Urothelial carcinoma

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Neoadjuvant chemotherapy

CMV

CMV: Cisplatin, Methotrexate, Vinblastine

Regimen

• Methotrexate (MTX) 30 mg/m2 IV bolus on days 1 & 8
• Vinblastine (Velban) 4 mg/m2 IV bolus on days 1 & 8
• Cisplatin (Platinol) 100 mg/m2 IV on day 2, before hydration
• Folinic acid (Leucovorin) 15 mg PO/IV every 6 hours x 4 doses 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

1. 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

• Methotrexate (MTX) 30 mg/m2 IV on days 1, 15, 22
• Vinblastine (Velban) 3 mg/m2 IV on days 2, 15, 22
• Doxorubicin (Adriamycin) 30 mg/m2 IV on day 2
• Cisplatin (Platinol) 70 mg/m2 IV on day 2

28-day cycles x 3 cycles

References

1. Grossman HB, Natale RB, Tangen CM, Speights VO, Vogelzang NJ, Trump DL, deVere White RW, Sarosdy MF, Wood DP Jr, Raghavan D, Crawford ED. Neoadjuvant chemotherapy plus cystectomy compared with cystectomy alone for locally advanced bladder cancer. N Engl J Med. 2003 Aug 28;349(9):859-66. link to original article PubMed

Concurrent chemotherapy & radiation

Cisplatin & RT

Regimen

• Cisplatin (Platinol) 100 mg/m2 IV on days 1 & 22
• Concurrent radiation therapy, total of 39.6 Gy

• If patient is not in complete remission, proceed to cystectomy.
• If patient is in compete remission, treat with an additional:
  • Cisplatin (Platinol) 100 mg/m2 IV on day 1
  • Concurrent radiation therapy, 25.2 Gy (cumulative dose of 64.8 Gy)

References

1. Shipley WU, Winter KA, Kaufman DS, Lee WR, Heney NM, Tester WR, Donnelly BJ, Venner PM, Perez CA, Murray KJ, Doggett RS, True LD. Phase III trial of neoadjuvant chemotherapy in patients with invasive bladder cancer treated with selective bladder preservation by combined radiation therapy and chemotherapy: initial results of Radiation Therapy Oncology Group 89-03. J Clin Oncol. 1998 Nov;16(11):3576-83. link to original article PubMed

Chemotherapy for metastatic disease

MVAC

MVAC: Methotrexate, Vinblastine, Adriamycin, Cisplatin

Regimen

• Methotrexate (MTX) 30 mg/m2 IV on days 1, 15, 22
• Vinblastine (Velban) 3 mg/m2 IV on days 2, 15, 22
• Doxorubicin (Adriamycin) 30 mg/m2 IV on day 2
• Cisplatin (Platinol) 70 mg/m2 IV on day 2

28-day cycles x 6 cycles

References

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

Carboplatin (Paraplatin) & Paclitaxel (Taxol)

Regimen

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

21-day cycles x up to 6 cycles

References

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

Cisplatin (Platinol) & Gemcitabine (Gemzar)

Regimen

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

28-day cycles x 6 cycles

References

1. von der Maase H, Hansen SW, Roberts JT, Dogliotti L, Oliver T, Moore MJ, Bodrogi I, Albers P, Knuth A, Lippert CM, Kerbrat P, Sanchez Rovira P, Wersall P, Cleall SP, Roychowdhury DF, Tomlin I, Visseren-Grul CM, Conte PF. Gemcitabine and cisplatin versus methotrexate, vinblastine, doxorubicin, and cisplatin in advanced or metastatic bladder cancer: results of a large, randomized, multinational, multicenter, phase III study. J Clin Oncol. 2000 Sep;18(17):3068-77. link to original article PubMed

Cisplatin (Platinol), Gemcitabine (Gemzar), Paclitaxel (Taxol)

Regimen

• Cisplatin (Platinol) 70 mg/m2 IV on day 1
• Gemcitabine (Gemzar) 1000 mg/m2 IV over 30-60 minutes on days 1 & 8
• Paclitaxel (Taxol) 80 mg/m2 IV on days 1 & 8

21-day cycles x up to 6 cycles

References

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

Gemcitabine (Gemzar) & Paclitaxel (Taxol)

Regimen

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

21-day cycles x up to 6 cycles

References

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

Pemetrexed (Alimta)

Regimen

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

21-day cycles

References

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