Adjuvant therapy: – Additional cancer treatment given after the primary treatment to lower the risk that the cancer will come back Neo-adjuvant therapy:

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  • Adjuvant therapy:Additional cancer treatment given after the primary treatment to lower the risk that the cancer will come back

    Neo-adjuvant therapy:Treatment given as a first step to shrink a tumor before the main treatment, which is usually surgery, is givenNCI Dictionary of Cancer Terms

  • Presentation at diagnosis1:45% with localized disease25% with locally advanced disease2030% metastatic disease33% of patients treated for localized disease will develop metastatic disease21. National Cancer Institute. SEER cancer statistics fact sheet: cancer of the kidney and renal pelvis. Accessed 2009;2. Flanigan RC et al. Curr Treat Options Oncol 2003;4:38590.

  • Closed adjuvant trialsNAuthor (year)Outcome of the studyRT vs. observation72Kjaer (1987)negativeMPA vs. observation136Pizzocaro (1987)negativeAut. tumor vaccine + BCG vs. observation43Adler (1987)negativeAut. tumor vaccine BCG vs. observation120Galligioni (1996)negativeUFT vs. observation71Naito (1997)negativeIFN- vs. observation247Pizzocaro (2001)negativeIFN- NL vs. observation283Messing (2003)negativeHD IL-2 vs. observation69Clark (2003)negativeAutologous tumor vaccine vs. observation553Jocham (2004)positive in terms of PFS (p=0.02)s.c. IL-2 + IFN- + 5-FU vs. observation203Atzpodien (2005)negatives.c. IL-2 + IFN- vs. observation310Passalacqua (2007)negativeAut. tumour-derived HSP-96-peptide complexvs. observation918Wood C (2008)negativeThalidomide vs. observation46*Margulis (2009)negative*trial stopped due to inefficacys.c. IL-2 + IFN- + 5-FU vs. observation550Aitchinson (2012)negativeGirentuximab (anti-CAIX MoAb) vs. observation856Belldegrun (2013)negative

  • Closed adjuvant trialsNAuthor (year)Outcome of the studyRT vs. observation72Kjaer (1987)negativeMPA vs. observation136Pizzocaro (1987)negativeAut. tumor vaccine + BCG vs. observation43Adler (1987)negativeAut. tumor vaccine BCG vs. observation120Galligioni (1996)negativeUFT vs. observation71Naito (1997)negativeIFN- vs. observation247Pizzocaro (2001)negativeIFN- NL vs. observation283Messing (2003)negativeHD IL-2 vs. observation69Clark (2003)negativeAutologous tumor vaccine vs. observation553Jocham (2004)positive in terms of PFS (p=0.02)s.c. IL-2 + IFN- + 5-FU vs. observation203Atzpodien (2005)negatives.c. IL-2 + IFN- vs. observation310Passalacqua (2007)negativeAut. tumour-derived HSP-96-peptide complexvs. observation918Wood C (2008)negativeThalidomide vs. observation46*Margulis (2009)negative*trial stopped due to inefficacys.c. IL-2 + IFN- + 5-FU vs. observation550Aitchinson (2012)negativeGirentuximab (anti-CAIX MoAb) vs. observation856Belldegrun (2013)negative

  • Massari F, et al. Clin Genitourin Cancer 2013 (E-pub ahead of print)

  • Ongoing adjuvant trialsSORCE (MRC/EORTC)Sorafenib 1 year (+ 2 years placebo) vs. Sorafenib 3 years vs. placebo 3 years1656Leibovich score of 3 to 8.Primary end-point: DFSClosed at enrolment;no data available yetASSURE (ECOG)Sunitinib 1 year vs. Sorafenib 1 year vs. placebo 1 year1923T3b-4 N0, T1-4 N+, or T1-4 with positive margins or vascular invasion)Primary end-point: DFSClosed at enrolment;no data available yetS-TRAC (Pfizer)Sunitinib 1 year vs. placebo 1 year856High risk according to UISS.Primary end-point: DFSClosed at enrolment;no data available yetEVEREST (SWOG)Everolimus vs. placebo (days 1-42; treatment repeats every 6 weeks for 9 courses)1218Pathologically intermediate high-risk or very high-risk.Primary end-point: DFSNot yet enrolling(US only)

    VEG113387 PROTECT study (GSK)Pazopanib 1 year vs. placebo 1 year1500Intermediate and high risk.Primary end-point: DFSClosed at enrolment;no data available yet

