 50 mg/m<sup>2</sup> IV once per week, given 6 hours before radiation therapy | *[[Paclitaxel (Taxol)]] 50 mg/m<sup>2</sup> IV once per week, given 6 hours before radiation therapy |
Revision as of 02:02, 15 November 2017
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Is there a regimen missing from this list? Would you like to share a different dosage/schedule or an additional reference for a regimen? Have you noticed an error? Do you have an idea that will help the site grow to better meet your needs and the needs of many others? You are invited to contribute to the site.
31 regimens on this page
47 variants on this page
|
Guidelines
AUA, ASCO, ASTRO, SUO
- Treatment of Non-Metastatic Muscle-Invasive Bladder Cancer: AUA/ASCO/ASTRO/SUO Guideline (2017) PubMed
ESMO
NCCN
Intravesical chemotherapy
Bacillus Calmette-Guerin (BCG) monotherapy
Bacillus Calmette-Guerin (BCG) intravesicular chemotherapy in bladder cancer
Doxorubicin monotherapy
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Regimen
Study | Evidence | Comparator | Efficacy |
Martínez-Piñeiro et al. 1990 | Phase III | BCG | Inferior RFS |
Thiotepa | Not reported |
Inferior to BCG, included for reference purposes only.
Chemotherapy
- Doxorubicin (Adriamycin) 50 mg intravesicularly x 15 treatments
References
- Martínez-Piñeiro JA, Jiménez León J, Martínez-Piñeiro L Jr, Fiter L, Mosteiro JA, Navarro J, García Matres MJ, Cárcamo P. Bacillus Calmette-Guerin versus doxorubicin versus thiotepa: a randomized prospective study in 202 patients with superficial bladder cancer. J Urol. 1990 Mar;143(3):502-6. PubMed
Mitomycin monotherapy
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Regimen
Study | Evidence | Comparator | Efficacy |
Ojea et al. 2007 (CUETO study 95011) | Phase III | Low-dose BCG | Inferior DFS |
Very-low-dose BCG | Seems not superior |
Treatment begins 14 to 21 days after transurethral resection of bladder cancer.
Chemotherapy, part 1
- Mitomycin (Mutamycin) 30 mg intravesicularly once per day on days 1, 8, 15, 22, 29, 36
6-week course, then proceed to additional therapy
Chemotherapy, part 2
- Mitomycin (Mutamycin) 30 mg intravesicularly once every 2 weeks
12-week course; 6 doses given during this course (i.e. once on weeks 1, 3, 5, 7, 9, 11)
References
- Ojea A, Nogueira JL, Solsona E, Flores N, Gómez JM, Molina JR, Chantada V, Camacho JE, Piñeiro LM, Rodríguez RH, Isorna S, Blas M, Martínez-Piñeiro JA, Madero R; CUETO Group (Club Urológico Español De Tratamiento Oncológico). A multicentre, randomised prospective trial comparing three intravesical adjuvant therapies for intermediate-risk superficial bladder cancer: low-dose bacillus Calmette-Guerin (27 mg) versus very low-dose bacillus Calmette-Guerin (13.5 mg) versus mitomycin C. Eur Urol. 2007 Nov;52(5):1398-406. Epub 2007 Apr 27. link to SD article contains verified protocol PubMed
Pirarubicin monotherapy
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Regimen
Study | Evidence | Comparator | Efficacy |
Ito et al. 2013 (THP Monotherapy Study Group Trial) | Phase III | Observation | Seems to have superior RFS |
Pirarubicin was given within 48 hours after nephroureterectomy.
Chemotherapy
- Pirarubicin (THP) 30 mg in 30 mL normal saline intravesicularly, delivered through a catheter into the bladder, and retained for 30 minutes
1 dose
References
- Ito A, Shintaku I, Satoh M, Ioritani N, Aizawa M, Tochigi T, Kawamura S, Aoki H, Numata I, Takeda A, Namiki S, Namima T, Ikeda Y, Kambe K, Kyan A, Ueno S, Orikasa K, Katoh S, Adachi H, Tokuyama S, Ishidoya S, Yamaguchi T, Arai Y. Prospective randomized phase II trial of a single early intravesical instillation of pirarubicin (THP) in the prevention of bladder recurrence after nephroureterectomy for upper urinary tract urothelial carcinoma: the THP Monotherapy Study Group Trial. J Clin Oncol. 2013 Apr 10;31(11):1422-7. Epub 2013 Mar 4. link to original article contains verified protocol PubMed
Placebo or observation
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Regimen
Study | Evidence | Comparator | Efficacy |
Ito et al. 2013 | Phase III | Pirarubicin | Seems to have inferior RFS |
No active antineoplastic treatment; used as a comparator arm and included for reference purposes only.
References
- Ito A, Shintaku I, Satoh M, Ioritani N, Aizawa M, Tochigi T, Kawamura S, Aoki H, Numata I, Takeda A, Namiki S, Namima T, Ikeda Y, Kambe K, Kyan A, Ueno S, Orikasa K, Katoh S, Adachi H, Tokuyama S, Ishidoya S, Yamaguchi T, Arai Y. Prospective randomized phase II trial of a single early intravesical instillation of pirarubicin (THP) in the prevention of bladder recurrence after nephroureterectomy for upper urinary tract urothelial carcinoma: the THP Monotherapy Study Group Trial. J Clin Oncol. 2013 Apr 10;31(11):1422-7. Epub 2013 Mar 4. link to original article contains verified protocol PubMed
Thiotepa monotherapy
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Regimen
Study | Evidence | Comparator | Efficacy |
Martínez-Piñeiro et al. 1990 | Phase III | BCG | Inferior RFS |
Doxorubicin | Not reported |
Inferior to BCG, included for reference purposes only.
Chemotherapy
- Thiotepa (Thioplex) 50 mg intravesicularly x 15 treatments
References
- Martínez-Piñeiro JA, Jiménez León J, Martínez-Piñeiro L Jr, Fiter L, Mosteiro JA, Navarro J, García Matres MJ, Cárcamo P. Bacillus Calmette-Guerin versus doxorubicin versus thiotepa: a randomized prospective study in 202 patients with superficial bladder cancer. J Urol. 1990 Mar;143(3):502-6. PubMed
Neoadjuvant chemotherapy
Cisplatin & Gemcitabine
Cisplatin & Gemcitabine for bladder cancer, neoadjuvant
MCV
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CMV: Cisplatin, Methotrexate, Vinblastine
MCV: Methotrexate, Cisplatin, Vinblastine
Regimen #1
Study | Evidence | Comparator | Efficacy |
International Collaboration of Trialists et al. 1999 (BA06 30894) | Phase III | No neoadjuvant therapy | Seems to have superior OS |
Zapatero et al. 2000 | Non-randomized |
Patients in Zapatero et al. 2000 had T2 to T4 Nx M0 disease.
Chemotherapy
- Methotrexate (MTX) 30 mg/m2 IV bolus once per day on days 1 & 8
- Cisplatin (Platinol) 100 mg/m2 IV once on day 2, before hydration
- Vinblastine (Velban) 4 mg/m2 IV bolus once per day on days 1 & 8
Supportive medications
- BA06 30894: Folinic acid (Leucovorin) 15 mg PO/IV every 6 hours for 4 doses (total daily dose: 60 mg/m2) on days 2 & 9; given after hydration, with the first dose 24 hours after the previous day's dose of methotrexate
21-day cycle for 3 cycles
In Zapatero et al. 2000, after 3 cycles of chemotherapy, patients underwent cystoscopy, biopsy, and abdominal CT. Patients with complete response or who were not surgical candidates proceeded to radiotherapy consolidation which begins 4 to 6 weeks after completion of chemotherapy. Otherwise, patients proceeded to cystectomy.
Regimen #2
Study | Evidence | Comparator | Efficacy |
Tester et al. 1996 (RTOG 88-02) | Phase II | ||
Shipley et al. 1998 (RTOG 89-03) | Phase III | No neoadjuvant chemotherapy | Seems not superior |
Chemotherapy
- Methotrexate (MTX) 30 mg/m2 IV once per day on days 1, 15, 22
- Cisplatin (Platinol) 70 mg/m2 IV once on day 2
- Vinblastine (Velban) 3 mg/m2 IV once per day on days 2, 15, 22
28-day cycle for 2 cycles
Treatment followed by cisplatin & RT induction.
