PURPOSE: The present multi-center phase II study was designed to support the hypothesis that networking agents, which bind to ubiquitous accessible targets in metastatic castration-refractory prostate cancer (CRPC) may counteract neoplasia-specific aberrant cellular functions, thereby mediating PSA response (primary endpoint). METHOD: Patients with metastatic CRPC received low-dose chemotherapy with capecitabine 1 g twice daily plus dexamethasone 1 mg daily for 14 days every 3 weeks, COX-2 blockade with rofecoxib 25 mg (or etoricoxib 60 mg) daily combined with pioglitazone 60 mg daily until disease progression. RESULTS: Thirty-six consecutive patients with metastatic CRPC were enrolled, of whom n = 18 (50%) had been extensively pretreated with radio- or radionuclid therapy and n = 16 (44%) with chemotherapies; n = 8 patients (22%) were medically none-fit, having an ECOG-score of 0-2. Nine of 15 patients with PSA response >50% showed objective response. Median time to PSA response was 2.4 months (range 1.0-7.3 months). Two of 9 patients responding with PSA < 4 ng/ml showed complete resolution of skeletal lesions after 9 and 16 months; 13 patients had a stable course of disease, and 5 patients experienced progressive disease. Median progression-free survival (PFS) was 4.0 months (2.8-5.1 months) and median overall survival (OS) 14.4 months (10.7-17.2 months). Toxicities according to WHO grade II were noticed in 9 patients. CONCLUSIONS: This new combined modular therapy approach is able to induce major responses including resolution of skeletal lesions in patients with CRPC. Furthermore, the study may clinically support the above-mentioned hypothesis.
PURPOSE: The present multi-center phase II study was designed to support the hypothesis that networking agents, which bind to ubiquitous accessible targets in metastatic castration-refractory prostate cancer (CRPC) may counteract neoplasia-specific aberrant cellular functions, thereby mediating PSA response (primary endpoint). METHOD:Patients with metastatic CRPC received low-dose chemotherapy with capecitabine 1 g twice daily plus dexamethasone 1 mg daily for 14 days every 3 weeks, COX-2 blockade with rofecoxib 25 mg (or etoricoxib 60 mg) daily combined with pioglitazone 60 mg daily until disease progression. RESULTS: Thirty-six consecutive patients with metastatic CRPC were enrolled, of whom n = 18 (50%) had been extensively pretreated with radio- or radionuclid therapy and n = 16 (44%) with chemotherapies; n = 8 patients (22%) were medically none-fit, having an ECOG-score of 0-2. Nine of 15 patients with PSA response >50% showed objective response. Median time to PSA response was 2.4 months (range 1.0-7.3 months). Two of 9 patients responding with PSA < 4 ng/ml showed complete resolution of skeletal lesions after 9 and 16 months; 13 patients had a stable course of disease, and 5 patients experienced progressive disease. Median progression-free survival (PFS) was 4.0 months (2.8-5.1 months) and median overall survival (OS) 14.4 months (10.7-17.2 months). Toxicities according to WHO grade II were noticed in 9 patients. CONCLUSIONS: This new combined modular therapy approach is able to induce major responses including resolution of skeletal lesions in patients with CRPC. Furthermore, the study may clinically support the above-mentioned hypothesis.
Authors: Daniel P Petrylak; Catherine M Tangen; Maha H A Hussain; Primo N Lara; Jeffrey A Jones; Mary Ellen Taplin; Patrick A Burch; Donna Berry; Carol Moinpour; Manish Kohli; Mitchell C Benson; Eric J Small; Derek Raghavan; E David Crawford Journal: N Engl J Med Date: 2004-10-07 Impact factor: 91.245
Authors: Ian F Tannock; Ronald de Wit; William R Berry; Jozsef Horti; Anna Pluzanska; Kim N Chi; Stephane Oudard; Christine Théodore; Nicholas D James; Ingela Turesson; Mark A Rosenthal; Mario A Eisenberger Journal: N Engl J Med Date: 2004-10-07 Impact factor: 91.245
Authors: Matthew R Smith; Judith Manola; Donald S Kaufman; Daniel George; William K Oh; Elisabetta Mueller; Susan Slovin; Bruce Spiegelman; Eric Small; Philip W Kantoff Journal: Cancer Date: 2004-10-01 Impact factor: 6.860
Authors: Ramachandran Venkitaraman; Karen Thomas; Robert A Huddart; Alan Horwich; David P Dearnaley; Chris C Parker Journal: BJU Int Date: 2007-10-17 Impact factor: 5.588
Authors: Howard I Scher; Susan Halabi; Ian Tannock; Michael Morris; Cora N Sternberg; Michael A Carducci; Mario A Eisenberger; Celestia Higano; Glenn J Bubley; Robert Dreicer; Daniel Petrylak; Philip Kantoff; Ethan Basch; William Kevin Kelly; William D Figg; Eric J Small; Tomasz M Beer; George Wilding; Alison Martin; Maha Hussain Journal: J Clin Oncol Date: 2008-03-01 Impact factor: 44.544
Authors: M Vogelhuber; S Feyerabend; A Stenzl; T Suedhoff; M Schulze; J Huebner; R Oberneder; W Wieland; S Mueller; F Eichhorn; H Heinzer; K Schmidt; M Baier; A Ruebel; K Birkholz; A Bakhshandeh-Bath; R Andreesen; W Herr; A Reichle Journal: Cancer Microenviron Date: 2014-12-11
Authors: Daniel Heudobler; Michael Rechenmacher; Florian Lüke; Martin Vogelhuber; Tobias Pukrop; Wolfgang Herr; Lina Ghibelli; Christopher Gerner; Albrecht Reichle Journal: Int J Mol Sci Date: 2018-11-09 Impact factor: 5.923
Authors: Daniel Heudobler; Michael Rechenmacher; Florian Lüke; Martin Vogelhuber; Sebastian Klobuch; Simone Thomas; Tobias Pukrop; Christina Hackl; Wolfgang Herr; Lina Ghibelli; Christopher Gerner; Albrecht Reichle Journal: Front Pharmacol Date: 2018-11-28 Impact factor: 5.810
Authors: Christina Hart; Martin Vogelhuber; Daniel Wolff; Sebastian Klobuch; Lina Ghibelli; Jürgen Foell; Selim Corbacioglu; Klaus Rehe; Guy Haegeman; Simone Thomas; Wolfgang Herr; Albrecht Reichle Journal: Cancer Microenviron Date: 2015-08-11
Authors: Rachana Garg; Jorge M Blando; Carlos J Perez; Priti Lal; Michael D Feldman; Emer M Smyth; Emanuela Ricciotti; Tilo Grosser; Fernando Benavides; Marcelo G Kazanietz Journal: Oncogene Date: 2018-05-16 Impact factor: 9.867