Multimodal treatment for high-risk prostate cancer with high-dose intensity-modulated radiation therapy preceded or not by radical prostatectomy, concurrent intensified-dose docetaxel and long-term androgen deprivation therapy: results of a prospective phase II trial

Radiation Oncology

Filiberto Zattoni⁶  Antonio Garbeglio⁵  Francesca Valent²  Vito Palumbo⁶  Michele Gnech⁶  Fabio Zattoni⁶  Pirus Ghadjar⁴  Gianluca Giannarini¹  Roberto Bortolus³  Andrea Guttilla⁶ 

[1] Department of Urology, University of Bern, Inselspital, Bern, Switzerland;Epidemiological Service, Direzione Centrale Salute, Integrazione Sociosanitaria e Politiche Sociali, Regione Autonoma Friuli Venezia Giulia, Udine, Italy;Department of Radiation Oncology, National Cancer Institute Aviano, Aviano, PN, Italy;Department of Radiation Oncology, University of Bern, Inselspital, Bern, Switzerland;Department of General Surgery, Division of Urology, Azienda Ospedaliera “Santa Maria degli Angeli”, Pordenone, Italy;Department of Oncological, Surgical and Gastroenterological Sciences, Urology Clinic, University of Padua, Padua 35128, Italy

关键词: Phase II;    Clinical trial;    Toxicity;    Docetaxel;    Chemotherapy;    Androgen deprivation therapy;    Prostatectomy;    Intensity-modulated;    Radiotherapy;    Prostatic neoplasms;   

Others  :  815018
DOI  :  10.1186/1748-717X-9-24

 received in 2013-09-25, accepted in 2013-12-30,  发布年份 2014

【 摘 要 】

Background

The optimal management of high-risk prostate cancer remains uncertain. In this study we assessed the safety and efficacy of a novel multimodal treatment paradigm for high-risk prostate cancer.

Methods

This was a prospective phase II trial including 35 patients with newly diagnosed high-risk localized or locally advanced prostate cancer treated with high-dose intensity-modulated radiation therapy preceded or not by radical prostatectomy, concurrent intensified-dose docetaxel-based chemotherapy and long-term androgen deprivation therapy. Primary endpoint was acute and late toxicity evaluated with the Common Terminology Criteria for Adverse Events version 3.0. Secondary endpoint was biochemical and clinical recurrence-free survival explored with the Kaplan-Meier method.

Results

Acute gastro-intestinal and genito-urinary toxicity was grade 2 in 23% and 20% of patients, and grade 3 in 9% and 3% of patients, respectively. Acute blood/bone marrow toxicity was grade 2 in 20% of patients. No acute grade ≥4 toxicity was observed. Late gastro-intestinal and genito-urinary toxicity was grade 2 in 9% of patients each. No late grade ≥3 toxicity was observed. Median follow-up was 63 months (interquartile range 31–79). Actuarial 5-year biochemical and clinical recurrence-free survival rate was 55% (95% confidence interval, 35-75%) and 70% (95% confidence interval, 52-88%), respectively.

Conclusions

In our phase II trial testing a novel multimodal treatment paradigm for high-risk prostate cancer, toxicity was acceptably low and mid-term oncological outcome was good. This treatment paradigm, thus, may warrant further evaluation in phase III randomized trials.