References
- Tester W, Caplan R, Heaney J, Venner P, Whittington R, Byhardt R, True L, Shipley W. Neoadjuvant combined modality program with selective organ preservation for invasive bladder cancer: results of Radiation Therapy Oncology Group phase II trial 8802. J Clin Oncol. 1996 Jan;14(1):119-26. link to original article contains verified protocol PubMed
- Shipley WU, Winter KA, Kaufman DS, Lee WR, Heney NM, Tester WR, Donnelly BJ, Venner PM, Perez CA, Murray KJ, Doggett RS, True LD. Phase III trial of neoadjuvant chemotherapy in patients with invasive bladder cancer treated with selective bladder preservation by combined radiation therapy and chemotherapy: initial results of Radiation Therapy Oncology Group 89-03. J Clin Oncol. 1998 Nov;16(11):3576-83. link to original article contains verified protocol PubMed
- Pooled Update: Efstathiou JA, Bae K, Shipley WU, Kaufman DS, Hagan MP, Heney NM, Sandler HM. Late pelvic toxicity after bladder-sparing therapy in patients with invasive bladder cancer: RTOG 89-03, 95-06, 97-06, 99-06. J Clin Oncol. 2009 Sep 1;27(25):4055-61. link to original article link to PMC article PubMed
- Pooled Update: Mak RH, Hunt D, Shipley WU, Efstathiou JA, Tester WJ, Hagan MP, Kaufman DS, Heney NM, Zietman AL. Long-Term Outcomes in Patients With Muscle-Invasive Bladder Cancer After Selective Bladder-Preserving Combined-Modality Therapy: A Pooled Analysis of Radiation Therapy Oncology Group Protocols 8802, 8903, 9506, 9706, 9906, and 0233. J Clin Oncol. 2014 Dec 1;32(34):3801-9. Epub 2014 Nov 3. link to original article contains verified protocol link to PMC article PubMed
- Neoadjuvant cisplatin, methotrexate, and vinblastine chemotherapy for muscle-invasive bladder cancer: a randomised controlled trial. International collaboration of trialists. Lancet. 1999 Aug 14;354(9178):533-40. Erratum in: Lancet 1999 Nov 6;354(9190):1650. link to original article PubMed
- Update: International Collaboration of Trialists; Medical Research Council Advanced Bladder Cancer Working Party (now the National Cancer Research Institute Bladder Cancer Clinical Studies Group); European Organisation for Research and Treatment of Cancer Genito-Urinary Tract Cancer Group; Australian Bladder Cancer Study Group; National Cancer Institute of Canada Clinical Trials Group; Finnbladder; Norwegian Bladder Cancer Study Group; Club Urologico Espanol de Tratamiento Oncologico Group, Griffiths G, Hall R, Sylvester R, Raghavan D, Parmar MK. International phase III trial assessing neoadjuvant cisplatin, methotrexate, and vinblastine chemotherapy for muscle-invasive bladder cancer: long-term results of the BA06 30894 trial. J Clin Oncol. 2011 Jun 1;29(16):2171-7. Epub 2011 Apr 18. link to original article contains verified protocol link to PMC article PubMed
- Zapatero A, Martín de Vidales C, Marín A, Cerezo L, Arellano R, Rabadán M, Pérez-Torrubia A. Invasive bladder cancer: a single-institution experience with bladder-sparing approach. Int J Cancer. 2000 Oct 20;90(5):287-94. link to original article contains 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. 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. Epub 2012 Sep 19. link to original article PubMed
MVAC
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MVAC: Methotrexate, Vinblastine, Adriamycin (Doxorubicin), Cisplatin
Regimen
Study | Evidence | Comparator | Efficacy |
Grossman et al. 2003 (SWOG S8710) | Phase III | No neoadjuvant therapy | Might have superior OS |
Chemotherapy
- Methotrexate (MTX) 30 mg/m2 IV once per day on days 1, 15, 22
- Vinblastine (Velban) 3 mg/m2 IV once per day on days 2, 15, 22
- Doxorubicin (Adriamycin) 30 mg/m2 IV once on day 2
- Cisplatin (Platinol) 70 mg/m2 IV once on day 2
28-day cycle for 3 cycles
References
- Grossman HB, Natale RB, Tangen CM, Speights VO, Vogelzang NJ, Trump DL, deVere White RW, Sarosdy MF, Wood DP Jr, Raghavan D, Crawford ED. Neoadjuvant chemotherapy plus cystectomy compared with cystectomy alone for locally advanced bladder cancer. N Engl J Med. 2003 Aug 28;349(9):859-66. link to original article contains verified protocol PubMed
- Kitamura H, Tsukamoto T, Shibata T, Masumori N, Fujimoto H, Hirao Y, Fujimoto K, Kitamura Y, Tomita Y, Tobisu K, Niwakawa M, Naito S, Eto M, Kakehi Y; Urologic Oncology Study Group of the Japan Clinical Oncology Group. Randomised phase III study of neoadjuvant chemotherapy with methotrexate, doxorubicin, vinblastine and cisplatin followed by radical cystectomy compared with radical cystectomy alone for muscle-invasive bladder cancer: Japan Clinical Oncology Group Study JCOG0209. Ann Oncol. 2014 Jun;25(6):1192-8. link to original article PubMed
MVAC (dose-dense/accelerated)
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ddMVAC: dose-dense Methotrexate, Vinblastine, Adriamycin (Doxorubicin), Cisplatin
AMVAC: Accelerated Methotrexate, Vinblastine, Adriamycin (Doxorubicin), Cisplatin
Regimen #1, dose-dense MVAC
Study | Evidence |
Choueiri et al. 2014 | Phase II |
Chemotherapy
- Methotrexate (MTX) 30 mg/m2 IV over 30 minutes once on day 1
- Vinblastine (Velban) 3 mg/m2 IV push once on day 2
- Doxorubicin (Adriamycin) 30 mg/m2 IV push once on day 2
- Cisplatin (Platinol) 70 mg/m2 IV in 1 liter normal saline once on day 2
Supportive medications
- Pegfilgrastim (Neulasta) 6 mg SC once on day 3 (approximately 24 hours after day 2 chemotherapy)
14-day cycle for 4 cycles
Cystectomy to be performed 4 to 10 weeks after completion of chemotherapy.
Regimen #2, accelerated MVAC
Study | Evidence |
Plimack et al. 2014 | Phase II |
Chemotherapy
- Methotrexate (MTX) 30 mg/m2 IV over 30 minutes once on day 1
- Vinblastine (Velban) 3 mg/m2 IV push once on day 2
- Doxorubicin (Adriamycin) 30 mg/m2 IV push once on day 2
- Cisplatin (Platinol) 70 mg/m2 IV in 1 liter normal saline once on day 2
- Split dose could be used at physician discretion for patients with CrCl less than 60 mL/min/1.73m2: 35 mg/m2 IV once per day on days 1 & 2
Supportive medications
- Pegfilgrastim (Neulasta) 6 mg SC once 24 to 48 hours after completion of chemotherapy
- Antiemetics used often included Aprepitant (Emend), Ondansetron (Zofran), and Dexamethasone (Decadron) but were not specified by the trial.
14-day cycle for 3 cycles
Radical cystectomy with bilateral lymphadenectomy to be done within 4 to 8 weeks after the last cycle of chemotherapy.
References
- Choueiri TK, Jacobus S, Bellmunt J, Qu A, Appleman LJ, Tretter C, Bubley GJ, Stack EC, Signoretti S, Walsh M, Steele G, Hirsch M, Sweeney CJ, Taplin ME, Kibel AS, Krajewski KM, Kantoff PW, Ross RW, Rosenberg JE. Neoadjuvant dose-dense methotrexate, vinblastine, doxorubicin, and cisplatin with pegfilgrastim support in muscle-invasive urothelial cancer: pathologic, radiologic, and biomarker correlates. J Clin Oncol. 2014 Jun 20;32(18):1889-94. Epub 2014 May 12. link to original article contains verified protocol PubMed
- Plimack ER, Hoffman-Censits JH, Viterbo R, Trabulsi EJ, Ross EA, Greenberg RE, Chen DY, Lallas CD, Wong YN, Lin J, Kutikov A, Dotan E, Brennan TA, Palma N, Dulaimi E, Mehrazin R, Boorjian SA, Kelly WK, Uzzo RG, Hudes GR. Accelerated methotrexate, vinblastine, doxorubicin, and cisplatin is safe, effective, and efficient neoadjuvant treatment for muscle-invasive bladder cancer: results of a multicenter phase II study with molecular correlates of response and toxicity. J Clin Oncol. 2014 Jun 20;32(18):1895-901. Epub 2014 May 12. link to original article contains verified protocol link to PMC article PubMed
No neoadjuvant therapy
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Regimen
Study | Evidence | Comparator | Efficacy |
International Collaboration of Trialists et al. 1999 (BA06 30894) | Phase III | CMV | Seems to have inferior OS |
Grossman et al. 2003 (SWOG S8710) | Phase III | MVAC | Might have inferior OS |
No preoperative treatment; used as a comparator arm and here for reference purposes only.
References
- Neoadjuvant cisplatin, methotrexate, and vinblastine chemotherapy for muscle-invasive bladder cancer: a randomised controlled trial. International collaboration of trialists. Lancet. 1999 Aug 14;354(9178):533-40. Erratum in: Lancet 1999 Nov 6;354(9190):1650. link to original article PubMed
- Update: International Collaboration of Trialists; Medical Research Council Advanced Bladder Cancer Working Party (now the National Cancer Research Institute Bladder Cancer Clinical Studies Group); European Organisation for Research and Treatment of Cancer Genito-Urinary Tract Cancer Group; Australian Bladder Cancer Study Group; National Cancer Institute of Canada Clinical Trials Group; Finnbladder; Norwegian Bladder Cancer Study Group; Club Urologico Espanol de Tratamiento Oncologico Group, Griffiths G, Hall R, Sylvester R, Raghavan D, Parmar MK. International phase III trial assessing neoadjuvant cisplatin, methotrexate, and vinblastine chemotherapy for muscle-invasive bladder cancer: long-term results of the BA06 30894 trial. J Clin Oncol. 2011 Jun 1;29(16):2171-7. Epub 2011 Apr 18. link to original article contains verified protocol link to PMC article PubMed
- Grossman HB, Natale RB, Tangen CM, Speights VO, Vogelzang NJ, Trump DL, deVere White RW, Sarosdy MF, Wood DP Jr, Raghavan D, Crawford ED. Neoadjuvant chemotherapy plus cystectomy compared with cystectomy alone for locally advanced bladder cancer. N Engl J Med. 2003 Aug 28;349(9):859-66. link to original article contains verified protocol PubMed
- Kitamura H, Tsukamoto T, Shibata T, Masumori N, Fujimoto H, Hirao Y, Fujimoto K, Kitamura Y, Tomita Y, Tobisu K, Niwakawa M, Naito S, Eto M, Kakehi Y; Urologic Oncology Study Group of the Japan Clinical Oncology Group. Randomised phase III study of neoadjuvant chemotherapy with methotrexate, doxorubicin, vinblastine and cisplatin followed by radical cystectomy compared with radical cystectomy alone for muscle-invasive bladder cancer: Japan Clinical Oncology Group Study JCOG0209. Ann Oncol. 2014 Jun;25(6):1192-8. link to original article PubMed
Induction chemoradiotherapy
Cisplatin & RT
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RT: Radiation Therapy
Regimen #1
Study | Evidence |
Shipley et al. 1998 (RTOG 89-03) | Non-randomized portion of RCT |
Preceding treatment
- MCV versus no neoadjuvant therapy
Chemoradiotherapy
- Cisplatin (Platinol) 100 mg/m2 IV once per day on days 1 & 22
- Concurrent radiation therapy, 1.8 Gy fractions x 22 fractions, given 5 times per week (total dose: 39.6 Gy)
1 treatment course
Patient is restaged 4 weeks after completion of radiation with "examination under anesthesia, cystoscopy with tumor-site biopsy, and urinary cytology." Patients not in complete remission usually proceeded to cystectomy. Patients in compete remission usually proceeded to consolidation cisplatin & RT.
Regimen #2, weekly cisplatin
Study | Evidence |
Zapatero et al. 2000 | Non-randomized |
Hagan, et al. 2003 (RTOG 97-06) | Phase I/II |
Patients in Zapatero et al. 2000 had T2 to T4 N0 M0 disease. Patients in RTOG 97-06 had T2 to T4a N0 M0 disease without hydronephrosis.
Chemoradiotherapy
- Cisplatin (Platinol) 20 mg/m2 IV over 30 minutes once per day on days 1, 2, 8, 9, 15, 16 (per Figure 1 of Zapatero, et al. 2010), given before radiation therapy
- Concurrent radiation therapy according to one of the following:
- Both trials: 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.
- Zapatero et al. 2000 only: 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 cisplatin & RT. Nonresponders proceeded to cystectomy.
Regimen #3
Study | Evidence |
Tester et al. 1996 (RTOG 88-02) | Phase II |
Preceding treatment
- MCV x 2
Chemoradiotherapy
- Cisplatin (Platinol) 70 mg/m2 IV once per day on days 1 & 22
- Concurrent radiation therapy, 1.8 Gy fractions x 22 fractions (total dose: 39.6 Gy)
1 treatment course
Patient is restaged 2 weeks after completion of radiation with "examination under anesthesia, cystoscopy with tumor-site biopsy, urinary cytology, and computed tomographic scan of pelvis." Patients with complete response--no evidence of disease on this evaluation--proceeded to consolidation cisplatin & RT. Patients without complete response proceeded immediately to cystectomy.
