Current Clinical Trials in Castrate-Resistant Prostate Cancer
Tóm tắt
Seven years passed since docetaxel/prednisone demonstrated and overall survival benefit, leading to its approval by the FDA for metastatic castration resistant prostate cancer. In 2010, two new treatments, sipuleucel-T and cabazitaxel, were approved by the United States Food and Drug Administration for men with castration-resistant prostate cancer, based upon improvement in overall survival. The progress that has been made in understanding the biological basis of disease progression, particularly the role of the continued activation of the androgen receptor, have led to new treatments that will further improve survival in these patients. Abiraterone, a drug that depletes both intracellular and extracellular sources of testosterone, demonstrated a 3.9-month improvement in survival in patients who failed docetaxel-based chemotherapy. Other drugs targeting the androgen-receptor axis, such as TAK-700 and MDV3100, have demonstrated significant activity in phase 1 and 2 studies, and are currently in phase 3. Agents that target angiogenesis, bone, and novel apoptotic proteins currently are under investigation, either as single agents or in combination with chemotherapy. The challenge for the development of clinical trials will be how these compounds will be sequenced in the future.
Tài liệu tham khảo
Tannock IF, de Wit R, Berry WR, Horti J, Pluzanska A, Chi KN, et al. Docetaxel plus prednisone or mitoxantrone plus prednisone for advanced prostate cancer. N Engl J Med. 2004;351(15):1502–12.
Petrylak DP, Tangen CM, Hussain MH, Lara Jr PN, Jones JA, Taplin ME, et al. Docetaxel and estramustine compared with mitoxantrone and prednisone for advanced refractory prostate cancer. N Engl J Med. 2004;351(15):1513–20.
• de Bono JS, Oudard S, Ozguroglu M, Hansen S, Machiels JP, Kocak I, et al. Prednisone plus cabazitaxel or mitoxantrone for metastatic castration-resistant prostate cancer progressing after docetaxel treatment: a randomised open-label trial. Lancet Oct 2;376(9747):1147–54. In this article, a survival benefit was demonstrated in those patients who received cabazitaxel.
•• Kantoff PW, Higano CS, Shore ND, Berger ER, Small EJ, Penson DF, et al. Sipuleucel-T immunotherapy for castration-resistant prostate cancer. N Engl J Med. 2010;363(5):411–22. This was the first study to demonstrate a survival benefit in men treated with immune therapy for castration-resistant prostate cancer.
Higano CS, Schellhammer PF, Small EJ, Burch PA, Nemunaitis J, Yuh L, et al. Integrated data from 2 randomized, double-blind, placebo-controlled, phase 3 trials of active cellular immunotherapy with sipuleucel-T in advanced prostate cancer. Cancer. 2009;115(16):3670–9.
Small EJ, Schellhammer PF, Higano CS, Redfern CH, Nemunaitis JJ, Valone FH, et al. Placebo-controlled phase III trial of immunologic therapy with sipuleucel-T (APC8015) in patients with metastatic, asymptomatic hormone refractory prostate cancer. J Clin Oncol. 2006;24(19):3089–94.
Higano C, Saad F, Somer B, Curti B, Petrylak D, Drake CG, et al. A phase III trial of GVAX immunotherapy for prostate cancer versus docetaxel plus prednisone in asymptomatic, castration-resistant prostate cancer (CRPC). 2009 Genitourinary Cancers Symposium2009;LBA150.
Kantoff PW, Schuetz TJ, Blumenstein BA, Glode LM, Bilhartz DL, Wyand M, et al. Overall survival analysis of a phase II randomized controlled trial of a Poxviral-based PSA-targeted immunotherapy in metastatic castration-resistant prostate cancer. J Clin Oncol. 28(7):1099–105.
Madan RA, Gulley JL, Fojo T, Dahut WL. Therapeutic cancer vaccines in prostate cancer: the paradox of improved survival without changes in time to progression. Oncologist. 15(9):969–75.
Slovin SF, Beer TM, Higano CS, Tejwani, Hamid O, Picus J, et al. Initial phase II experience of ipilimumab (IPI) alone and in combination with radiotherapy (XRT) in patients with metastatic castration-resistant prostate cancer (mCRPC). J Clin Oncol. 2009;27:15s, 2009 (suppl; abstr 5138).
Mohler JL. Castration-recurrent prostate cancer is not androgen-independent. Adv Exp Med Biol. 2008;617:223–34.
