1) Estudo mostrou que zoledronato anual preservou e aumentou a densidade óssea em homens usando agonista GnRH para câncer de próstata, reduzindo marcadores de turnover ósseo. 2) Estudo demonstrou que privação androgênica intermitente é viável para câncer de próstata localmente avançado/metastático, resultando em menos efeitos colaterais do que terapia contínua. 3) Estudo desenvolveu nomograma para prever resposta à radioterapia de salvamento após

1. PÓS ASCO 2006 Trato Genitourinário Carlos Frederico Pinto Oncologista Clínico Hospital Regional do Vale do Paraíba e Instituto de Oncologia do Vale

4. CÂNCER DE PRÓSTATA

5. Annual zoledronic acid to prevent gonadotropin-releasing hormone agonist-induced bone loss in men with prostate cancer: a randomized placebo-controlled trial. Abstract No: 4515. Authors: Michaelson MD, Lee H, Kaufman DS, Kantoff PW, Finkelstein J, Smith MR.

7. Zoledronato anual Abs# 4515 Michaelson MD, et al. ASCO 2006. Abstract 4515. Homens com câncer de próstata não metastático em uso de agonista GnRH (N = 40) Zoledronato 4 mg IV , dose única Placebo Avaliação da densidade Óssea após 12 meses

10. Phase III intermittent MAB vs continuous MAB Abstract No: 4513 Authors: Calais Da Silva FM, Calais Da Silva F, Bono A, et al.

11. Privação Androgênica Intermitente vs Contínua Calais Da Silva FM, et al. ASCO 2006. Abstract 4513. Homens com doença localmente avançada ou metastatica, PSA > 4 ng/mL (N = 626) Privação Androgenica de indução * Privação Androgenica Contínua * (n = 312) Privação Androgenica intermitente * Tratmento reiniciado quando PSA ≥ 10 ng/mL com sintomas, PSA ≥ 20 ng/mL sem sintomas ou PSA ≥ 20% do valor de nadir (n = 314) 14 sem Se PSA < 4 ng/mL ou 80% abaixo do basal *Ciproterona 200 mg/dia por 2 sem, depois injeções mensais de inibidor LH-RH + ciproterona 200 mg/dia.

15. Absolute PSA value after androgen deprivation (AD) is a strong predictor of survival in new metastatic (D2) prostate cancer (PCa): data from the Southwest Oncology Group Trial 9346 (INT-0162). Abstract No: 4517 Authors: Hussain M, Tangen CM, Schellhammer PF, et al.

16. SWOG 9346: Privação Androgênica Intermitente vs Contínua Hussain M, et al. ASCO 2006. Abstract 4517. Homens com diagnóstico de cancer de próstata metastático em início de tratamento, PSA ≥ 5 ng/mL (N = 1395) Terapia de Privação Androgênica Por 7 meses Continue terapia de privação androgênica Terapia androgênica intermitente Se PSA ≤ 4 ng/mL Mes 8

18. Public health impact of PSA doubling time after radical prostatectomy on prostate cancer specific and overall survival. Abstract No: 4568 Authors: Freedland SJ, Humphreys EB, Mangold LA, Eisenberger M, George DJ, Partin AW .

21. Predicting the outcome of salvage radiotherapy for recurrent prostate cancer after radical prostatectomy. Abstract No: 4514 Authors: Stephenson AJ, Pollack A, Kattan MW, Scardino PT, Post-Prostatectomy Radiotherapy Consortium .

26. Nomograma radioterapia de salvamento #4514

29. Phase I/II trial of the prostate-specific membrane antigen (PSMA)-targeted immunoconjugate MLN2704 in patients (pts) with progressive metastatic castration resistant prostate cancer (CRPC). Abstract no. 4500. Authors: Milowsky MI, Galsky M, George DJ, et al.

31. Preliminary results of a randomized placebo-controlled double-blind trial of weekly docetaxel combined with imatinib in men with metastatic androgen-independent prostate cancer (AIPC) and bone metastases (BM). Abstract No: 4562. Authors: Mathew P, Thall PF, Johnson MM, et al.

33. Clinical outcome of taxane-resistant (TR) hormone refractory prostate cancer (HRPC) patients (pts) treated with subsequent chemotherapy (ixabepilone (lx) or mitoxantrone/prednisone (MP). Abstract No: 4558 Authors: Lin AM, Rosenberg JE, Weinberg VK, et al.

34. Ixabepilone X mitoxantrona/pdn abs# 4558 Homens cancer de próstata resistente a hormonio e refratário a taxano (N = 82) Mitoxantrona 14mg/m2 IV 21 d (n=41) PDN 5mg 2x dia Ixabepilona 35mg/m2 IV 21d (n=41) Mitoxantrona 14mg/m2 IV 21 d (n=16) PDN 5mg 2x dia Ixabepilona 35mg/m2 IV 21d (n=29)

36. Ixabepilone X mitoxantrona/pdn abs# 4558

37. Ixabepilone X mitoxantrona/pdn abs# 4558

38. Intermittent chemotherapy in metastatic androgen-independent prostate cancer (AIPC): Initial results from ASCENT. Abstract No: 4518 Authors: T. M. Beer, C. W. Ryan, P. M. Venner, D. P. Petrylak, G. Chatta, et al.