References
- Tester W, Caplan R, Heaney J, Venner P, Whittington R, Byhardt R, True L, Shipley W. Neoadjuvant combined modality program with selective organ preservation for invasive bladder cancer: results of Radiation Therapy Oncology Group phase II trial 8802. J Clin Oncol. 1996 Jan;14(1):119-26. link to original article contains verified protocol PubMed
- Shipley WU, Winter KA, Kaufman DS, Lee WR, Heney NM, Tester WR, Donnelly BJ, Venner PM, Perez CA, Murray KJ, Doggett RS, True LD. Phase III trial of neoadjuvant chemotherapy in patients with invasive bladder cancer treated with selective bladder preservation by combined radiation therapy and chemotherapy: initial results of Radiation Therapy Oncology Group 89-03. J Clin Oncol. 1998 Nov;16(11):3576-83. link to original article contains verified protocol PubMed
- Pooled Update: Efstathiou JA, Bae K, Shipley WU, Kaufman DS, Hagan MP, Heney NM, Sandler HM. Late pelvic toxicity after bladder-sparing therapy in patients with invasive bladder cancer: RTOG 89-03, 95-06, 97-06, 99-06. J Clin Oncol. 2009 Sep 1;27(25):4055-61. link to original article link to PMC article PubMed
- Pooled Update: Mak RH, Hunt D, Shipley WU, Efstathiou JA, Tester WJ, Hagan MP, Kaufman DS, Heney NM, Zietman AL. Long-Term Outcomes in Patients With Muscle-Invasive Bladder Cancer After Selective Bladder-Preserving Combined-Modality Therapy: A Pooled Analysis of Radiation Therapy Oncology Group Protocols 8802, 8903, 9506, 9706, 9906, and 0233. J Clin Oncol. 2014 Dec 1;32(34):3801-9. Epub 2014 Nov 3. link to original article contains verified protocol link to PMC article PubMed
- Hagan MP, Winter KA, Kaufman DS, Wajsman Z, Zietman AL, Heney NM, Toonkel LM, Jones CU, Roberts JD, Shipley WU. RTOG 97-06: initial report of a phase I-II trial of selective bladder conservation using TURBT, twice-daily accelerated irradiation sensitized with cisplatin, and adjuvant MCV combination chemotherapy. Int J Radiat Oncol Biol Phys. 2003 Nov 1;57(3):665-72. link to original article contains verified protocol PubMed
- Pooled Update: Efstathiou JA, Bae K, Shipley WU, Kaufman DS, Hagan MP, Heney NM, Sandler HM. Late pelvic toxicity after bladder-sparing therapy in patients with invasive bladder cancer: RTOG 89-03, 95-06, 97-06, 99-06. J Clin Oncol. 2009 Sep 1;27(25):4055-61. link to original article link to PMC article PubMed
- Pooled Update: Mak RH, Hunt D, Shipley WU, Efstathiou JA, Tester WJ, Hagan MP, Kaufman DS, Heney NM, Zietman AL. Long-Term Outcomes in Patients With Muscle-Invasive Bladder Cancer After Selective Bladder-Preserving Combined-Modality Therapy: A Pooled Analysis of Radiation Therapy Oncology Group Protocols 8802, 8903, 9506, 9706, 9906, and 0233. J Clin Oncol. 2014 Dec 1;32(34):3801-9. Epub 2014 Nov 3. link to original article contains verified protocol link to PMC article PubMed
- Zapatero A, Martin de Vidales C, Arellano R, Bocardo G, Pérez M, Ríos P. Updated results of bladder-sparing trimodality approach for invasive bladder cancer. Urol Oncol. 2010 Jul-Aug;28(4):368-74. Epub 2009 Apr 11. link to original article contains verified protocol PubMed
- Update: Zapatero A, Martin De Vidales C, Arellano R, Ibañez Y, Bocardo G, Perez M, Rabadan M, García Vicente F, Cruz Conde JA, Olivier C. Long-term results of two prospective bladder-sparing trimodality approaches for invasive bladder cancer: neoadjuvant chemotherapy and concurrent radio-chemotherapy. Urology. 2012 Nov;80(5):1056-62. Epub 2012 Sep 19. link to original article contains verified protocol PubMed
Cisplatin, Fluorouracil, RT
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Regimen #1
Study | Evidence | Comparator |
Mitin et al. 2013 (RTOG 02-33) | Randomized Phase II | Cisplatin, Paclitaxel, RT |
Chemoradiotherapy
- Cisplatin (Platinol) 15 mg/m2 IV once per day on days 1 to 3, 8 to 10, 15 to 17
- Fluorouracil (5-FU) 400 mg/m2 IV once per day on days 1 to 3, 8 to 10, 15 to 17
- Concurrent radiation therapy, with BID RT, with at least 4 hours between radiation therapy sessions:
- 1.6 Gy fractions to the pelvis every morning on days 1 to 5, 8 to 12, 15 to 17
- 1.5 Gy fractions to the bladder every evening on days 1 to 5
- 1.5 Gy fractions to the tumor every evening on days 8 to 12, 15 to 17
- Total doses: pelvis: 20.8 Gy; whole bladder: 28.3 Gy; bladder tumor volume 40.3 Gy.
3-week course
On week 7, patients under reevaluation for response. Patients with less than stage T1 disease proceeded to cisplatin, 5-FU, RT consolidation. Patients with at least stage T1 disease proceeded to radical cystectomy on week 9, followed by adjuvant PGC.
Regimen #2
Study | Evidence |
Kaufman, et al. 2000 (RTOG 95-06) | Phase I/II |
Patients in RTOG 95-06 had clinical T2 to T4a Nx M0 disease without hydronephrosis and CrCl of at least 60 mL/min/1.73m2.
Chemoradiotherapy
- Cisplatin (Platinol) 15 mg/m2 IV over 1 hour once per day on days 1 to 3, 15 to 17, given second, before radiation
- Fluorouracil (5-FU) 400 mg/m2 IV push once per day on days 1 to 3, 15 to 17, given first
- 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 less than 50 x 109/L or ANC less than 1800/uL, had chemotherapy and radiation therapy held for at least one week, with therapy resuming when platelets were at least 100 x 109/L and ANC at least 1800/uL.
Supportive medications
- IV hydration at 500 mL/H (no total volume specified) prior to fluorouracil
17-day course
Treatment followed by repeat cystoscopy, biopsy, and urine cytology in week 7 or 8. Patients with complete response proceeded to consolidation cisplatin, fluorouracil, RT in week 9. Incomplete responders were recommended to undergo radical cystectomy.
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
- Pooled Update: Efstathiou JA, Bae K, Shipley WU, Kaufman DS, Hagan MP, Heney NM, Sandler HM. Late pelvic toxicity after bladder-sparing therapy in patients with invasive bladder cancer: RTOG 89-03, 95-06, 97-06, 99-06. J Clin Oncol. 2009 Sep 1;27(25):4055-61. link to original article link to PMC article PubMed
- Pooled Update: Mak RH, Hunt D, Shipley WU, Efstathiou JA, Tester WJ, Hagan MP, Kaufman DS, Heney NM, Zietman AL. Long-Term Outcomes in Patients With Muscle-Invasive Bladder Cancer After Selective Bladder-Preserving Combined-Modality Therapy: A Pooled Analysis of Radiation Therapy Oncology Group Protocols 8802, 8903, 9506, 9706, 9906, and 0233. J Clin Oncol. 2014 Dec 1;32(34):3801-9. Epub 2014 Nov 3. link to original article contains verified protocol link to PMC article PubMed
- Mitin T, Hunt D, Shipley WU, Kaufman DS, Uzzo R, Wu CL, Buyyounouski MK, Sandler H, Zietman AL. Transurethral surgery and twice-daily radiation plus paclitaxel-cisplatin or fluorouracil-cisplatin with selective bladder preservation and adjuvant chemotherapy for patients with muscle invasive bladder cancer (RTOG 0233): a randomised multicentre phase 2 trial. Lancet Oncol. 2013 Aug;14(9):863-72. contains verified protocol link to PMC article PubMed
- Pooled Update: Efstathiou JA, Bae K, Shipley WU, Kaufman DS, Hagan MP, Heney NM, Sandler HM. Late pelvic toxicity after bladder-sparing therapy in patients with invasive bladder cancer: RTOG 89-03, 95-06, 97-06, 99-06. J Clin Oncol. 2009 Sep 1;27(25):4055-61. link to original article link to PMC article PubMed
- Pooled Update: Mak RH, Hunt D, Shipley WU, Efstathiou JA, Tester WJ, Hagan MP, Kaufman DS, Heney NM, Zietman AL. Long-Term Outcomes in Patients With Muscle-Invasive Bladder Cancer After Selective Bladder-Preserving Combined-Modality Therapy: A Pooled Analysis of Radiation Therapy Oncology Group Protocols 8802, 8903, 9506, 9706, 9906, and 0233. J Clin Oncol. 2014 Dec 1;32(34):3801-9. Epub 2014 Nov 3. link to original article contains verified protocol link to PMC article PubMed
Cisplatin, Paclitaxel, RT
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Regimen #1
Study | Evidence | Comparator |
Mitin et al. 2013 (RTOG 02-33) | Randomized Phase II | Cisplatin, Fluorouracil, RT |
Chemoradiotherapy
- Cisplatin (Platinol) 15 mg/m2 IV once per day on days 1 to 3, 8 to 10, 15 to 17
- Paclitaxel (Taxol) 50 mg/m2 IV once per day on days 1, 8, 15
- Concurrent radiation therapy, with BID RT, with at least 4 hours between radiation therapy sessions:
- 1.6 Gy fractions to the pelvis every morning on days 1 to 5, 8 to 12, 15 to 17
- 1.5 Gy fractions to the bladder every evening on days 1 to 5
- 1.5 Gy fractions to the tumor every evening on days 8 to 12, 15 to 17
- Total doses: pelvis: 20.8 Gy; whole bladder: 28.3 Gy; bladder tumor volume 40.3 Gy.
3-week course
On week 7, patients under reevaluation for response. Patients with less than stage ypT1 disease proceeded to cisplatin, paclitaxel, RT consolidation. Patients with at least stage ypT1 disease proceeded to radical cystectomy on week 9, followed by adjuvant PGC.
Regimen #2
Study | Evidence |
Kaufman, et al. 2009 (RTOG 99-06) | Phase I/II |
Treatment starts 4 to 6 weeks after TURBT.
