Literature DB >> 20512580

A clinical phase I/II trial with the monoclonal antibody cG250 (RENCAREX®) and interferon-alpha-2a in metastatic renal cell carcinoma patients.

M Siebels1, K Rohrmann, R Oberneder, M Stahler, N Haseke, J Beck, R Hofmann, M Kindler, P Kloepfer, C Stief.   

Abstract

PURPOSE: To evaluate the efficacy and safety of WX-G250, a chimeric monoclonal antibody that binds to carboxy anhydrase IX, combined with low-dose interferon-alpha (LD-IFNα) in patients with progressive metastatic renal cell carcinoma (mRCC). PATIENTS AND METHODS: Thirty-one patients, nephrectomized for the primary tumor, clear cell progressive mRCC, were enrolled to receive weekly infusions of WX-G250 (20 mg i.v.; week 2-12) combined with LD-IFNα (3 MIU s.c. 3 times/week; week 1-12). At week 16, patients were evaluated for response and stratified into two groups: (a) responders into the extended treatment group for an additional 6 weeks of treatment or (b) the progressive group with no further study treatment.
RESULTS: Of the 31 treated patients, 26 were evaluable for response to treatment. Two patients showed partial remission and 14 patients had stable disease as assessed in week 16. One patient experienced partial remission resulting in a complete remission lasting at least 17 months. Nine patients had durable stable disease of 24 weeks or longer. Clinical benefit was obtained in 42% (11/26) patients. The median overall survival achieved was 30 months and the 2-year survival was 57%. Patients receiving extended treatment showed a significantly longer 2-year survival rate than discontinued patients (79 vs. 30%; P=0.0083). In general, treatment was well tolerated with little toxicity.
CONCLUSION: Treatment with the antibody WX-G250 in combination with LD-IFNα is safe, well tolerated, led to clinically meaningful disease stabilization and demonstrated clinical benefit in this progressive mRCC patient population.

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Year:  2010        PMID: 20512580     DOI: 10.1007/s00345-010-0570-2

Source DB:  PubMed          Journal:  World J Urol        ISSN: 0724-4983            Impact factor:   4.226


  20 in total

1.  Molecular cloning and immunogenicity of renal cell carcinoma-associated antigen G250.

Authors:  K Grabmaier; J L Vissers; M C De Weijert; J C Oosterwijk-Wakka; A Van Bokhoven; R H Brakenhoff; E Noessner; P A Mulders; G Merkx; C G Figdor; G J Adema; E Oosterwijk
Journal:  Int J Cancer       Date:  2000-03-15       Impact factor: 7.396

2.  Multicenter phase II trial of interleukin-2, interferon-alpha, and 13-cis-retinoic acid in patients with metastatic renal-cell carcinoma.

Authors:  W M Stadler; T Kuzel; M Dumas; N J Vogelzang
Journal:  J Clin Oncol       Date:  1998-05       Impact factor: 44.544

3.  Monoclonal antibody G 250 recognizes a determinant present in renal-cell carcinoma and absent from normal kidney.

Authors:  E Oosterwijk; D J Ruiter; P J Hoedemaeker; E K Pauwels; U Jonas; J Zwartendijk; S O Warnaar
Journal:  Int J Cancer       Date:  1986-10-15       Impact factor: 7.396

4.  Sorafenib in advanced clear-cell renal-cell carcinoma.

Authors:  Bernard Escudier; Tim Eisen; Walter M Stadler; Cezary Szczylik; Stéphane Oudard; Michael Siebels; Sylvie Negrier; Christine Chevreau; Ewa Solska; Apurva A Desai; Frédéric Rolland; Tomasz Demkow; Thomas E Hutson; Martin Gore; Scott Freeman; Brian Schwartz; Minghua Shan; Ronit Simantov; Ronald M Bukowski
Journal:  N Engl J Med       Date:  2007-01-11       Impact factor: 91.245

5.  Sunitinib versus interferon alfa in metastatic renal-cell carcinoma.

Authors:  Robert J Motzer; Thomas E Hutson; Piotr Tomczak; M Dror Michaelson; Ronald M Bukowski; Olivier Rixe; Stéphane Oudard; Sylvie Negrier; Cezary Szczylik; Sindy T Kim; Isan Chen; Paul W Bycott; Charles M Baum; Robert A Figlin
Journal:  N Engl J Med       Date:  2007-01-11       Impact factor: 91.245

6.  Subcutaneous interleukin-2 and interferon alpha in the treatment of patients with metastatic renal cell carcinoma-Less efficacy compared with intravenous interleukin-2 and interferon alpha. Results of a multicenter Phase II trial from the Groupe Français d'Immunothérapie.

Authors:  Alain Ravaud; Rémy Delva; Fréderic Gomez; Christine Chevreau; Jean-Yves Douillard; Jean Peny; Bruno Coudert; Sylvie Négrier
Journal:  Cancer       Date:  2002-12-01       Impact factor: 6.860

7.  A clinical trial with chimeric monoclonal antibody WX-G250 and low dose interleukin-2 pulsing scheme for advanced renal cell carcinoma.