【 授权许可】

   
2014 Guttilla et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

【 参考文献 】

• [1]Yossepowitch O, Eggener SE, Serio AM, Carver BS, Bianco FJ Jr, Scardino PT, Eastham JA: Secondary therapy, metastatic progression, and cancer-specific mortality in men with clinically high-risk prostate cancer treated with radical prostatectomy. Eur Urol 2008, 53:950-959.
• [2]Cooperberg MR, Broering JM, Carroll PR: Time trends and local variation in primary treatment of localized prostate cancer. J Clin Oncol 2010, 28:1117-1123.
• [3]Horwitz EM, Bae K, Hanks GE, Porter A, Grignon DJ, Brereton HD, Venkatesan V, Lawton CA, Rosenthal SA, Sandler HM, Shipley WU: Ten-year follow-up of radiation therapy oncology group protocol 92–02: a phase III trial of the duration of elective androgen deprivation in locally advanced prostate cancer. J Clin Oncol 2008, 26:2497-2504.
• [4]Walz J, Joniau S, Chun FK, Isbarn H, Jeldres C, Yossepowitch O, Chao-Yu H, Klein EA, Scardino PT, Reuther A, Poppel HV, Graefen M, Huland H, Karakiewicz PI: Pathological results and rates of treatment failure in high-risk prostate cancer patients after radical prostatectomy. BJU Int 2011, 107:765-770.
• [5]European Association of Urology Guidelines on Prostate Cancer. Available at http://www.uroweb.org webcite, accessed on December 20, 2013
• [6]National Comprehensive Cancer Network Clinical Practice Guidelines in Oncology, Prostate Cancer, Version 1.2014. Available at http://www.nccn.org webcite, accessed on December 20, 2013
• [7]Bria E, Cuppone F, Giannarelli D, Milella M, Ruggeri EM, Sperduti I, Pinnarò P, Terzoli E, Cognetti F, Carlini P: Does hormone treatment added to radiotherapy improve outcome in locally advanced prostate cancer?: meta-analysis of randomized trials. Cancer 2009, 115:3446-3456.
• [8]Bastian PJ, Boorjian SA, Bossi A, Briganti A, Heidenreich A, Freedland SJ, Montorsi F, Roach M 3rd, Schröder F, van Poppel H, Stief CG, Stephenson AJ, Zelefsky MJ: High-risk prostate cancer: from definition to contemporary management. Eur Urol 2012, 61:1096-1106.
• [9]Tannock IF, de Wit R, Berry WR, Horti J, Pluzanska A, Chi KN, Oudard S, Théodore C, James ND, Turesson I, Rosenthal MA, Eisenberger MA, TAX 327 Investigators: Docetaxel plus prednisone or mitoxantrone plus prednisone for advanced prostate cancer. N Engl J Med 2004, 351:1502-1512.
• [10]Petrylak DP, Tangen CM, Hussain MH, Lara PN Jr, Jones JA, Taplin ME, Burch PA, Berry D, Moinpour C, Kohli M, Benson MC, Small EJ, Raghavan D, Crawford ED: Docetaxel and estramustine compared with mitoxantrone and prednisone for advanced refractory prostate cancer. N Engl J Med 2004, 351:1513-1520.
• [11]Varveris H, Mazonakis M, Vlachaki M, Kachris S, Lyraraki E, Zoras O, Maris T, Froudarakis M, Velegrakis J, Perysinakis C, Damilakis J, Samonis G: A phase I trial of weekly docetaxel and cisplatinum combined to concurrent hyperfractionated radiotherapy for non-small cell lung cancer and squamous cell carcinoma of head and neck. Oncol Rep 2003, 10:185-195.
• [12]Alvarez EA, Wolfson AH, Pearson JM, Crisp MP, Mendez LE, Lambrou NC, Lucci JA 3rd: A phase I study of docetaxel as a radio-sensitizer for locally advanced squamous cell cervical cancer. Gynecol Oncol 2009, 113:195-199.
• [13]Shiota M, Kashiwagi E, Yokomizo A, Takeuchi A, Dejima T, Song Y, Tatsugami K, Inokuchi J, Uchiumi T, Naito S: Interaction between docetaxel resistance and castration resistance in prostate cancer: implications of Twist1, YB-1, and androgen receptor. Prostate 2013, 73:1336-1344.
• [14]Kumar P, Perrotti M, Weiss R, Todd M, Goodin S, Cummings K, DiPaola RS: Phase I trial of weekly docetaxel with concurrent three-dimensional conformal radiation therapy in the treatment of unfavorable localized adenocarcinoma of the prostate. J Clin Oncol 2004, 22:1909-1915.
• [15]Perrotti M, Doyle T, Kumar P, McLeod D, Badger W, Prater S, Moran M, Rosenberg S, Bonatsos C, Kreitner C, Kiehl R, Chang T, Kolodziej M: Phase I/II trial of docetaxel and concurrent radiation therapy in localized high risk prostate cancer (AGUSG 03–10). Urol Oncol 2008, 26:276-280.