Chemoradiotherapy
- Cisplatin (Platinol) 20 mg/m2 IV once per day on days 1, 2, 8, 9, 15, 16
- Paclitaxel (Taxol) 50 mg/m2 IV once per day on days 1, 8, 15
- Concurrent radiation therapy, with BID RT on days 1 to 5, 8 to 12, 15 to 17; 4 to 6 hours between radiation sessions. Kaufman et al. 2009 (RTOG 99-06) was unclear about exact radiation treatment plan, but it appears to have been the same as described in Mitin et al. 2013 (RTOG 02-33), which used radiation as follows:
- 1.6 Gy fractions to the pelvis every morning on days 1 to 5, 8 to 12, 15 to 17
- 1.5 Gy fractions to the bladder every evening on days 1 to 5
- 1.5 Gy fractions to the tumor every evening on days 8 to 12, 15 to 17
- Total doses: pelvis: 20.8 Gy; whole bladder: 28.3 Gy; bladder tumor volume 40.3 Gy.
3-week course
On week 7, over 3 weeks after induction therapy, patients under reevaluation with exam under anesthesia, cystoscopy with tumor site biopsy, and urine cytology. Patients with less than stage ypT1 disease proceeded to cisplatin, paclitaxel, RT consolidation. Patients with at least stage ypT1 disease proceeded to radical cystectomy, followed by adjuvant cisplatin & gemcitabine. Note: The abstract of Kaufman, et al. 2009 said that patients with "greater than Stage T1 disease" were recommended for cystectomy, but Figure 1 clarified that it was greater than or equal to ypT1 disease.
References
- Kaufman DS, Winter KA, Shipley WU, Heney NM, Wallace HJ 3rd, Toonkel LM, Zietman AL, Tanguay S, Sandler HM. Phase I-II RTOG study (99-06) of patients with muscle-invasive bladder cancer undergoing transurethral surgery, paclitaxel, cisplatin, and twice-daily radiotherapy followed by selective bladder preservation or radical cystectomy and adjuvant chemotherapy. Urology. 2009 Apr;73(4):833-7. link to original article contains verified protocol PubMed
- Pooled Update: Efstathiou JA, Bae K, Shipley WU, Kaufman DS, Hagan MP, Heney NM, Sandler HM. Late pelvic toxicity after bladder-sparing therapy in patients with invasive bladder cancer: RTOG 89-03, 95-06, 97-06, 99-06. J Clin Oncol. 2009 Sep 1;27(25):4055-61. link to original article link to PMC article PubMed
- Pooled Update: Mak RH, Hunt D, Shipley WU, Efstathiou JA, Tester WJ, Hagan MP, Kaufman DS, Heney NM, Zietman AL. Long-Term Outcomes in Patients With Muscle-Invasive Bladder Cancer After Selective Bladder-Preserving Combined-Modality Therapy: A Pooled Analysis of Radiation Therapy Oncology Group Protocols 8802, 8903, 9506, 9706, 9906, and 0233. J Clin Oncol. 2014 Dec 1;32(34):3801-9. Epub 2014 Nov 3. link to original article contains verified protocol link to PMC article PubMed
- Mitin T, Hunt D, Shipley WU, Kaufman DS, Uzzo R, Wu CL, Buyyounouski MK, Sandler H, Zietman AL. Transurethral surgery and twice-daily radiation plus paclitaxel-cisplatin or fluorouracil-cisplatin with selective bladder preservation and adjuvant chemotherapy for patients with muscle invasive bladder cancer (RTOG 0233): a randomised multicentre phase 2 trial. Lancet Oncol. 2013 Aug;14(9):863-72. contains verified protocol link to PMC article PubMed
- Pooled Update: Efstathiou JA, Bae K, Shipley WU, Kaufman DS, Hagan MP, Heney NM, Sandler HM. Late pelvic toxicity after bladder-sparing therapy in patients with invasive bladder cancer: RTOG 89-03, 95-06, 97-06, 99-06. J Clin Oncol. 2009 Sep 1;27(25):4055-61. link to original article link to PMC article PubMed
- Pooled Update: Mak RH, Hunt D, Shipley WU, Efstathiou JA, Tester WJ, Hagan MP, Kaufman DS, Heney NM, Zietman AL. Long-Term Outcomes in Patients With Muscle-Invasive Bladder Cancer After Selective Bladder-Preserving Combined-Modality Therapy: A Pooled Analysis of Radiation Therapy Oncology Group Protocols 8802, 8903, 9506, 9706, 9906, and 0233. J Clin Oncol. 2014 Dec 1;32(34):3801-9. Epub 2014 Nov 3. link to original article contains verified protocol link to PMC article PubMed
Fluorouracil, Mitomycin, RT
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RT: Radiation Therapy
Regimen
Study | Evidence | Comparator | Efficacy |
James et al. 2012 (BC2001) | Phase III | Radiation therapy | Seems to have superior locoregional DFS |
Chemoradiotherapy
- Fluorouracil (5-FU) 500 mg/m2/day IV continuous infusion for 10 total days (total dose: 5000 mg/m2) during radiation fractions 1 to 5, 16 to 20
- Mitomycin (Mutamycin) 12 mg/m2 IV bolus once on day 1
- Radiation therapy given according to one of the following plans:
- Concurrent radiation therapy, 2.75 Gy fractions x 20 fractions (total dose: 55 Gy) over 4 weeks
- Concurrent radiation therapy, 2 Gy fractions x 32 fractions (total dose: 64 Gy) over 6.5 weeks
References
- James ND, Hussain SA, Hall E, Jenkins P, Tremlett J, Rawlings C, Crundwell M, Sizer B, Sreenivasan T, Hendron C, Lewis R, Waters R, Huddart RA; BC2001 Investigators. Radiotherapy with or without chemotherapy in muscle-invasive bladder cancer. N Engl J Med. 2012 Apr 19;366(16):1477-88. link to original article link to supplementary index contains verified protocol PubMed
Paclitaxel & RT
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Regimen
Study | Evidence |
Zapatero et al. 2012 | Non-randomized, <20 pts |
Patients who had "mild renal insufficiency" received paclitaxel instead of cisplatin and had T2 to T4 N0 M0 disease.
Chemoradiotherapy
- 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 paclitaxel & RT. Nonresponders proceeded to cystectomy.
References
- Zapatero A, Martin De Vidales C, Arellano R, Ibañez Y, Bocardo G, Perez M, Rabadan M, García Vicente F, Cruz Conde JA, Olivier C. Long-term results of two prospective bladder-sparing trimodality approaches for invasive bladder cancer: neoadjuvant chemotherapy and concurrent radio-chemotherapy. Urology. 2012 Nov;80(5):1056-62. Epub 2012 Sep 19. link to original article contains verified protocol PubMed
Radiation therapy
back to top |
Regimen
Study | Evidence | Comparator | Efficacy |
Zapatero et al. 2000 | Non-randomized | ||
James et al. 2012 (BC2001) | Phase III | Fluorouracil, Mitomycin, RT | Seems to have inferior locoregional DFS |
Preceding treatment
- Depending on response, treatment in Zapatero et al. 2000 preceded by MCV x 3 or cystectomy
Radiotherapy
- 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. 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. Epub 2012 Sep 19. link to original article PubMed
- James ND, Hussain SA, Hall E, Jenkins P, Tremlett J, Rawlings C, Crundwell M, Sizer B, Sreenivasan T, Hendron C, Lewis R, Waters R, Huddart RA; BC2001 Investigators. Radiotherapy with or without chemotherapy in muscle-invasive bladder cancer. N Engl J Med. 2012 Apr 19;366(16):1477-88. link to original article contains verified protocol PubMed
Consolidation chemoradiotherapy
Cisplatin & RT
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RT: Radiation Therapy
Regimen #1
Study | Evidence |
Shipley et al. 1998 (RTOG 89-03) | Non-randomized portion of RCT |
Preceding treatment
- Depending on response, treatment preceded by cisplatin & RT induction or cystectomy
Chemoradiotherapy
- Cisplatin (Platinol) 100 mg/m2 IV once on day 1
- Concurrent radiation therapy, 1.8 Gy fractions x 14 fractions, given 5 times per week (total dose in consolidation phase: 39.6 Gy; total overall dose in induction and consolidation phases: 64.8 Gy)
3-week course
Regimen #2, weekly cisplatin
Study | Evidence |
Zapatero et al. 2000 | Non-randomized |
Hagan, et al. 2003 (RTOG 97-06) | Phase I/II |
Preceding treatment
- Depending on response, treatment preceded by cisplatin & RT induction or cystectomy
Chemoradiotherapy
- Cisplatin (Platinol) 20 mg/m2 IV over 30 minutes once per day on days 1, 2, 8, 9 (per Figure 1 of Zapatero, et al. 2010), given before radiation therapy
- Concurrent radiation therapy according to ONE of the following:
- Both trials: 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.
- Zapatero et al. 2000 only: 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)
Treatment in RTOG 97-06 followed by adjuvant MCV.
Regimen #3
Study | Evidence |
Tester et al. 1996 (RTOG 88-02) | Phase II |
Preceding treatment
- Depending on response, treatment preceded by cisplatin & RT induction or cystectomy.
