A multicentre phase II study of hypofractionated conformal radiotherapy with concurrent gemcitabine in muscle-invasive bla...
Outline <ul><li>Background </li></ul><ul><li>Results of phase II GemX study </li></ul><ul><li>Future directions </li></ul>
Introduction <ul><li>Radical treatment for MIBC can be radiotherapy or surgery </li></ul><ul><li>Survival is ~50% at 5 yea...
Comparison of RT and surgery: Disease-specific survival Kotwal et al: Int. J. Radiation Oncology Biol. Phys., Vol. 70, No....
Prognostic factors <ul><li>Age/performance status </li></ul><ul><li>Stage </li></ul><ul><li>Renal function </li></ul><ul><...
Patient selection for radical radiotherapy treatment <ul><li>Localised-disease muscle-invasive cancer </li></ul><ul><li>Ma...
Conventional whole bladder RT-The Christie 1 <ul><li>Maximal TURBT </li></ul><ul><li>Staged using MRI pelvis and CXR </li>...
Christie series Cowan. R, McBain. C. et al. Int. J. Radiation Oncology Biol. Phys., Vol. 59, pp. 197-207, 2004 5yr Surviva...
Chemoradiation <ul><li>Chemoradiation increases the rate of bladder preservation and local control compared to radiotherap...
Results of Canadian Trial Pelvic-recurrence free survival Overall survival Coppin et al: Journal of Clinical Oncology, Vol...
Summary of bladder preservation studies to 2010 Rene et al.  Curr Oncol > v.16(4); Aug 2009
Rationale for GemX <ul><li>Gemcitabine is effective in bladder cancer and is a potent radiosensitizer  in vitro  (1). </li...
Christie phase I GemX study <ul><li>3+3 design </li></ul><ul><li>8 patients </li></ul><ul><li>T2=4, T3=4 </li></ul><ul><li...
Phase II methods <ul><li>Phase II study </li></ul><ul><li>T2/3 N0 M0 bladder cancer </li></ul><ul><li>PS 0-2 </li></ul><ul...
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 ...
Treatment <ul><li>All patients completed RT </li></ul><ul><li>46 patients completed 4 cycles of Gem </li></ul><ul><li>2 pa...
Check cystoscopy <ul><li>Median time from start of RT: </li></ul><ul><li>135 days (72-248 days) </li></ul>GemX Standard RT...
Outcomes <ul><li>Median follow up: 36 months (15-61 months) </li></ul><ul><li>2 intercurrent deaths within 90 days of trea...
Cystectomy post GemX <ul><li>4 cystectomies post RT: </li></ul><ul><li>8 months, 17 months, 30 months, 45 months </li></ul...
Survival <ul><li>Survival calculated from start of RT </li></ul><ul><li>Overall survival and disease-specific survival det...
Overall survival <ul><li>3yr overall survival: 75%;  5yr OS: 65%  </li></ul><ul><li>Conventional RT:  3yr overall survival...
Disease-specific survival <ul><li>3yr disease-specific survival: 82%; 5yr DSC: 78% </li></ul><ul><li>Conventional RT: 5yr ...
Patient-reported late toxicity
Bladder preservation 2011 <ul><li>BC2001: 360 pts RT v CRT: reported in abstract form </li></ul><ul><li>BCON: 333 pts RT v...
Cause-specific survival of patients with primary v secondary cystectomy Addla et al. The Journal of Urology Vol. 181, Issu...
Where do we go from here? <ul><li>Lower T3/hydronephrosis incidence may reflect more recent surgical policy of treating po...
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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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A multicentre phase II study of hypofractionated conformal radiotherapy with concurrent gemcitabine in muscle-invasive bladder cancer

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

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