A multicentre phase II study of hypofractionated conformal radiotherapy with concurrent gemcitabine in muscle-invasive bladder cancer
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A multicentre phase II study of hypofractionated conformal radiotherapy with concurrent gemcitabine in muscle-invasive bladder cancer

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This presentation forms a part of a Virtual Edition on Radiotherapy for bladder cancer

This presentation forms a part of a Virtual Edition on Radiotherapy for bladder cancer
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A multicentre phase II study of hypofractionated conformal radiotherapy with concurrent gemcitabine in muscle-invasive bladder cancer A multicentre phase II study of hypofractionated conformal radiotherapy with concurrent gemcitabine in muscle-invasive bladder cancer Presentation Transcript

  • A multicentre phase II study of hypofractionated conformal radiotherapy with concurrent gemcitabine in muscle-invasive bladder cancer A. Choudhury*, R. Swindell*, J. P. Logue*, P. A. Elliott*, J.E. Livsey*, P. Symonds # , J. P. Wylie*, N.W. Clarke*, A. E. Kiltie $ , R.A. Cowan* *The Christie, Wimslow Road, Manchester M20 4BX, # Leicester Royal Infirmary, Leicester LE1 5WW, $ The Gray Institute, Oxford OX3 7DQ J Clin Oncol. 2011 Feb 20;29(6):733-8. Epub 2011 Jan 4.
  • Outline
    • Background
    • Results of phase II GemX study
    • Future directions
  • Introduction
    • Radical treatment for MIBC can be radiotherapy or surgery
    • Survival is ~50% at 5 years for either modality
    • .
  • Comparison of RT and surgery: Disease-specific survival Kotwal et al: Int. J. Radiation Oncology Biol. Phys., Vol. 70, No. 2, pp. 456–463, 2008
  • Prognostic factors
    • Age/performance status
    • Stage
    • Renal function
    • Hydronephrosis
    • Unifocal disease – no widespread CIS
  • Patient selection for radical radiotherapy treatment
    • Localised-disease muscle-invasive cancer
    • Maximal Trans-Urethral Resection of Bladder
    • Good bladder function
    • WHO PS ≤3
  • Conventional whole bladder RT-The Christie 1
    • Maximal TURBT
    • Staged using MRI pelvis and CXR
    • Whole Bladder RT: 52.5 Gy/20#
    • n=60
    (1) Cowan et al. Int. J. Radiation Oncology Biol. Phys., Vol. 59, No. 1, pp. 197–207, 2004
  • Christie series Cowan. R, McBain. C. et al. Int. J. Radiation Oncology Biol. Phys., Vol. 59, pp. 197-207, 2004 5yr Survival OS: 58% DSS: 65%
  • Chemoradiation
    • Chemoradiation increases the rate of bladder preservation and local control compared to radiotherapy alone
    • Effect on survival is unclear, although no detriment
    • The optimal chemotherapy regimen is unknown
  • Results of Canadian Trial Pelvic-recurrence free survival Overall survival Coppin et al: Journal of Clinical Oncology, Vol 14, No 11 (November), 1996: pp 2901-2907
  • Summary of bladder preservation studies to 2010 Rene et al. Curr Oncol > v.16(4); Aug 2009
  • Rationale for GemX
    • Gemcitabine is effective in bladder cancer and is a potent radiosensitizer in vitro (1).
    • Christie phase I study found acceptable toxicity when combined with hypofractionation (2)
    • Sangar et al. Br J Cancer. 2004 Jan 26;90(2):542-8.
    • Sangar et al. Int. J. Radiation Oncology Biol. Phys., Vol. 61, No. 2, pp. 420–425, 2005
  • Christie phase I GemX study
    • 3+3 design
    • 8 patients
    • T2=4, T3=4
    • Dose-limiting toxicity grade 3+ (RTOG)
    • All 8 completed RT
    • 6/8 completed chemoradiotherapy
    • G3 toxicity at 150mg/m 2
    • 100mg/m 2 taken forward to phase II
    Sangar et al: Int J Radiat Oncol Biol Phys. 2005 Feb 1;61(2):420-5.
  • Phase II methods
    • Phase II study
    • T2/3 N0 M0 bladder cancer
    • PS 0-2
    • 52.5 Gy/20#: CT and conformal planning
    • Gem 100mg/m 2 weekly during RT
    • Median FUp: 36 months (16-62 months)
    Choudhury et al. J Clin Oncol. 2011 Feb 20;29(6):733-8. Epub 2011 Jan 4.
  • Centres Manchester 31 Leeds 10 Preston 2 Leicester 7
  • Preliminary results compared to conventional Age Median 67yrs (48-84yrs) Median 67yrs (40-82yrs) Gender M: 39 F: 11 M: 44 F: 16 WHO PS 0: 25 1: 19 2: 1 Not known: 5 ≤ 1: 53 >1: 7 Histology TCC: 47 Mixed: 3 TCC: 55 Grade II: 3 III: 47 II: 8 III: 51 CIS 12 T stage T2: 40 T3: 8 T2: 17 T3: 42 Hydronephrosis 5 18
  • Treatment
    • All patients completed RT
    • 46 patients completed 4 cycles of Gem
    • 2 patients had 2 courses and 2 patients had 3 courses – all four stopped due to G3 GI toxicity.
  • Check cystoscopy
    • Median time from start of RT:
    • 135 days (72-248 days)
    GemX Standard RT CR 44 88% 45 75% Superficial 3 6% 7 12% Muscle-invasive 0 3 4% Not done 3 6% 5 8%
  • Outcomes
    • Median follow up: 36 months (15-61 months)
    • 2 intercurrent deaths within 90 days of treatment (one MI and one pneumonia)
    • 7 deaths from disease
    • 5 intercurrent deaths
    • 36 currently alive: 2 with metastatic disease and 5 with local superficial disease
  • Cystectomy post GemX
    • 4 cystectomies post RT:
    • 8 months, 17 months, 30 months, 45 months
    • Three due to recurrent disease and one due to toxicity
    • One patient had a bowel resection only due to late toxicity.
  • Survival
    • Survival calculated from start of RT
    • Overall survival and disease-specific survival determined.
    • 32 alive with an intact bladder
  • Overall survival
    • 3yr overall survival: 75%; 5yr OS: 65%
    • Conventional RT: 3yr overall survival: 65%; 5yr OS: 58%
  • Disease-specific survival
    • 3yr disease-specific survival: 82%; 5yr DSC: 78%
    • Conventional RT: 5yr disease-specific survival: 65%
  • Patient-reported late toxicity
  • Bladder preservation 2011
    • BC2001: 360 pts RT v CRT: reported in abstract form
    • BCON: 333 pts RT v RT+CN: ↑13% OS @ 3yrs (p=0.04)
  • Cause-specific survival of patients with primary v secondary cystectomy Addla et al. The Journal of Urology Vol. 181, Issue 4, Supplement, Page 633
  • Where do we go from here?
    • Lower T3/hydronephrosis incidence may reflect more recent surgical policy of treating poor prognosis patients?
    • Where does GemX fit in?
    • Role of neoadjuvant chemotherapy?
    • Now giving neoadjuvant Gem/Cis with GemX and collecting toxicity data