Chemoradiotherapy
- Cisplatin (Platinol) 70 mg/m2 IV once on day 1
- Concurrent radiation therapy, 1.8 Gy fractions x 14 fractions (total dose in consolidation phase: 25.2 Gy; total overall dose in induction and consolidation phases: 64.8 Gy)
3-week course
References
- Tester W, Caplan R, Heaney J, Venner P, Whittington R, Byhardt R, True L, Shipley W. Neoadjuvant combined modality program with selective organ preservation for invasive bladder cancer: results of Radiation Therapy Oncology Group phase II trial 8802. J Clin Oncol. 1996 Jan;14(1):119-26. link to original article contains verified protocol PubMed
- Shipley WU, Winter KA, Kaufman DS, Lee WR, Heney NM, Tester WR, Donnelly BJ, Venner PM, Perez CA, Murray KJ, Doggett RS, True LD. Phase III trial of neoadjuvant chemotherapy in patients with invasive bladder cancer treated with selective bladder preservation by combined radiation therapy and chemotherapy: initial results of Radiation Therapy Oncology Group 89-03. J Clin Oncol. 1998 Nov;16(11):3576-83. link to original article contains verified protocol PubMed
- Pooled Update: Efstathiou JA, Bae K, Shipley WU, Kaufman DS, Hagan MP, Heney NM, Sandler HM. Late pelvic toxicity after bladder-sparing therapy in patients with invasive bladder cancer: RTOG 89-03, 95-06, 97-06, 99-06. J Clin Oncol. 2009 Sep 1;27(25):4055-61. link to original article link to PMC article PubMed
- Pooled Update: Mak RH, Hunt D, Shipley WU, Efstathiou JA, Tester WJ, Hagan MP, Kaufman DS, Heney NM, Zietman AL. Long-Term Outcomes in Patients With Muscle-Invasive Bladder Cancer After Selective Bladder-Preserving Combined-Modality Therapy: A Pooled Analysis of Radiation Therapy Oncology Group Protocols 8802, 8903, 9506, 9706, 9906, and 0233. J Clin Oncol. 2014 Dec 1;32(34):3801-9. Epub 2014 Nov 3. link to original article contains verified protocol link to PMC article PubMed
- Hagan MP, Winter KA, Kaufman DS, Wajsman Z, Zietman AL, Heney NM, Toonkel LM, Jones CU, Roberts JD, Shipley WU. RTOG 97-06: initial report of a phase I-II trial of selective bladder conservation using TURBT, twice-daily accelerated irradiation sensitized with cisplatin, and adjuvant MCV combination chemotherapy. Int J Radiat Oncol Biol Phys. 2003 Nov 1;57(3):665-72. link to original article contains verified protocol PubMed
- Pooled Update: Efstathiou JA, Bae K, Shipley WU, Kaufman DS, Hagan MP, Heney NM, Sandler HM. Late pelvic toxicity after bladder-sparing therapy in patients with invasive bladder cancer: RTOG 89-03, 95-06, 97-06, 99-06. J Clin Oncol. 2009 Sep 1;27(25):4055-61. link to original article link to PMC article PubMed
- Pooled Update: Mak RH, Hunt D, Shipley WU, Efstathiou JA, Tester WJ, Hagan MP, Kaufman DS, Heney NM, Zietman AL. Long-Term Outcomes in Patients With Muscle-Invasive Bladder Cancer After Selective Bladder-Preserving Combined-Modality Therapy: A Pooled Analysis of Radiation Therapy Oncology Group Protocols 8802, 8903, 9506, 9706, 9906, and 0233. J Clin Oncol. 2014 Dec 1;32(34):3801-9. Epub 2014 Nov 3. link to original article contains verified protocol link to PMC article PubMed
- Zapatero A, Martin de Vidales C, Arellano R, Bocardo G, Pérez M, Ríos P. Updated results of bladder-sparing trimodality approach for invasive bladder cancer. Urol Oncol. 2010 Jul-Aug;28(4):368-74. Epub 2009 Apr 11. link to original article contains verified protocol PubMed
- Update: Zapatero A, Martin De Vidales C, Arellano R, Ibañez Y, Bocardo G, Perez M, Rabadan M, García Vicente F, Cruz Conde JA, Olivier C. Long-term results of two prospective bladder-sparing trimodality approaches for invasive bladder cancer: neoadjuvant chemotherapy and concurrent radio-chemotherapy. Urology. 2012 Nov;80(5):1056-62. Epub 2012 Sep 19. link to original article contains verified protocol PubMed
Cisplatin, Fluorouracil, RT
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Regimen #1
Study | Evidence | Comparator |
Mitin et al. 2013 (RTOG 02-33) | Randomized Phase II | Cisplatin, Paclitaxel, RT |
Consolidation starts starts on week 8.
Preceding treatment
Chemotherapy
Starts on week 8.
- Cisplatin (Platinol) 15 mg/m2 IV once per day on days 1, 2, 8, 9
- Fluorouracil (5-FU) 400 mg/m2 IV once per day on days 1 to 3, 8 to 10
- Concurrent radiation therapy, 1.5 Gy fractions x 16 fractions, given twice per day x 8 days. Total dose during consolidation is 24 Gy. Total dose after induction therapy and consolidation therapy: pelvis: 44.8 Gy; whole bladder: 52.3 Gy; bladder tumor volume 64.3 Gy.
2-week course
Treatment followed by adjuvant PGC.
Regimen #2
Study | Evidence |
Kaufman, et al. 2000 (RTOG 95-06) | Phase I/II |
Treatment starts on week 9.
Preceding treatment
- Depending on response, treatment preceded by cisplatin, fluorouracil, RT induction or cystectomy
Chemoradiotherapy
- Cisplatin (Platinol) 15 mg/m2 IV over 1 hour once per day on days 1 to 3, 15 to 17, given second
- Fluorouracil (5-FU) 400 mg/m2 IV push once per day on days 1 to 3, 15 to 17, given first
- 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 less than 50 x 109/L or ANC less than 1800/uL, had chemotherapy and radiation therapy held for at least one week, with therapy resuming when platelets were at least 100 x 109/L and ANC at least 1800/uL.
Supportive medications
- IV hydration at 500 mL/H (no total volume specified) prior to Fluorouracil (5-FU)
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
- Pooled Update: Efstathiou JA, Bae K, Shipley WU, Kaufman DS, Hagan MP, Heney NM, Sandler HM. Late pelvic toxicity after bladder-sparing therapy in patients with invasive bladder cancer: RTOG 89-03, 95-06, 97-06, 99-06. J Clin Oncol. 2009 Sep 1;27(25):4055-61. link to original article link to PMC article PubMed
- Pooled Update: Mak RH, Hunt D, Shipley WU, Efstathiou JA, Tester WJ, Hagan MP, Kaufman DS, Heney NM, Zietman AL. Long-Term Outcomes in Patients With Muscle-Invasive Bladder Cancer After Selective Bladder-Preserving Combined-Modality Therapy: A Pooled Analysis of Radiation Therapy Oncology Group Protocols 8802, 8903, 9506, 9706, 9906, and 0233. J Clin Oncol. 2014 Dec 1;32(34):3801-9. Epub 2014 Nov 3. link to original article contains verified protocol link to PMC article PubMed
- Mitin T, Hunt D, Shipley WU, Kaufman DS, Uzzo R, Wu CL, Buyyounouski MK, Sandler H, Zietman AL. Transurethral surgery and twice-daily radiation plus paclitaxel-cisplatin or fluorouracil-cisplatin with selective bladder preservation and adjuvant chemotherapy for patients with muscle invasive bladder cancer (RTOG 0233): a randomised multicentre phase 2 trial. Lancet Oncol. 2013 Aug;14(9):863-72. contains verified protocol link to PMC article PubMed
- Pooled Update: Efstathiou JA, Bae K, Shipley WU, Kaufman DS, Hagan MP, Heney NM, Sandler HM. Late pelvic toxicity after bladder-sparing therapy in patients with invasive bladder cancer: RTOG 89-03, 95-06, 97-06, 99-06. J Clin Oncol. 2009 Sep 1;27(25):4055-61. link to original article link to PMC article PubMed
- Pooled Update: Mak RH, Hunt D, Shipley WU, Efstathiou JA, Tester WJ, Hagan MP, Kaufman DS, Heney NM, Zietman AL. Long-Term Outcomes in Patients With Muscle-Invasive Bladder Cancer After Selective Bladder-Preserving Combined-Modality Therapy: A Pooled Analysis of Radiation Therapy Oncology Group Protocols 8802, 8903, 9506, 9706, 9906, and 0233. J Clin Oncol. 2014 Dec 1;32(34):3801-9. Epub 2014 Nov 3. link to original article contains verified protocol link to PMC article PubMed
Cisplatin, Paclitaxel, RT
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Regimen
Study | Evidence | Comparator |
Mitin et al. 2013 (RTOG 02-33) | Randomized Phase II | Cisplatin, 5-FU, RT |
Consolidation starts starts on week 8.
Preceding treatment
Chemoradiotherapy
- Cisplatin (Platinol) 15 mg/m2 IV once per day on days 1, 2, 8, 9
- Paclitaxel (Taxol) 50 mg/m2 IV once per day on days 1 & 8
- Concurrent radiation therapy, 1.5 Gy fractions x 16 fractions, given twice per day x 8 days. Total dose during consolidation is 24 Gy. Total dose after induction therapy and consolidation therapy: pelvis: 44.8 Gy; whole bladder: 52.3 Gy; bladder tumor volume 64.3 Gy.
2-week course
Treatment followed by adjuvant PGC.
Regimen #2
Study | Evidence |
Kaufman, et al. 2009 (RTOG 99-06) | Phase I/II |
Consolidation starts starts on week 8.
Preceding treatment
Chemoradiotherapy
- Cisplatin (Platinol) 20 mg/m2 IV once per day on days 1, 2, 8, 9
- Paclitaxel (Taxol) 50 mg/m2 IV once per day on days 1 & 8
- Concurrent radiation therapy, 1.5 Gy fractions x 16 fractions, given twice per day (4 to 6 hour interval between treatments) on days 1 to 5, 8 to 10. Total dose during consolidation is 24 Gy. Total dose after induction therapy and consolidation therapy: pelvis: 44.8 Gy; whole bladder: 52.3 Gy; bladder tumor volume 64.3 Gy.
2-week course
Treatment followed by adjuvant cisplatin & gemcitabine.
References
- Kaufman DS, Winter KA, Shipley WU, Heney NM, Wallace HJ 3rd, Toonkel LM, Zietman AL, Tanguay S, Sandler HM. Phase I-II RTOG study (99-06) of patients with muscle-invasive bladder cancer undergoing transurethral surgery, paclitaxel, cisplatin, and twice-daily radiotherapy followed by selective bladder preservation or radical cystectomy and adjuvant chemotherapy. Urology. 2009 Apr;73(4):833-7. link to original article contains verified protocol PubMed
- Pooled Update: Efstathiou JA, Bae K, Shipley WU, Kaufman DS, Hagan MP, Heney NM, Sandler HM. Late pelvic toxicity after bladder-sparing therapy in patients with invasive bladder cancer: RTOG 89-03, 95-06, 97-06, 99-06. J Clin Oncol. 2009 Sep 1;27(25):4055-61. link to original article link to PMC article PubMed
- Pooled Update: Mak RH, Hunt D, Shipley WU, Efstathiou JA, Tester WJ, Hagan MP, Kaufman DS, Heney NM, Zietman AL. Long-Term Outcomes in Patients With Muscle-Invasive Bladder Cancer After Selective Bladder-Preserving Combined-Modality Therapy: A Pooled Analysis of Radiation Therapy Oncology Group Protocols 8802, 8903, 9506, 9706, 9906, and 0233. J Clin Oncol. 2014 Dec 1;32(34):3801-9. Epub 2014 Nov 3. link to original article contains verified protocol link to PMC article PubMed
- Mitin T, Hunt D, Shipley WU, Kaufman DS, Uzzo R, Wu CL, Buyyounouski MK, Sandler H, Zietman AL. Transurethral surgery and twice-daily radiation plus paclitaxel-cisplatin or fluorouracil-cisplatin with selective bladder preservation and adjuvant chemotherapy for patients with muscle invasive bladder cancer (RTOG 0233): a randomised multicentre phase 2 trial. Lancet Oncol. 2013 Aug;14(9):863-72. contains verified protocol link to PMC article PubMed
- Pooled Update: Efstathiou JA, Bae K, Shipley WU, Kaufman DS, Hagan MP, Heney NM, Sandler HM. Late pelvic toxicity after bladder-sparing therapy in patients with invasive bladder cancer: RTOG 89-03, 95-06, 97-06, 99-06. J Clin Oncol. 2009 Sep 1;27(25):4055-61. link to original article link to PMC article PubMed
- Pooled Update: Mak RH, Hunt D, Shipley WU, Efstathiou JA, Tester WJ, Hagan MP, Kaufman DS, Heney NM, Zietman AL. Long-Term Outcomes in Patients With Muscle-Invasive Bladder Cancer After Selective Bladder-Preserving Combined-Modality Therapy: A Pooled Analysis of Radiation Therapy Oncology Group Protocols 8802, 8903, 9506, 9706, 9906, and 0233. J Clin Oncol. 2014 Dec 1;32(34):3801-9. Epub 2014 Nov 3. link to original article contains verified protocol link to PMC article PubMed
Paclitaxel & RT
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Regimen
Study | Evidence |
Zapatero et al. 2012 | Non-randomized, <20 pts |
Preceding treatment
- Depending on response, treatment preceded by paclitaxel & RT induction or cystectomy.
