Randomised phase II/III study of docetaxel with or without risedronate in patients with metastatic Castration Resistant Prostate Cancer (CRPC), the Netherlands Prostate Study (NePro)

• Published in: European journal of cancer (1990) Vol. 48; no. 16; pp. 2993 - 3000
• Main Authors: Meulenbeld, H.J, van Werkhoven, E.D, Coenen, J.L.L.M, Creemers, G.J, Loosveld, O.J.L, de Jong, P.C, ten Tije, A.J, Fosså, S.D, Polee, M, Gerritsen, W, Dalesio, O, de Wit, R
• Format: Journal Article
• Language: English
• Published: Kidlington Elsevier Ltd 01-11-2012; Elsevier
• Subjects: Aged; Aged, 80 and over; Androgen Antagonists - therapeutic use; Antineoplastic Agents, Phytogenic - administration & dosage; Antineoplastic Agents, Phytogenic - adverse effects; Antineoplastic Combined Chemotherapy Protocols - adverse effects; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Biological and medical sciences; Bisphosphonates; Bone Density Conservation Agents - administration & dosage; Bone metastases; Bone Neoplasms - blood; Bone Neoplasms - drug therapy; Bone Neoplasms - mortality; Bone Neoplasms - secondary; Castration; Castration Resistant Prostate Cancer; Disease Progression; Docetaxel; Etidronic Acid - administration & dosage; Etidronic Acid - analogs & derivatives; Hematology, Oncology and Palliative Medicine; Humans; Kaplan-Meier Estimate; Male; Medical sciences; Middle Aged; Netherlands; Norway; Pain - prevention & control; Pharmacology. Drug treatments; Prednisone - administration & dosage; Proportional Hazards Models; Prostate-Specific Antigen - blood; Prostatic Neoplasms - blood; Prostatic Neoplasms - drug therapy; Prostatic Neoplasms - mortality; Prostatic Neoplasms - pathology; Prostatic Neoplasms - surgery; Risedronate; Risedronate Sodium; Risk Assessment; Risk Factors; Taxoids - administration & dosage; Taxoids - adverse effects; Time Factors; Treatment Outcome; Tumors; Netherlands; Europe; Norway; Risedronate; Castration Resistant Prostate Cancer; Bisphosphonates; Bone metastases; Docetaxel; Antineoplastic agent; Phase III trial; Prostate disease; Diseases of the osteoarticular system; Antiresorptive agent; Diphosphonic acid derivatives; Randomization; Cancerology; Castration; Risedronic acid; Taxane derivatives; Phase II trial; Advanced stage; Antimitotic; Male genital diseases; Human; Urinary system disease; Malignant tumor; Resistance; Bone metastasis; Treatment; Prostate cancer; Cancer; Castration Resistant
• ISSN: 0959-8049; 1879-0852
• DOI: 10.1016/j.ejca.2012.05.014

Abstract Background This multicentre, randomised, open label, phase II/III study aimed to investigate the potential benefit of adding risedronate (R) to docetaxel (D) in patients with metastatic Castration Resistant Prostate Cancer (CRPC). Patients and methods CRPC patients with bone metastasis were randomly assigned to receive D 75 mg/m2 every 3 weeks and prednisone as first line chemotherapy, with or without R 30 mg oral once daily. The primary end-point was time to progression (TTP). A composite end-point of objective progression by RECIST criteria, PSA progression, or pain progression, whichever occurred first, was applied. The study had 80% power to detect an improvement of 30% in median TTP in the DR group (two-sided α = 0.05). Results Five hundred and ninety-two men (301 D versus 291 DR) were randomised. TTP was 7.4 [D] versus 6.5 [DR] months ( p = 0.75). PSA and pain response rates were similar, 66.3% [D] versus 65.9% [DR] and 27.9% [D] versus 31.2% [DR], respectively. Median overall survival (OS) was 18.4 [D] versus 19.2 [DR] months ( p = 0.33). There were no differences in toxicity. Conclusion The addition of the third generation bisphosphonate, risedronate, in the setting of effective first line docetaxel based chemotherapy did not increase efficacy, as indicated by the lack of improvement in TTP, OS, PSA- and pain response.