40. Quimioterapia intermitente #4518

43. CÂNCER DE CÉLULAS RENAIS

44. Terapias atuais em CCR avançado 1 JCO 2006;24:16-24; 2 ASCO 2005; Abs 4508; 3 JCO 1999;17:2039-2043; 4 JCO 2004;22:454-463; 5 JCO 2002;20:289-296; 6 JCO 2005;23:133-141; 7 ASCO 2005; Abs 4510 40% 3%** 169* 335 Motzer et al 1,2* Escudier et al 7 Sunitinib Trial 1,2* Sorafenib TARGET (PFS 24x12m)** 11% 23% 463 255 Motzer et al 5 McDermott et al 6 Interferon-alfa Interleucina-2 Alta Dose 113 251 N Terapia Convencional 1ª Linha 3% 4% Escudier et al 3 Motzer et al 4 Citoquinas Vários (dados históricos) Terapia de 2ª Linha Convencional TKIs 2ª Linha (aprovados FDA) Taxa de Resposta (%) Referência

45. Phase III randomized trial of sunitinib malate (SU11248) versus interferon-alfa (IFN-α) as first-line systemic therapy for patients with metastatic renal cell carcinoma (mRCC) Abstract No: LBA3 Author(s): R. J. Motzer, T. E. Hutson, P. Tomczak, M. D. Michaelson, R. M. Bukowski, O. Rixe, S. Oudard, S. T. Kim, C. M. Baum, R. A. Figlin

47. Tumores Malignos do Rim, Frequência e Oncogenes Lineham WM, et al. J Urol. 2003;170:2163-2172. BHD 5% Oncocitoma BHD 5% Cromofobo FH 10% Papilar tipo 2 Met 5% Papilar tipo 1 Oncogenes Frequência Relativa Tipo VHL 75% Carcinoma Células Claras

49. Progression-Free Survival No. at Risk Sunitinib: 235 90 32 2 No. at Risk IFN-  : 152 42 18 0 (Independent Central Review) 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 Time (Months) 0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1.0 Progression Free Survival Probability Sunitinib Median: 11 months (95% CI: 10 – 12) IFN-  Median: 5 months (95% CI: 4 – 6) Hazard Ratio = 0.415 (95% CI: 0.320–0.539) P <0.000001

50. Overall Survival No. at Risk Sunitinib: 341 190 84 15 1 No. at Risk IFN-  : 296 162 66 10 0 *The observed p-value did not meet the pre-specified level of significance for this interim analysis 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 Time (Months) 0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1.0 Overall Survival Probability Sunitinib (n=375) Median not reached IFN-  (N=375) Median not reached Hazard Ratio = 0.65 (95% CI: 0.449 – 0.942) P = 0.0219*

51. Progression-Free Survival by MSKCC Risk Status* (Independent Central Review) MSKCC Risk Factors: 0 (Favorable) MSKCC risk factors: 1-2 (Intermediate) *Motzer et al. JCO 2002;20:289-296; Excludes 17 pts from IFN-  with missing data 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 Time (Months) 0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1.0 Progression Free Survival Probability Sunitinib (n=143) Median not been reached IFN-  (n=121) Median: 8 months (95% CI: 7 – NA) Hazard Ratio = 0.371 (95% CI: 0.214 – 0.643) 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 Time (Months) 0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1.0 Progression Free Survival Probability Sunitinib (n=209) Median: 11 months (95% CI: 11 – 11) IFN-  (n=212) Median: 4 months (95% CI: 3 – 4) Hazard Ratio = 0.388 (95% CI: 0.281 – 0.537)

52. Treatment-Related Adverse Events * Greater frequency, P <0.05 11/<1 * 51 7 51 Fatigue 0 13 5 * 53 Diarrhea 0 29 1 6 Chills <1 2 1 25 Stomatitis <1 16 <1 5 Myalgia 1 3 2 10 Ejection fraction decline <1 1 8 * 24 Hypertension 0 1 5 * 20 Hand-foot syndrome <1 8 0 1 Flu-like symptoms 0 34 1 7 Pyrexia Grade 3/4 Grade 3/4 IFN-  (%) 1 33 All grade 3 44 All grade Sunitinib (%) Nausea Event

54. A phase 3, randomized, 3-arm study of temsirolimus (TEMSR) or interferon-alpha (IFN) or the combination of TEMSR + IFN in the treatment of first-line, poor-risk patients with advanced renal cell carcinoma (adv RCC) A bstract No: LBA4 Author(s): G. Hudes, M. Carducci, P. Tomczak, J. Dutcher, R. Figlin, A. Kapoor, E. Staroslawska, T. O'Toole, Y. Park, L. Moore