Chemoradiotherapy
- Paclitaxel (Taxol) 50 mg/m2 IV once per week, given 6 hours before radiation therapy
- Concurrent radiation therapy according to one of the following:
- Accelerated hyperfractionated RT (AHFRT), 1.5 Gy fractions twice per day x 16 fractions (total consolidation dose: 24 Gy). After induction radiation therapy and consolidation radiation therapy, total dose to the bladder is 64.8 Gy; total dose to lymph nodes is 45.6 Gy.
- Normo-fractionated concurrent radiation therapy, total induction and consolidation dose of 64 to 66 Gy; Zapatero et al. 2012 did not specify how much of this dose was given during induction therapy vs. consolidation therapy.
References
- Zapatero A, Martin De Vidales C, Arellano R, Ibañez Y, Bocardo G, Perez M, Rabadan M, García Vicente F, Cruz Conde JA, Olivier C. Long-term results of two prospective bladder-sparing trimodality approaches for invasive bladder cancer: neoadjuvant chemotherapy and concurrent radio-chemotherapy. Urology. 2012 Nov;80(5):1056-62. Epub 2012 Sep 19. link to original article contains verified protocol PubMed
Adjuvant chemotherapy
Cisplatin & Gemcitabine
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Regimen
Study | Evidence |
Kaufman, et al. 2009 (RTOG 99-06) | Phase I/II |
Depanding on response to induction, treatment starts 12 weeks after cisplatin, paclitaxel, RT consolidation, or 8 weeks after cystectomy.
Chemotherapy
- Cisplatin (Platinol) 70 mg/m2 IV once on day 1
- Gemcitabine (Gemzar) 1000 mg/m2 IV once per day on days 1, 8, 15
28-day cycle for 4 cycles
References
- Kaufman DS, Winter KA, Shipley WU, Heney NM, Wallace HJ 3rd, Toonkel LM, Zietman AL, Tanguay S, Sandler HM. Phase I-II RTOG study (99-06) of patients with muscle-invasive bladder cancer undergoing transurethral surgery, paclitaxel, cisplatin, and twice-daily radiotherapy followed by selective bladder preservation or radical cystectomy and adjuvant chemotherapy. Urology. 2009 Apr;73(4):833-7. link to original article contains verified protocol PubMed
- Pooled Update: Efstathiou JA, Bae K, Shipley WU, Kaufman DS, Hagan MP, Heney NM, Sandler HM. Late pelvic toxicity after bladder-sparing therapy in patients with invasive bladder cancer: RTOG 89-03, 95-06, 97-06, 99-06. J Clin Oncol. 2009 Sep 1;27(25):4055-61. link to original article link to PMC article PubMed
- Pooled Update: Mak RH, Hunt D, Shipley WU, Efstathiou JA, Tester WJ, Hagan MP, Kaufman DS, Heney NM, Zietman AL. Long-Term Outcomes in Patients With Muscle-Invasive Bladder Cancer After Selective Bladder-Preserving Combined-Modality Therapy: A Pooled Analysis of Radiation Therapy Oncology Group Protocols 8802, 8903, 9506, 9706, 9906, and 0233. J Clin Oncol. 2014 Dec 1;32(34):3801-9. Epub 2014 Nov 3. link to original article contains verified protocol link to PMC article PubMed
MCV
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MCV: Methotrexate, Cisplatin, Vinblastine
Regimen
Study | Evidence |
Hagan, et al. 2003 (RTOG 97-06) | Phase I/II |
Begins 8 weeks after 2|cisplatin & RT consolidation. Not that only 45% of patients in RTOG 97-06 were able to complete all 3 cycles of MCV.
Chemotherapy
- Methotrexate (MTX) 30 mg/m2 IV once per day on days 1, 15, 22
- Cisplatin (Platinol) 25 mg/m2 IV once per day on days 2 to 4
- Vinblastine (Velban) 3 mg/m2 IV once per day on days 2, 15, 22
28-day cycle for 3 cycles
References
- 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
- Pooled Update: Efstathiou JA, Bae K, Shipley WU, Kaufman DS, Hagan MP, Heney NM, Sandler HM. Late pelvic toxicity after bladder-sparing therapy in patients with invasive bladder cancer: RTOG 89-03, 95-06, 97-06, 99-06. J Clin Oncol. 2009 Sep 1;27(25):4055-61. link to original article link to PMC article PubMed
- Pooled Update: Mak RH, Hunt D, Shipley WU, Efstathiou JA, Tester WJ, Hagan MP, Kaufman DS, Heney NM, Zietman AL. Long-Term Outcomes in Patients With Muscle-Invasive Bladder Cancer After Selective Bladder-Preserving Combined-Modality Therapy: A Pooled Analysis of Radiation Therapy Oncology Group Protocols 8802, 8903, 9506, 9706, 9906, and 0233. J Clin Oncol. 2014 Dec 1;32(34):3801-9. Epub 2014 Nov 3. link to original article contains verified protocol link to PMC article PubMed
Observation
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Regimen
Study | Evidence | Comparator | Efficacy |
Paz-Ares et al 2010 (SOGUG 99/01) | Phase III | PGC | Inferior OS |
Patients in SOGUG 99/01 had pT3-4 and/or pN positive disease with adequate renal function (CrCl greater than 50 mL/min/1.73m2). This arm underwent cystectomy and no further treatment. The study prematurely closed due to poor recruitment and lacks adequate power to make firm conclusions.
References
- Abstract: L. G. Paz-Ares, E. Solsona, E. Esteban, A. Saez, J. Gonzalez-Larriba, A. Anton, M. Hevia, F. de la Rosa, V. Guillem, and J. Bellmunt. Randomized phase III trial comparing adjuvant paclitaxel/gemcitabine/cisplatin (PGC) to observation in patients with resected invasive bladder cancer: Results of the Spanish Oncology Genitourinary Group (SOGUG) 99/01 study. ASCO MEETING ABSTRACTS Jun 22, 2010:LBA4518. link to abstract contains verified protocol
PGC
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PGC: Paclitaxel, Gemcitabine, Cisplatin
PCG: Paclitaxel, Cisplatin, Gemcitabine
Regimen #1
Study | Evidence | Comparator | Efficacy |
Paz-Ares et al 2010 (SOGUG 99/01) | Phase III | Observation | Superior OS |
Patients in SOGUG 99/01 had pT3-4 and/or pN positive disease with adequate renal function (CrCl greater than 50 mL/min/1.73m2). The study prematurely closed due to poor recruitment and lacks adequate power to make firm conclusions.
Patients initially underwent cystectomy; the median time treatment started post-cystectomy was 48 days.
Chemotherapy
- Paclitaxel (Taxol) 80 mg mg/2 IV oncer per day on days 1 & 8
- Gemcitabine (Gemzar) 1000 mg/m2 IV once per day on days 1 & 8
- Cisplatin (Platinol) 70 mg/m2 IV once on day 1
21-day cycle for 4 cycles
Regimen #2
Study | Evidence |
Mitin et al. 2013 (RTOG 02-33) | Non-randomized portion of RCT |
Depending on response, adjuvant chemotherapy began 12 weeks after cisplatin, paclitaxel, RT versus cisplatin, 5-FU, RT or 8 weeks after cystectomy.
Chemotherapy
- Cisplatin (Platinol) 35 mg/m2 IV once per day on days 1 & 8
- Gemcitabine (Gemzar) 1000 mg/m2 IV once per day on days 1 & 8
- Paclitaxel (Taxol) 50 mg/m2 IV once per day on days 1 & 8
21-day cycle for 4 cycles
References
- Abstract: L. G. Paz-Ares, E. Solsona, E. Esteban, A. Saez, J. Gonzalez-Larriba, A. Anton, M. Hevia, F. de la Rosa, V. Guillem, and J. Bellmunt. Randomized phase III trial comparing adjuvant paclitaxel/gemcitabine/cisplatin (PGC) to observation in patients with resected invasive bladder cancer: Results of the Spanish Oncology Genitourinary Group (SOGUG) 99/01 study. ASCO MEETING ABSTRACTS Jun 22, 2010:LBA4518. link to abstract contains verified protocol
- Mitin T, Hunt D, Shipley WU, Kaufman DS, Uzzo R, Wu CL, Buyyounouski MK, Sandler H, Zietman AL. Transurethral surgery and twice-daily radiation plus paclitaxel-cisplatin or fluorouracil-cisplatin with selective bladder preservation and adjuvant chemotherapy for patients with muscle invasive bladder cancer (RTOG 0233): a randomised multicentre phase 2 trial. Lancet Oncol. 2013 Aug;14(9):863-72. contains verified protocol link to PMC article PubMed
- Pooled Update: Efstathiou JA, Bae K, Shipley WU, Kaufman DS, Hagan MP, Heney NM, Sandler HM. Late pelvic toxicity after bladder-sparing therapy in patients with invasive bladder cancer: RTOG 89-03, 95-06, 97-06, 99-06. J Clin Oncol. 2009 Sep 1;27(25):4055-61. link to original article link to PMC article PubMed
- Pooled Update: Mak RH, Hunt D, Shipley WU, Efstathiou JA, Tester WJ, Hagan MP, Kaufman DS, Heney NM, Zietman AL. Long-Term Outcomes in Patients With Muscle-Invasive Bladder Cancer After Selective Bladder-Preserving Combined-Modality Therapy: A Pooled Analysis of Radiation Therapy Oncology Group Protocols 8802, 8903, 9506, 9706, 9906, and 0233. J Clin Oncol. 2014 Dec 1;32(34):3801-9. Epub 2014 Nov 3. link to original article contains verified protocol link to PMC article PubMed
Locally advanced or metastatic disease
Atezolizumab monotherapy
Atezolizumab (Tecentriq) for metastatic bladder cancer
Avelumab monotherapy
Avelumab (Bavencio) for metastatic bladder cancer
Carboplatin & Gemcitabine
Carboplatin & gemcitabine for unresectable or metastatic bladder cancer
Carboplatin & Paclitaxel
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Regimen
Study | Evidence | ORR | Pt Population |
Vaughn et al. 2002 (ECOG E2896) | Phase II | 24% (95% CI 12-42%) | Chemo-naive |
Chemotherapy
- Carboplatin (Paraplatin) AUC 6 IV once on day 1
- Paclitaxel (Taxol) 225 mg/m2 IV over 3 hours once on day 1
21-day cycle for up to 6 cycles
References
- Vaughn DJ, Manola J, Dreicer R, See W, Levitt R, Wilding G. Phase II study of paclitaxel plus carboplatin in patients with advanced carcinoma of the urothelium and renal dysfunction (E2896): a trial of the Eastern Cooperative Oncology Group. Cancer. 2002 Sep 1;95(5):1022-7. link to original article contains protocol PubMed
CISCA
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CISCA: CISplatin, Cyclophosphamide, Adriamycin (Doxorubicin)
Regimen
Study | Evidence | ORR | Comparator | Comparator ORR | Efficacy | Pt Population |
Logothetis et al. 1990 | Phase III | 46% (95% CI 32-62%) | MVAC | 65% (95% CI 52-77%) | Inferior OS | Chemo-naive |
Chemotherapy
- Cyclophosphamide (Cytoxan) 650 mg/m2 IV once on day 1
- Cisplatin (Platinol) 100 mg/m2 IV once on day 2
- Doxorubicin (Adriamycin) 50 mg/m2 IV once on day 2
Supportive medications
- Forced mannitol diuresis with Cisplatin (Platinol)
21-day cycle for up to 6 cycles
References
- Logothetis CJ, Dexeus FH, Finn L, Sella A, Amato RJ, Ayala AG, Kilbourn RG. A prospective randomized trial comparing MVAC and CISCA chemotherapy for patients with metastatic urothelial tumors. J Clin Oncol. 1990 Jun;8(6):1050-5. link to original article contains verified protocol PubMed
Cisplatin & Gemcitabine
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GC: Gemcitabine, Cisplatin
GP: Gemcitabine, Platinol (Cisplatin)
Regimen #1, 4-week schedule
Study | Evidence | Comparator | Efficacy |
von der Maase et al. 2000 | Phase III | MVAC | Seems not superior |
Soto Parra et al. 2002 | Randomized Phase II, <20 pts in this subgroup | Cisplatin & Gemcitabine, 3-week schedule, gemcitabine at 1000 mg/m2 | Not reported |
Bellmunt et al. 2012 (EORTC 30987) | Phase III | PCG | Might have inferior OS |
Only a minority of patients in Soto Parra et al. 2002 had bladder cancer. The majority of patients had non-small cell lung cancer.
