Phase II Trial of Consolidation Docetaxel and Samarium-153 in Patients With Bone Metastases From Castration-Resistant Prostate Cancer Karim Fizazi, Philippe Beuzeboc, Jean Lumbroso, Vincent Haddad, Christophe Massard, Marine Gross-Goupil, Mario Di Palma, Bernard Escudier, Christine Theodore, Yohann Loriot, Elodie Tournay, Jeannine Bouzy, and Agnes Laplanche From the Institut Gustave Roussy, University of Paris XI, Villejuif, France, Institut Curie, Paris, France. Submitted July 8, 2008; accepted Octo- ber 2, 2008; published online ahead of print at www.jco.org on April 13, 2009. Authors’ disclosures of potential con- flicts of interest and author contribu- tions are found at the end of this article. Corresponding author: Karim Fizazi, MD, PhD, Department of Medicine, Institut Gustave Roussy, 39 rue Camille Desmoulins, 94800 Villejuif, France; e-mail: fizazi@igr.fr. © 2009 by American Society of Clinical Oncology 0732-183X/09/2715-2429/$20.00 DOI: 10.1200/JCO.2008.18.9811 A B S T R A C T Purpose To assess docetaxel combined with samarium-153– ethylene diamine tetramethylene phosphonic acid (EDTMP), a radiopharmaceutical with a high affinity for bone, in patients with castration- resistant prostate cancer (CRPC). Patients and Methods Patients with bone metastases from CRPC who achieved a response or stabilization after four cycles of docetaxel and estramustine were given consolidation docetaxel 20 mg/m 2 /wk for 6 weeks and samarium-153-EDTMP (37 MBq/kg) during week 1. Prostate-specific antigen (PSA) response was assessed by using consensus criteria, and pain was assessed by using a visual analog scale (VAS). This study used a Simon two-step design with PSA–progression-free survival (PFS) as the primary end point. Results Forty-three patients were included in the trial. A PSA response was obtained in 77% (95% CI, 61% to 82%). The pain response rate was 69% (95% CI, 49% to 85%). At least five of the six planned weekly injections of docetaxel were administered to 34 patients (81%). The consolidation docetaxel–samarium-153–EDTMP regimen was well tolerated; there was no febrile neutropenia, and only two episodes (5%) of rapidly reversible grade 3 thrombocytopenia occurred. Although a serum PSA relapse eventually occurred in all patient cases, this regimen resulted in pain control in the long-term. The median PSA-PFS was 6.4 months (95% CI, 6 to 7 months). The median survival was 29 months (95% CI, 22 to 31); the 1-year survival rate was 77% (62% to 87%); and the 2-year survival rate was 56% (41% to 70%). Conclusion Combining docetaxel and samarium-153–EDTMP in patients with bone metastases from CRPC is well tolerated, and it yields major pain relief that persists long after treatment. Overall survival compares favorably with that expected in this population of patients, most of whom exhibit symptoms. J Clin Oncol 27:2429-2435. © 2009 by American Society of Clinical Oncology INTRODUCTION Prostate cancer is the most common cancer and the second leading cause of cancer in men in most West- ern countries. 1 The bone is the site of metastatic spread in more than 80% of patient cases. Bone metastases are associated with high morbidity, in- cluding mainly pain, pathologic fractures, spinal compression, bone marrow insufficiency, and fa- tigue, and they are eventually associated with death. Although advanced prostate cancer is initially sensitive to androgen deprivation therapy, most deaths occur after progression to the castration- resistant status. In this setting, chemotherapy has improved the quality of life 2 PFS, 3 and, more re- cently, overall survival with the use of docetaxel- based regimens. 4,5 However, the overall survival benefit is limited, as median survival has lasted 19 months in recent large phase III randomized trials and only 14 months in symptomatic patients. 6 Estramustine phosphate has demonstrated both hormonal and nonhormonal effects in vivo. 7 It in- hibits microtubule function by binding to both tu- bulin 8,9 and microtubule-associated proteins, 10 and it was reported to increase docetaxel-induced re- sponse rates in castration-resistant prostate cancer (CRPC). However, in the absence of a sufficiently powered randomized trial, debates continue about JOURNAL OF CLINICAL ONCOLOGY O R I G I N A L R E P O R T VOLUME 27  NUMBER 15  MAY 20 2009 © 2009 by American Society of Clinical Oncology 2429 Downloaded from ascopubs.org by 3.236.106.28 on June 25, 2022 from 003.236.106.028 Copyright © 2022 American Society of Clinical Oncology. All rights reserved.