56. Overall Survival by Treatment Arm Arm 3: IFN + Temsirolimus Arm 2: Temsirolimus Arm 1: IFN Time from Randomization, Months Probability of Survival 0.6912 0.0069 Stratified Log-Rank p Arm 3 :Arm 1 Arm 2 :Arm 1 Comparisons 210 209 207 n TEMSR + IFN Arm 3 TEMSR Arm 2 IFN Arm 1 Parameter

62. Randomized phase III trial of sorafenib in advanced renal cell carcinoma (RCC): Impact of crossover on survival. Abstract No: 4524 Author(s): T. Eisen, R. M. Bukowski, M. Staehler, C. Szczylik, S. Oudard, W. M. Stadler, B. Schwartz, R. Simantov, M. Shan, B. Escudier, For The Sorafenib TARGETs Clinical Trial Group

65. Terapias Moleculares em CCR  Tersimolimus/ RAD001/ AP23573   AG-013736  Erlotinib/ Cetuximab/ lapatinib   Sunitinib    Sorafenib  Bevacizumab mTOR Raf EGFR PDGFR VEGFR VEGFA

68. CÂNCER DE TESTÍCULO Quimioterapia de Alta Dose

69. Phase III trial of conventional-dose chemotherapy alone or with high-dose chemotherapy for metastatic germ cell tumors (GCT) patients (PTS): A cooperative group trial by Memorial Sloan-Kettering Cancer Center, ECOG, SWOG, and CALGB. Abstract No: 4510 Author(s): D. F. Bajorin, C. R. Nichols, K. A. Margolin, J. Bacik, P. G. Richardson, N. J. Vogelzang, L. Einhorn, M. Mazumdar, G. J. Bosl, R. J. Motzer

71. Single versus sequential high-dose chemotherapy (HDCT) in patients with relapsed or refractory germ-cell tumors (GCT) Abstract No: 4511 Author(s): A. Lorch, O. Rick, J. T. Hartmann, C. Kollmannsberger, B. Metzner, I. Schmidt-Wolf, W. E. Berdel, R. Schirren, J. Beyer, C. Bokemeyer, for the German Testicular Cancer Study Group

73. One course of adjuvant PEB chemotherapy versus retroperitoneal lymph node dissection in patients with stage I non-seminomatous germ-cell tumors (NSGCT): [AUO]/German testicular cancer study group [GTCSG] Trial 01-94). Abstract No: 4512 Author(s): P. Albers, R. Siener, S. Krege, H. Schmelz, K. Dieckmann, A. Heidenreich, P. Kwasny, M. Pechoel, J. Lehmann, R. Fimmers, M. Hartmann

76. Otimização de Resultados (Craig Nichols, MD – discussão ) Observação RPLND + (PEBx2) PEBx1 Quimioterapia 52x3 38x2 + 14x3 174x1 Cirurgia 5-10 174+ 1-2 #Disrupted 52 174 174 Tempo disrupted 13 sem 6-19 sem 7 sem Tempo total # 676 sem 1606 sem 1218 sem Assume reinício de atividades 1 mês após quimioterapia e 6 semanas após cirurgia

79. CÂNCER DE TESTÍCULO Follow up – Toxicidade Tardia

80. Medical Research Council trial of 2 versus 5 CT scans in the surveillance of patients with stage I non-seminomatous germ cell tumours of the testis. Abstract No: 4519 Author(s): G. M. Mead, G. J. Rustin, S. P. Stenning, P. Vasey, N. Aass, R. Huddart, M. Sokal, S. Kirk

84. A prospective study of 18FDG PET in the prediction of relapse in patients with high risk clinical stage I (CS1) non-seminomatous germ cell cancer (NSGCT): MRC study TE22. Abstract No: 4520 Author(s): R. Huddart, M. O'Doherty, A. Padhani, G. Rustin, G. Mead, J. K. Joffe, P. Vasey, S. Hain, S. J. Kirk, S. P. Stenning, L. National Cancer Research Center

86. [18F]-FDG-PET in germ cell tumors following chemotherapy: Results of the German multicenter trial. Abstract No: 4521 Author(s): M. De Wit, M. Hartmann, W. Brenner, L. Weißbach, H. Amthauer, C. Franzius, S. Kliesch, S. Krege, R. Heicappell, R. Bares, C. Bokemeyer

89. Long-term non-cancer mortality among 39,657 one-year testicular cancer survivors (TCSs). Abstract No: 4508 Author(s): S. D. Fosså, J. Chen, G. M. Dores, K. A. McGlynn, S. J. Schonfeld, L. B. Travis, Nci Testicular Cancer Research Group

95. Obrigado Carlos Frederico Pinto Oncologista Clínico Hospital Regional do Vale do Paraíba e Instituto de Oncologia do Vale [email_address]

96. OBRIGADO Sunitinib Sorafenib TEMSR ASCO 2007:

97. Associations of pain and quality of life (QOL) response with PSA response and survival of patients (pts) with metastatic hormone refractory prostate cancer (mHRPC) treated with docetaxel or mitoxantrone in the TAX-327 study. Abstract No: 4516 Authors: Berthold DR, Pond G, De Wit R, Eisenberger MA, Tannock IF.