Chemotherapy
- Cisplatin (Platinol) 70 mg/m2 IV over 30 to 60 minutes once on day 2
- Gemcitabine (Gemzar) 1000 mg/m2 IV over 30 to 60 minutes once per day on days 1, 8, 15
Supportive medications
- Per Soto Parra et al. 2002:
- 2 liters of fluid and "appropriate antiemetic therapy" given with cisplatin
- "blood-product transfusion and the administration of antibiotics, antiemetics and analgesics, as appropriate"
28-day cycle for up to 6 cycles, progression of disease, unacceptable toxicity, or physician discretion based on patient's best interests
Regimen #2, 3-week schedule, gemcitabine at 1250 mg/m2
Study | Evidence | ORR | Comparator | Comparator ORR | Efficacy | Pt Population |
Dogliotti et al. 2006 | Randomized Phase II | Intention to treat: 49% (95% CI NR) Evaluable patients only: 66% (95% CI: 49–80) |
Carboplatin & Gemcitabine | Intention to treat: 40% (95% CI NR) Evaluable patients only: 56% (95% CI: 40–72) |
Seems not superior | Chemo-naive |
Chemotherapy
- Cisplatin (Platinol) 70 mg/m2 IV once on day 2
- Gemcitabine (Gemzar) 1250 mg/m2 IV over 30 to 60 minutes once per day on days 1 & 8
21-day cycle for up to 6 cycles, until progression of disease, unacceptable toxicity, or physician discretion based on patient's best interests
Regimen #3, 3-week schedule, gemcitabine at 1000 mg/m2
Study | Evidence | Comparator | Efficacy | Pt Population |
Soto Parra et al. 2002 | Randomized Phase II, <20 pts in this subgroup | Cisplatin & Gemcitabine, 4-week schedule | Not reported | Chemo-naive |
Chemotherapy
- Cisplatin (Platinol) 70 mg/m2 IV over 30 to 60 minutes once on day 2
- Gemcitabine (Gemzar) 1000 mg/m2 IV once per day on days 1 & 8
Supportive medications
- 2 liters of fluid and "appropriate antiemetic therapy" given with Cisplatin (Platinol)
- "blood-product transfusion and the administration of antibiotics, antiemetics and analgesics, as appropriate"
21-day cycle for up to 6 cycles, progression of disease, unacceptable toxicity, or physician discretion based on patient's best interests
References
- von der Maase H, Hansen SW, Roberts JT, Dogliotti L, Oliver T, Moore MJ, Bodrogi I, Albers P, Knuth A, Lippert CM, Kerbrat P, Sanchez Rovira P, Wersall P, Cleall SP, Roychowdhury DF, Tomlin I, Visseren-Grul CM, Conte PF. Gemcitabine and cisplatin versus methotrexate, vinblastine, doxorubicin, and cisplatin in advanced or metastatic bladder cancer: results of a large, randomized, multinational, multicenter, phase III study. J Clin Oncol. 2000 Sep;18(17):3068-77. link to original article contains verified protocol PubMed
- Update: von der Maase H, Sengelov L, Roberts JT, Ricci S, Dogliotti L, Oliver T, Moore MJ, Zimmermann A, Arning M. Long-term survival results of a randomized trial comparing gemcitabine plus cisplatin, with methotrexate, vinblastine, doxorubicin, plus cisplatin in patients with bladder cancer. J Clin Oncol. 2005 Jul 20;23(21):4602-8. link to original article PubMed
- Soto Parra H, Cavina R, Latteri F, Sala A, Dambrosio M, Antonelli G, Morenghi E, Alloisio M, Ravasi G, Santoro A. Three-week versus four-week schedule of cisplatin and gemcitabine: results of a randomized phase II study. Ann Oncol. 2002 Jul;13(7):1080-6. link to original article contains verified protocol PubMed
- Dogliotti L, Cartenì G, Siena S, Bertetto O, Martoni A, Bono A, Amadori D, Onat H, Marini L. Gemcitabine plus cisplatin versus gemcitabine plus carboplatin as first-line chemotherapy in advanced transitional cell carcinoma of the urothelium: results of a randomized phase 2 trial. Eur Urol. 2007 Jul;52(1):134-41. Epub 2006 Dec 26. link to SD article contains verified protocol PubMed
- Bellmunt J, von der Maase H, Mead GM, Skoneczna I, De Santis M, Daugaard G, Boehle A, Chevreau C, Paz-Ares L, Laufman LR, Winquist E, Raghavan D, Marreaud S, Collette S, Sylvester R, de Wit R. Randomized Phase III Study Comparing Paclitaxel/Cisplatin/ Gemcitabine and Gemcitabine/Cisplatin in Patients With Locally Advanced or Metastatic Urothelial Cancer Without Prior Systemic Therapy: EORTC Intergroup Study 30987. J Clin Oncol. 2012 Apr 1;30(10):1107-13. Epub 2012 Feb 27. link to original article contains verified protocol link to PMC article PubMed
Docetaxel monotherapy
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Regimen
Study | Evidence | ORR | Comparator | Comparator ORR | Efficacy | Pt Population |
Choueiri et al. 2012 | Phase III | 11% (95% CI NR) | Docetaxel & Vandetanib | 7% (95% CI NR) | Seems not superior | Mix of chemo-naive and treated |
Bellmunt et al. 2017 (KEYNOTE-045) | Phase III | Pembrolizumab | Inferior OS | Second-line |
Chemotherapy
- Docetaxel (Taxotere) 75 mg/m2 IV on day 1
21-day cycles
References
- McCaffrey JA, Hilton S, Mazumdar M, Sadan S, Kelly WK, Scher HI, Bajorin DF. Phase II trial of docetaxel in patients with advanced or metastatic transitional-cell carcinoma. J Clin Oncol. 1997 May;15(5):1853-7. link to original article PubMed
- Choueiri TK, Ross RW, Jacobus S, Vaishampayan U, Yu EY, Quinn DI, Hahn NM, Hutson TE, Sonpavde G, Morrissey SC, Buckle GC, Kim WY, Petrylak DP, Ryan CW, Eisenberger MA, Mortazavi A, Bubley GJ, Taplin ME, Rosenberg JE, Kantoff PW. Double-blind, randomized trial of docetaxel plus vandetanib versus docetaxel plus placebo in platinum-pretreated metastatic urothelial cancer. J Clin Oncol. 2012 Feb 10;30(5):507-12. link to original article link to PMC article PubMed
- Bellmunt J, de Wit R, Vaughn DJ, Fradet Y, Lee JL, Fong L, Vogelzang NJ, Climent MA, Petrylak DP, Choueiri TK, Necchi A, Gerritsen W, Gurney H, Quinn DI, Culine S, Sternberg CN, Mai Y, Poehlein CH, Perini RF, Bajorin DF; KEYNOTE-045 Investigators. Pembrolizumab as Second-Line Therapy for Advanced Urothelial Carcinoma. N Engl J Med. 2017 Mar 16;376(11):1015-1026. Epub 2017 Feb 17. link to original article contains verified protocol PubMed
Durvalumab monotherapy
Durvalumab (Imfinzi) for metastatic bladder cancer
Gemcitabine & Paclitaxel
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Regimen #1
Study | Evidence | ORR | Pt Population |
Calabrò et al. 2009 | Phase II | 37% | untreated |
Chemotherapy
- Gemcitabine (Gemzar) 2500 mg/m2 IV over 30 minutes once on day 1, given second
- Paclitaxel (Taxol) 150 mg/m2 IV over 3 hours once on day 1, given first
14-day cycle for 6 to 12 cycles
Regimen #2
Study | Evidence | ORR | Pt Population |
Meluch et al. 2001 | Phase II | 54% (95% CI 40-67%) | mix of chemo-naive and exposed (but not with gemcitabine or paclitaxel) |
Chemotherapy
- Gemcitabine (Gemzar) 1000 mg/m2 IV once per day on days 1, 8, 15
- Paclitaxel (Taxol) 200 mg/m2 IV over 3 hours once on day 1
21-day cycle for up to 6 cycles
References
- Meluch AA, Greco FA, Burris HA 3rd, O'Rourke T, Ortega G, Steis RG, Morrissey LH, Johnson V, Hainsworth JD. Paclitaxel and gemcitabine chemotherapy for advanced transitional-cell carcinoma of the urothelial tract: a phase II trial of the Minnie pearl cancer research network. J Clin Oncol. 2001 Jun 15;19(12):3018-24. link to original article PubMed
- Calabrò F, Lorusso V, Rosati G, Manzione L, Frassineti L, Sava T, Di Paula ED, Alonso S, Sternberg CN. Gemcitabine and paclitaxel every 2 weeks in patients with previously untreated urothelial carcinoma. Cancer. 2009 Jun 15;115(12):2652-9. link to original article contains verified protocol PubMed
MVAC
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MVAC: Methotrexate, Vinblastine, Adriamycin, Cisplatin
Regimen #1, dose-dense
Study | Evidence | ORR | Comparator | Comparator ORR | Efficacy | Pt Population |
Sternberg et al. 2001 (EORTC 30924) | Phase III | 62% (95% CI 54-70%) | Standard MVAC | 50% (95% CI 42-59%) | Seems to have superior PFS | Chemo-naive |
Chemotherapy
- Methotrexate (MTX) 30 mg/m2 IV once on day 1
- Vinblastine (Velban) 3 mg/m2 IV once on day 2
- Doxorubicin (Adriamycin) 30 mg/m2 IV once on day 2
- Cisplatin (Platinol) 70 mg/m2 IV once on day 2
Supportive medications
- G-CSF 240 mcg/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 greater than 30,000/uL.