Mohler JL, Gregory CW, Ford 3rd OH, Kim D, Weaver CM, Petrusz P, et al. The androgen axis in recurrent prostate cancer. Clin Cancer Res. 2004;10(2):440–8.
Ryan CJ, Smith MR, Fong L, Rosenberg JE, Kantoff P, Raynaud F, et al. Phase I clinical trial of the CYP17 inhibitor abiraterone acetate demonstrating clinical activity in patients with castration-resistant prostate cancer who received prior ketoconazole therapy. J Clin Oncol. 28(9):1481–8.
Attard G, Reid AH, A’Hern R, Parker C, Oommen NB, Folkerd E, et al. Selective inhibition of CYP17 with abiraterone acetate is highly active in the treatment of castration-resistant prostate cancer. J Clin Oncol. 2009;27(23):3742–8.
Vasaitis TS, Bruno RD, Njar VC. CYP17 inhibitors for prostate cancer therapy. J Steroid Biochem Mol Biol. Nov 17.
Tran C, Ouk S, Clegg NJ, Chen Y, Watson PA, Arora V, et al. Development of a second-generation antiandrogen for treatment of advanced prostate cancer. Science. 2009;324(5928):787–90.
Kelly WK, Scher HI. Prostate specific antigen decline after antiandrogen withdrawal: the flutamide withdrawal syndrome. J Urol. 1993;149(3):607–9.
Mita AC, Denis LJ, Rowinsky EK, Debono JS, Goetz AD, Ochoa L, et al. Phase I and pharmacokinetic study of XRP6258 (RPR 116258A), a novel taxane, administered as a 1-hour infusion every 3 weeks in patients with advanced solid tumors. Clin Cancer Res. 2009;15(2):723–30.
Clinicaltrials.gov. XRP6258 Plus Prednisone Compared to Mitoxantrone Plus Prednisone in Hormone Refractory Metastatic Prostate Cancer (TROPIC). Available at http://clinicaltrials.gov/ct2/show/NCT00417079. Accessed March 2011.
Carducci MA, Nelson JB, Bowling MK, Rogers T, Eisenberger MA, Sinibaldi V, et al. Atrasentan, an endothelin-receptor antagonist for refractory adenocarcinomas: safety and pharmacokinetics. J Clin Oncol. 2002;20(8):2171–80.
Carducci MA, Padley RJ, Breul J, Vogelzang NJ, Zonnenberg BA, Daliani DD, et al. Effect of endothelin-A receptor blockade with atrasentan on tumor progression in men with hormone-refractory prostate cancer: a randomized, phase II, placebo-controlled trial. J Clin Oncol. 2003;21(4):679–89.
Carducci MA, Saad F, Abrahamsson PA, Dearnaley DP, Schulman CC, North SA, et al. A phase 3 randomized controlled trial of the efficacy and safety of atrasentan in men with metastatic hormone-refractory prostate cancer. Cancer. 2007;110(9):1959–66.
Armstrong AJ, Creel P, Turnbull J, Moore C, Jaffe TA, Haley S, et al. A phase I–II study of docetaxel and atrasentan in men with castration-resistant metastatic prostate cancer. Clin Cancer Res. 2008;14(19):6270–6.
Petrylak DP, Mohile SG, Shelton G, Carr RA, Steinberg J, Sleep D, et al. Pharmacokinetics (PK), safety and tolerability of atrasentan (ABT-627, ATN) in combination with docetaxel (DOC) in men with hormone refractory prostate cancer (HRPC). J Clin Oncol. 2006;2006 ASCO Annual Meeting Proceedings Part I. Vol 24, No. 18S (June 20 Supplement), 2006: 14512.
James ND, Caty A, Payne H, Borre M, Zonnenberg BA, Beuzeboc P, et al. Final safety and efficacy analysis of the specific endothelin A receptor antagonist zibotentan (ZD4054) in patients with metastatic castration-resistant prostate cancer and bone metastases who were pain-free or mildly symptomatic for pain: a double-blind, placebo-controlled, randomized Phase II trial. BJU Int. 106(7):966–73.
Nelson JB, Fizazi K, Miller K, Higano CS, Moul JW, Morris T, et al. Phase III study of the efficacy and safety of zibotentan (ZD4054) in patients with bone metastatic castration-resistant prostate cancer (CRPC). J Clin Oncol. 2011;29:(suppl 7; abstr 117) 2011;29:2011 (suppl 7; abstr 117).