• [16]Bolla M, Hannoun-Levi JM, Ferrero JM, Maingon P, Buffet-Miny J, Bougnoux A, Bauer J, Descotes JL, Fourneret P, Jover F, Colonna M: Concurrent and adjuvant docetaxel with three-dimensional conformal radiation therapy plus androgen deprivation for high-risk prostate cancer: preliminary results of a multicentre phase II trial. Radiother Oncol 2010, 97:312-317.
• [17]Bader P, Burkhard FC, Markwalder R, Studer UE: Disease progression and survival of patients with positive lymph nodes after radical prostatectomy. Is there a chance of cure? J Urol 2003, 169:849-854.
• [18]Dindo D, Demartines N, Clavien PA: Classification of surgical complications: a new proposal with evaluation in a cohort of 6,336 patients and results of a survey. Ann Surg 2004, 240:205-213.
• [19]Trotti A, Colevas AD, Setser A, Rusch V, Jaques D, Budach V, Langer C, Murphy B, Cumberlin R, Coleman CN, Rubin P: CTCAE v3.0: development of a comprehensive grading system for the adverse effects of cancer treatment. Semin Radiat Oncol 2003, 13:176-181.
• [20]Matzinger O, Duclos F, van den Bergh A, Carrie C, Villà S, Kitsios P, Poortmans P, Sundar S, van der Steen-Banasik EM, Gulyban A, Collette L, Bolla M, EORTC Radiation Oncology Group: Acute toxicity of curative radiotherapy for intermediate- and high-risk localised prostate cancer in the EORTC trial 22991. Eur J Cancer 2009, 45:2825-2834.
• [21]Roach M 3rd, Hanks G, Thames H Jr, Schellhammer P, Shipley WU, Sokol GH, Sandler H: Defining biochemical failure following radiotherapy with or without hormonal therapy in men with clinically localized prostate cancer: recommendations of the RTOG-ASTRO Phoenix Consensus Conference. Int J Radiat Oncol Biol Phys 2006, 65:965-974.
• [22]Simon R: Optimal two-stage designs for phase II clinical trials. Control Clin Trials 1989, 10:1-10.
• [23]Sanfilippo NJ, Taneja SS, Chachoua A, Lepor H, Formenti SC: Phase I/II study of biweekly paclitaxel and radiation in androgen-ablated locally advanced prostate cancer. J Clin Oncol 2008, 26:2973-2978.
• [24]Hussain A, Wu Y, Mirmiran A, DiBiase S, Goloubeva O, Bridges B, Mannuel H, Engstrom C, Dawson N, Amin P, Kwok Y: Long-term follow-up of a prospective trial of trimodality therapy of weekly paclitaxel, radiation, and androgen deprivation in high-risk prostate cancer with or without prior prostatectomy. Int J Radiat Oncol Biol Phys 2012, 82:167-174.
• [25]Chen RC, Rosenman JG, Hoffman LG, Chiu WK, Wang AZ, Pruthi RS, Wallen EM, Crane JM, Kim WY, Rathmell WK, Godley PA, Whang YE: Phase I study of concurrent weekly docetaxel, high-dose intensity-modulated radiation therapy (IMRT) and androgen-deprivation therapy (ADT) for high-risk prostate cancer. BJU Int 2012, 110:E721-E726.
• [26]Viani GA, Stefano EJ, Afonso SL: Higher-than-conventional radiation doses in localized prostate cancer treatment: a meta-analysis of randomized, controlled trials. Int J Radiat Oncol Biol Phys 2009, 74:1405-1418.
• [27]Cahlon O, Hunt M, Zelefsky MJ: Intensity-modulated radiation therapy: supportive data for prostate cancer. Semin Radiat Oncol 2008, 18:48-57.
• [28]Bolla M, van Poppel H, Tombal B, Vekemans K, Da Pozzo L, de Reijke TM, Verbaeys A, Bosset JF, van Velthoven R, Colombel M, van de Beek C, Verhagen P, van den Bergh A, Sternberg C, Gasser T, van Tienhoven G, Scalliet P, Haustermans K, Collette L, European organisation for Research and Treatment of Cancer, Radiation Oncology and Genito-Urinary Groups: Postoperative radiotherapy after radical prostatectomy for high-risk prostate cancer: long-term results of a randomised controlled trial (EORTC trial 22911). Lancet 2012, 380:2018-2027.
• [29]Spratt DE, Pei X, Yamada J, Kollmeier MA, Cox B, Zelefsky MJ: Long-term survival and toxicity in patients treated with high-dose intensity modulated radiation therapy for localized prostate cancer. Int J Radiat Oncol Biol Phys 2013, 85:686-692.
• [30]Wiegel T, Bottke D, Steiner U, Siegmann A, Golz R, Störkel S, Willich N, Semjonow A, Souchon R, Stöckle M, Rübe C, Weissbach L, Althaus P, Rebmann U, Kälble T, Feldmann HJ, Wirth M, Hinke A, Hinkelbein W, Miller K: Phase III postoperative adjuvant radiotherapy after radical prostatectomy compared with radical prostatectomy alone in pT3 prostate cancer with postoperative undetectable prostate-specific antigen: ARO 96-02/AUO AP 09/95. J Clin Oncol 2009, 27:2924-2930.