- In contrast to Sternberg et al. 2001, Sternberg et al. 2006 said G-CSF was given on days 3 to 7.
14-day cycles, given until progression of disease or unacceptable toxicity
In contrast to Sternberg et al. 2001, Sternberg et al. 2006 specified 15-day cycles
Regimen #2, standard
Study | Evidence | Comparator | Efficacy |
Logothetis et al. 1990 | Phase III | CISCA | Superior OS |
von der Maase et al. 2000 | Phase III | Cisplatin & Gemcitabine | Seems not superior |
Sternberg et al. 2001 (EORTC 30924) | Phase III | Dose-dense MVAC | Seems to have inferior PFS |
Han et al. 2008 | Phase II |
Chemotherapy
- Methotrexate (MTX) 30 mg/m2 IV once per day on days 1, 15, 22
- Vinblastine (Velban) 3 mg/m2 IV once per day on days 2, 15, 22
- Doxorubicin (Adriamycin) 30 mg/m2 IV once on day 2
- Cisplatin (Platinol) 70 mg/m2 IV once on day 2
28-day cycles (number of cycles and criteria to continue therapy varies depending on reference)
References
- Logothetis CJ, Dexeus FH, Finn L, Sella A, Amato RJ, Ayala AG, Kilbourn RG. A prospective randomized trial comparing MVAC and CISCA chemotherapy for patients with metastatic urothelial tumors. J Clin Oncol. 1990 Jun;8(6):1050-5. link to original article contains verified protocol PubMed
- von der Maase H, Hansen SW, Roberts JT, Dogliotti L, Oliver T, Moore MJ, Bodrogi I, Albers P, Knuth A, Lippert CM, Kerbrat P, Sanchez Rovira P, Wersall P, Cleall SP, Roychowdhury DF, Tomlin I, Visseren-Grul CM, Conte PF. Gemcitabine and cisplatin versus methotrexate, vinblastine, doxorubicin, and cisplatin in advanced or metastatic bladder cancer: results of a large, randomized, multinational, multicenter, phase III study. J Clin Oncol. 2000 Sep;18(17):3068-77. link to original article contains verified protocol PubMed
- Update: von der Maase H, Sengelov L, Roberts JT, Ricci S, Dogliotti L, Oliver T, Moore MJ, Zimmermann A, Arning M. Long-term survival results of a randomized trial comparing gemcitabine plus cisplatin, with methotrexate, vinblastine, doxorubicin, plus cisplatin in patients with bladder cancer. J Clin Oncol. 2005 Jul 20;23(21):4602-8. link to original article 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
- Update: Sternberg CN, de Mulder P, Schornagel JH, Theodore C, Fossa SD, van Oosterom AT, Witjes JA, Spina M, van Groeningen CJ, Duclos B, Roberts JT, de Balincourt C, Collette L; EORTC Genito-Urinary Cancer Group. Seven year update of an EORTC phase III trial of high-dose intensity M-VAC chemotherapy and G-CSF versus classic M-VAC in advanced urothelial tract tumours. Eur J Cancer. 2006 Jan;42(1):50-4. Epub 2005 Dec 5. link to SD article contains verified protocol PubMed
- Han KS, Joung JY, Kim TS, Jeong IG, Seo HK, Chung J, Lee KH. Methotrexate, vinblastine, doxorubicin and cisplatin combination regimen as salvage chemotherapy for patients with advanced or metastatic transitional cell carcinoma after failure of gemcitabine and cisplatin chemotherapy. Br J Cancer. 2008 Jan 15;98(1):86-90. Epub 2007 Dec 18. link to original article contains verified protocol link to PMC article PubMed
Nivolumab monotherapy
Nivolumab (Opdivo) for unresectable or metastatic bladder cancer
Paclitaxel monotherapy
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Regimen, q3wks
Study | Evidence | Comparator | Efficacy | Pt Population |
Bellmunt et al. 2017 (KEYNOTE-045) | Phase III | Pembrolizumab | Inferior OS | Second-line |
Chemotherapy
- Paclitaxel (Taxol) 175 mg/m2 IV once on day 1
21-day cycles
Regimen #2, 3 out of 4 weeks
Study | Evidence | ORR | Pt Population |
Vaughn et al. 2002 | Phase II | 10% (95% CI 0-20%) | One prior regimen |
Chemotherapy
- Paclitaxel (Taxol) 175 mg/m2 IV over 60 minutes once per day on days 1, 8, 15
28-day cycles
References
- Vaughn DJ, Broome CM, Hussain M, Gutheil JC, Markowitz AB. Phase II trial of weekly paclitaxel in patients with previously treated advanced urothelial cancer. J Clin Oncol. 2002 Feb 15;20(4):937-40. link to original article contains protocol PubMed
- Bellmunt J, de Wit R, Vaughn DJ, Fradet Y, Lee JL, Fong L, Vogelzang NJ, Climent MA, Petrylak DP, Choueiri TK, Necchi A, Gerritsen W, Gurney H, Quinn DI, Culine S, Sternberg CN, Mai Y, Poehlein CH, Perini RF, Bajorin DF; KEYNOTE-045 Investigators. Pembrolizumab as Second-Line Therapy for Advanced Urothelial Carcinoma. N Engl J Med. 2017 Mar 16;376(11):1015-1026. Epub 2017 Feb 17. link to original article contains verified protocol PubMed
Paclitaxel, nanoparticle albumin-bound monotherapy
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Regimen
Study | Evidence | ORR | Pt Population |
Ko et al. 2013 | Phase II | 28% (95% CI 17-44%) | One prior platinum regimen |
Chemotherapy
- Paclitaxel, nanoparticle albumin-bound (Abraxane) 260 mg/m2 IV on day 1
21-day cycles
Dose modifications
- "Two dose reductions were permitted, to 240 mg/m2 and then to 180 mg/m2. When further dose reductions were required, study treatment was discontinued. Patients with febrile neutropenia, or delay of cycle because of persistent neutropenia, ANC of less than 500/uL for 1 week, or grade 3 or 4 thrombocytopenia required dose reductions. When sensory neuropathy of grade 2 or higher occurred, study drug was withheld until resolution to grade 2 or better, then reinstituted at the next lower dose. When mucositis or diarrhea of grade 3 or higher occurred, study drug was withheld until resolution to grade 1 or better, then reinstituted at the next lower dose. Patients with mucositis or diarrhea of grade 4 were removed from the trial."
References
- Ko YJ, Canil CM, Mukherjee SD, Winquist E, Elser C, Eisen A, Reaume MN, Zhang L, Sridhar SS. Nanoparticle albumin-bound paclitaxel for second-line treatment of metastatic urothelial carcinoma: a single group, multicentre, phase 2 study. Lancet Oncol. 2013 Jul;14(8):769-76. link to original article contains protocol PubMed
PGC
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PGC: Paclitaxel, Gemcitabine, Cisplatin
PCG: Paclitaxel, Cisplatin, Gemcitabine
Regimen
Study | Evidence | ORR | Comparator | Comparator ORR | Efficacy | Pt Population |
Bellmunt et al. 2012 (EORTC 30987) | Phase III | 56% (95% CI NR) | Cisplatin & Gemcitabine | 44% (95% CI NR) | Might have superior OS | Chemo-naive |
Chemotherapy
- Cisplatin (Platinol) 70 mg/m2 IV once on day 1
- Gemcitabine (Gemzar) 1000 mg/m2 IV over 30 to 60 minutes once per day on days 1 & 8
- Paclitaxel (Taxol) 80 mg/m2 IV once per day on days 1 & 8, given first
21-day cycle for up to 6 cycles
References
- Bellmunt J, von der Maase H, Mead GM, Skoneczna I, De Santis M, Daugaard G, Boehle A, Chevreau C, Paz-Ares L, Laufman LR, Winquist E, Raghavan D, Marreaud S, Collette S, Sylvester R, de Wit R. Randomized Phase III Study Comparing Paclitaxel/Cisplatin/ Gemcitabine and Gemcitabine/Cisplatin in Patients With Locally Advanced or Metastatic Urothelial Cancer Without Prior Systemic Therapy: EORTC Intergroup Study 30987. J Clin Oncol. 2012 Apr 1;30(10):1107-13. Epub 2012 Feb 27. link to original article contains verified protocol link to PMC article PubMed
Pembrolizumab monotherapy
Pembrolizumab (Keytruda) for unresectable or metastatic bladder cancer
Pemetrexed monotherapy
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Regimen
Study | Evidence | ORR | Pt Population |
Sweeney, et al. 2006 | Phase II | 28% (95% CI 16-43%) | One prior regimen |
Chemotherapy
- Pemetrexed (Alimta) 500 mg/m2 IV over 10 minutes once on day 1
21-day cycles
References
- Sweeney CJ, Roth BJ, Kabbinavar FF, Vaughn DJ, Arning M, Curiel RE, Obasaju CK, Wang Y, Nicol SJ, Kaufman DS. Phase II study of pemetrexed for second-line treatment of transitional cell cancer of the urothelium. J Clin Oncol. 2006 Jul 20;24(21):3451-7. link to original article contains protocol PubMed
Links
- EORTC Risk Tables for Predicting Recurrence and Progression in Individual Patients with Stage Ta T1 Bladder Cancer - predicts probability of recurrence and progression in 1 to 5 years
Urine assays
These are assays intended/being investigated as adjuncts to urine cytology and cystoscopy.
- Cxbladder (uRNA-2), a "urine based bladder cancer test (uRNA-2) which detects RNA markers in urine."
- ImmunoCyt™/uCyt+™, a cell-based detection assay which "uses fluorescent-labeled antibodies to 3 markers that are commonly found on malignant exfoliated urothelial cells."[1]
- UroVysion (Abbott Molecular) "designed to detect aneuploidy for chromosomes 3, 7, 17, and loss of the 9p21 locus via fluorescence in situ hybridization (FISH) in urine specimens from persons with hematuria suspected of having bladder cancer."
References
- ↑ Greene KL, Berry A, Konety BR. Diagnostic Utility of the ImmunoCyt/uCyt+ Test in Bladder Cancer. Rev Urol. 2006 Fall;8(4):190-7. link to PMC article PubMed