Araujo JC, Poblenz A, Corn P, Parikh NU, Starbuck MW, Thompson JT, et al. Dasatinib inhibits both osteoclast activation and prostate cancer PC-3-cell-induced osteoclast formation. Cancer Biol Ther. 2009;8(22):2153–9.
Yu EY, Wilding G, Posadas E, Gross M, Culine S, Massard C, et al. Phase II study of dasatinib in patients with metastatic castration-resistant prostate cancer. Clin Cancer Res. 2009;15(23):7421–8.
Fizazi K, Carducci MA, Smith MR, Damião R, Brown L, Karsh P, et al. A randomized phase III trial of denosumab versus zoledronic acid in patients with bone metastases from castration-resistant prostate cancer. J Clin Oncol. 2010;28:18s, (suppl; abstr LBA4507) 2010.
Nilsson S, Franzen L, Parker C, Tyrrell C, Blom R, Tennvall J, et al. Bone-targeted radium-223 in symptomatic, hormone-refractory prostate cancer: a randomised, multicentre, placebo-controlled phase II study. Lancet Oncol. 2007;8(7):587–94.
Steinberg J, Oyasu R, Lang S, Sintich S, Rademaker A, Lee C, et al. Intracellular levels of SGP-2 (Clusterin) correlate with tumor grade in prostate cancer. Clin Cancer Res. 1997;3(10):1707–11.
Chi KN, Hotte SJ, Yu EY, Tu D, Eigl BJ, Tannock I, et al. Randomized phase II study of docetaxel and prednisone with or without OGX-011 in patients with metastatic castration-resistant prostate cancer. J Clin Oncol. 28(27):4247–54.
Folkman J. Angiogenesis in cancer, vascular, rheumatoid and other disease. Nat Med. 1995;1(1):27–31.
George DJ, Halabi S, Shepard TF, Vogelzang NJ, Hayes DF, Small EJ, et al. Prognostic significance of plasma vascular endothelial growth factor levels in patients with hormone-refractory prostate cancer treated on Cancer and Leukemia Group B 9480. Clin Cancer Res. 2001;7(7):1932–6.
Kelly WK, Halabi S, Carducci MA, George DJ, Mahoney JF, Stadler WM, et al. A randomized, double-blind, placebo-controlled phase III trial comparing docetaxel, prednisone, and placebo with docetaxel, prednisone, and bevacizumab in men with metastatic castration-resistant prostate cancer (mCRPC): Survival results of CALGB 90401. J Clin Oncol. 2010;28(18S):(suppl; abstr LBA4511).
Tew WP, Gordon M, Murren J, Dupont J, Pezzulli S, Aghajanian C, et al. Phase 1 study of aflibercept administered subcutaneously to patients with advanced solid tumors. Clin Cancer Res. 16(1):358–66.
Lestingi TM, Tolzien K, Kelby SK, Nabhan C. Safety and activity of lenalidomide (LEN) in elderly patients (pts) with chemotherapy-naive, castration-resistant prostate cancer (CRPC). J Clin Oncol. 2010;28(suppl; abstr e15125).
Figg WD, Dahut W, Duray P, Hamilton M, Tompkins A, Steinberg SM, et al. A randomized phase II trial of thalidomide, an angiogenesis inhibitor, in patients with androgen-independent prostate cancer. Clin Cancer Res. 2001;7(7):1888–93.
Petrylak DP, Resto-Garces K, Tibyan M, Mohile SG. A phase I open-label study using lenalidomide and docetaxel in castration- resistant prostate cancer. J Clin Oncol. 2009;27:15s, (suppl; abstr 5156) 2009.
Clinicaltrials.gov. Study to Evaluate Safety and Effectiveness of Lenalidomide in Combination With Docetaxel and Prednisone for Patients With Castrate-Resistant Prostate Cancer (Mainsail). Available at http://clinicaltrials.gov/ct2/show/NCT00988208. Accessed March 2011.
Knudsen BS, Gmyrek GA, Inra J, Scherr DS, Vaughan ED, Nanus DM, et al. High expression of the Met receptor in prostate cancer metastasis to bone. Urology. 2002;60(6):1113–7.
Smith DC, Spira A, De Grève J, LH, SH, Lin C, et al. Phase 2 Study of XL184 in a Cohort of Patients with Castration Resistant Prostate Cancer (CRPC) and Measurable Soft Tissue Disease. Proceedings ESMO, 20102010.