    NCT01599754 (SFJ Pharmaceuticals)Axitinib 3 yeas vs. placebo 3 years592pT2 or higher, pNx pN0 or pN1, M0, Fuhrman G3-4 and ECOG PS 0-1Primary end-point: DFSEnrolling(Japan only)

  • To date, no treatment emerged as a standard of care in this setting

    Presently, patients should be thus offered just obser-vation

    Enrollment into well-desigend and adequately con-ducted RCTs is mandatory

  • ProConsLitmus test for patients who will do well

    Therapy may impact wound healing and recoveryPotential for higher incidence of wound complicationsIncorporates cytoreductive surgery to examine tissue before and after therapy for endpoint targetsLocal tumor progression in non-responders increases complexity of the surgeryMore ectomies= Worse outcomeMay see responses in the primary tumor not seen beforeTiming is everythingWhy interrupt a therapeutic response?Who wants to operate on therapy refractory disease?Eliminates unnecessary and morbid surgery in patients who dont respond

  • Escudier B, et al. ECCO 13 the European Cancer Conference, Paris, October 30-November 3, 2005; abs.794.Sorafenib treatment

  • Shuch B, et al. BJU Int 2008;102:692-696Level II thrombusLevel I thrombusSunitinib treatment(4 cycles)

  • Jonasch E, et al. J Clin Oncol 2009;27:4076-81Baseline8 Weeks of therapyBevacizumab treatment

  • Van der Veldt AAM, et al. Clin Cancer Res 2008;14:2431-6; Thomas AA, et al. J Urol 2009;181:518-23;Jonasch E, et al. J Clin Oncol 2009;27:4076-81

    Primary Tumor Regressionn=45 (%)>20% growth 1 (2)10-20% growth 2 (4)0-10% growth 19 (42)1-10% shrinkage 13 (29)11-20% shrinkage 7 (16)20-30% shrinkage 3 (7)

  • CG Wood, personal communication

  • CG Wood, personal communication

    Pre-Surgical TherapyImmediate SurgeryTotalp Overall25 (43.1)28 (28.7)54 (33.5)0.048 Peri-operative Death1 (1.7)2 (2.0)3 (1.9)0.91 Readmission to Hospital6 (10.3)11 (11.0)17 (10.8)0.90 Bleeding1 (1.7)2 (2.0)3 (1.9)0.91 Thromboembolic5 (8.6)5 (5.0)10 (6.3)0.36 Cardiac1 (1.7)3 (3.0)4 (2.5)0.63 Gastrointestinal5 (8.6)9 (8.9)14 (8.8)0.95 Infection4 (6.9)6 (5.9)10 (6.3)0.81 Superficial Wound Healing12 (20.7)2 (2.0)14 (8.8)

  • CG Wood, personal communication

    Univariate analysisOdds Ratio95 % CIPOverall Complications1.981.00, 3.890.049*Peri-operative Death0.870.08, 9.790.91Readmission to Hospital0.930.33, 2.670.90Bleeding0.870.08, 9.790.91Thromboembolic1.810.50, 6.540.37Cardiac0.570.06, 5.640.63Gastrointestinal0.960.31, 3.030.95Infection1.170.32, 4.340.81Superficial Wound Healing12.912.78, 60.060.001*Chylous Ascites0.570.11, 2.900.49

  • CG Wood, personal communication*Adjusted for:Pre-operative albuminSmoking status (never, current, former)Pre-operative hemoglobinLaparoscopic vs open surgeryECOG performance statusBody mass indexAge

    Odds Ratio*95% CIp-valueSuperficial Wound Healing 19.72.13, 181.88

  • Withheld treatment for at least 2 or 3 half-lives before and after surgeryMaximum responseDays after wounding (log scale)I. inflammationII. cell proliferation and matrix depositionIII. matrix remodellingBleedingCoagulationPlatelet activationComplement activationGranulocytesPhagocytosisFibroplasiaAngiogenesisRe-epithelizationExtracelluar matrix sythesisCollagensFibronectinProteoglicansMacrophagesCytokinesStages of wound healingExtracellular matrix synthesis, degradation and remodelling Tensile strength Cellularity Vascularity

  • CG Wood, personal communication Present, initial, body of evidencewould suggest thatsignificant primary tumor downstagingwill not be realized with the current generationof targeted therapy agents

  • c.porta@smatteo.pv.it

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