Authors:  I Bleumer; E Oosterwijk; J C Oosterwijk-Wakka; M C W Völler; S Melchior; S O Warnaar; C Mala; J Beck; P F A Mulders
Journal:  J Urol       Date:  2006-01       Impact factor: 7.450

8.  Temsirolimus, interferon alfa, or both for advanced renal-cell carcinoma.

Authors:  Gary Hudes; Michael Carducci; Piotr Tomczak; Janice Dutcher; Robert Figlin; Anil Kapoor; Elzbieta Staroslawska; Jeffrey Sosman; David McDermott; István Bodrogi; Zoran Kovacevic; Vladimir Lesovoy; Ingo G H Schmidt-Wolf; Olga Barbarash; Erhan Gokmen; Timothy O'Toole; Stephanie Lustgarten; Laurence Moore; Robert J Motzer
Journal:  N Engl J Med       Date:  2007-05-31       Impact factor: 91.245

9.  Interleukin-2- and interferon alfa-2a-based immunochemotherapy in advanced renal cell carcinoma: a Prospectively Randomized Trial of the German Cooperative Renal Carcinoma Chemoimmunotherapy Group (DGCIN).

Authors:  J Atzpodien; H Kirchner; U Jonas; L Bergmann; H Schott; H Heynemann; P Fornara; S A Loening; J Roigas; S C Müller; H Bodenstein; S Pomer; B Metzner; U Rebmann; R Oberneder; M Siebels; T Wandert; T Puchberger; M Reitz
Journal:  J Clin Oncol       Date:  2004-02-23       Impact factor: 44.544

10.  IL-2 in combination with IFN- alpha and 5-FU versus tamoxifen in metastatic renal cell carcinoma: long-term results of a controlled randomized clinical trial.

Authors:  J Atzpodien; H Kirchner; H J Illiger; B Metzner; D Ukena; H Schott; P J Funke; M Gramatzki; S Jürgenson; T Wandert; T Patzelt; M Reitz
Journal:  Br J Cancer       Date:  2001-10-19       Impact factor: 7.640

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  44 in total

Review 1.  Comparing how significantly the pharmacological treatment of genitourinary cancer in a non-curative setting affects endpoints of survival or response.

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2.  Antibody-based therapeutics to watch in 2011.

Authors:  Janice M Reichert
Journal:  MAbs       Date:  2011-01-01       Impact factor: 5.857

3.  An update on current management of advanced renal cell cancer, biomarkers, and future directions.

Authors:  Wanqing Iris Zhi; Jenny J Kim
Journal:  Ann Cancer Res       Date:  2014

4.  Dithiocarbamates strongly inhibit carbonic anhydrases and show antiglaucoma action in vivo.

Authors:  Fabrizio Carta; Mayank Aggarwal; Alfonso Maresca; Andrea Scozzafava; Robert McKenna; Emanuela Masini; Claudiu T Supuran
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Review 5.  How far is the horizon? From current targets to future drugs in advanced renal cancer.

Authors:  Stephan Kruck; Axel S Merseburger; Arnulf Stenzl; Jens Bedke
Journal:  World J Urol       Date:  2013-05-09       Impact factor: 4.226

6.  Systemic therapy for metastatic renal cell carcinoma: a review and update.

Authors:  Joshua E Logan; Edward N Rampersaud; Geoffrey A Sonn; Karim Chamie; Arie S Belldegrun; Allan J Pantuck; Dennis J Slamon; Fairooz F Kabbinavar
Journal:  Rev Urol       Date:  2012

7.  Depletion of carbonic anhydrase IX abrogates hypoxia-induced overexpression of stanniocalcin-1 in triple negative breast cancer cells.

Authors:  Elīna Zandberga; Pawel Zayakin; Artūrs Ābols; Dārta Pūpola; Pēteris Trapencieris; Aija Linē
Journal:  Cancer Biol Ther       Date:  2017-06-30       Impact factor: 4.742

Review 8.  Tumour acidosis: from the passenger to the driver's seat.

Authors:  Cyril Corbet; Olivier Feron
Journal:  Nat Rev Cancer       Date:  2017-09-15       Impact factor: 60.716

9.  Advances in Anti-Cancer Drug Development Targeting Carbonic Anhydrase IX and XII.

Authors:  Mam Y Mboge; Robert McKenna; Susan C Frost
Journal:  Top Anticancer Res       Date:  2015

10.  Relevance of cellular and serum carbonic anhydrase IX in primary breast cancer.

Authors:  Dina Schütze; Karin Milde-Langosch; Isabell Witzel; Achim Rody; Thomas Karn; Marcus Schmidt; Matthias Choschzick; Fritz Jänicke; Volkmar Müller
Journal:  J Cancer Res Clin Oncol       Date:  2013-01-29       Impact factor: 4.553

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