Sunitinib in Patients With Metastatic Renal Cell Carcinoma
Robert J. Motzer,Brian I. Rini,Brian I. Rini,Ronald M. Bukowski,Brendan D. Curti,Daniel J. George,Gary R. Hudes,Bruce G. Redman,Kim Margolin,Jaime R. Merchan,George Wilding,Michelle S. Ginsberg,Jennifer Bacik,Sindy T. Kim,Charles M. Baum,M. Dror Michaelson +15 more
Reads0
Chats0
TLDR
The results of this trial demonstrate the efficacy and manageable adverse-event profile of sunitinib as a single agent in second-line therapy for patients with cytokine-refractory metastatic clear-cell RCC.Abstract:
ContextCurrent treatment options for metastatic renal cell carcinoma (RCC) are limited and there is a need to identify novel and effective therapies. Sunitinib malate is an oral multitargeted tyrosine kinase inhibitor, which has shown activity in an initial study of cytokine-refractory metastatic RCC patients.ObjectiveTo confirm the antitumor efficacy of sunitinib as second-line treatment in patients with metastatic clear-cell RCC, the predominant cell type of this malignancy.Design, Setting, and PatientsOpen-label, single-arm, multicenter clinical trial. Patients were enrolled between February and November 2004, with follow-up continuing until disease progression, unacceptable toxicity, or withdrawal of consent. The reported data apply through August 2005. Patients (N = 106) had metastatic clear-cell RCC, which had progressed despite previous cytokine therapy.InterventionRepeated 6-week cycles of sunitinib, 50 mg per day given orally for 4 consecutive weeks followed by 2 weeks off per treatment cycle.Main Outcome MeasuresAssessment of clinical response, degree of tumor regression on imaging studies using the Response Evaluation Criteria in Solid Tumors (RECIST) guidelines. Primary end point was overall objective response rate (complete plus partial). Secondary end points were progression-free survival and safety. Response was evaluated by independent third-party core imaging laboratory and by treating physicians (investigator assessment).ResultsAll 106 patients received sunitinib and were included in the intent-to-treat population for safety analyses. Of these, 105 patients were evaluable for efficacy analyses. The objective response rate according to an independent third-party assessment resulted in 36 patients with partial response (34%; 95% confidence interval, 25%-44%), and a median progression-free survival of 8.3 months (95% confidence interval, 7.8-14.5 months). The most common adverse events experienced by patients were fatigue in 30 (28%) and diarrhea 21 (20%). Neutropenia, elevation of lipase, and anemia were the most common laboratory abnormalities observed in 45 (42%), 30 (28%), and 27 (26%) patients, respectively.ConclusionThe results of this trial demonstrate the efficacy and manageable adverse-event profile of sunitinib as a single agent in second-line therapy for patients with cytokine-refractory metastatic clear-cell RCC.Trial Registrationclinicaltrials.gov Identifier: NCT00077974read more
Citations
More filters
Journal ArticleDOI
Sunitinib versus interferon alfa in metastatic renal-cell carcinoma.
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 Bycott,Charles M. Baum,Robert A. Figlin +13 more
TL;DR: Progression-free survival was longer and response rates were higher in patients with metastatic renal-cell cancer who received sunitinib than in those receiving interferon alfa.
Journal ArticleDOI
Sorafenib in advanced clear-cell renal-cell carcinoma.
Bernard Escudier,Tim Eisen,Walter M. Stadler,Cezary Szczylik,Stéphane Oudard,Michael Siebels,Sylvie Negrier,Christine Chevreau,Ewa Solska,Apurva A. Desai,Frederic Rolland,Tomasz Demkow,Thomas E. Hutson,Martin Gore,Scott Freeman,Brian Schwartz,M. Shan,Ronit Simantov,Ronald M. Bukowski +18 more
TL;DR: As compared with placebo, treatment with sorafenib prolongs progression-free survival in patients with advanced clear-cell renal-cell carcinoma in whom previous therapy has failed; however, treatment is associated with increased toxic effects.
Journal ArticleDOI
Bevacizumab plus interferon alfa-2a for treatment of metastatic renal cell carcinoma: a randomised, double-blind phase III trial
Bernard Escudier,Anna Pluzanska,Piotr Koralewski,Alain Ravaud,Sergio Bracarda,Cezary Szczylik,Christine Chevreau,Marek Filipek,Bohuslav Melichar,Emilio Bajetta,Vera Gorbunova,Jacques-Olivier Bay,Istvan Bodrogi,Agnieszka Jagiełło-Gruszfeld,Nicola Moore +14 more
TL;DR: In this article, the authors investigated the combination treatment of the humanised anti-VEGF monoclonal antibody bevacizumab with interferon alfa, and reported a significant improvement in progression-free survival.
Journal ArticleDOI
Overall Survival and Updated Results for Sunitinib Compared With Interferon Alfa in Patients With Metastatic Renal Cell Carcinoma
Robert J. Motzer,Thomas E. Hutson,Piotr Tomczak,M. Dror Michaelson,Ronald M. Bukowski,Stéphane Oudard,Sylvie Negrier,Cezary Szczylik,Roberto Pili,Georg A. Bjarnason,Xavier Garcia-del-Muro,Jeffrey A. Sosman,Ewa Solska,George Wilding,John A. Thompson,Sindy T. Kim,Isan Chen,Xin Huang,Robert A. Figlin +18 more
TL;DR: Sunitinib demonstrates longer overall survival compared with IFN-alpha plus improvement in response and progression-free survival in the first-line treatment of patients with metastatic RCC, highlighting an improved prognosis in patients with RCC in the era of targeted therapy.
NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines
TL;DR: Lymphedema is a common complication after treatment for breast cancer and factors associated with increased risk of lymphedEMA include extent of axillary surgery, axillary radiation, infection, and patient obesity.
References
More filters
Book ChapterDOI
Nonparametric Estimation from Incomplete Observations
Edward L. Kaplan,Paul Meier +1 more
TL;DR: In this article, the product-limit (PL) estimator was proposed to estimate the proportion of items in the population whose lifetimes would exceed t (in the absence of such losses), without making any assumption about the form of the function P(t).
Journal ArticleDOI
New Guidelines to Evaluate the Response to Treatment in Solid Tumors
Patrick Therasse,Susan G. Arbuck,Elizabeth Eisenhauer,Jantien Wanders,Richard Kaplan,Larry Rubinstein,Jaap Verweij,Martine Van Glabbeke,Allan T. van Oosterom,Michaele C. Christian,S. Gwyther +10 more
TL;DR: A model by which a combined assessment of all existing lesions, characterized by target lesions and nontarget lesions, is used to extrapolate an overall response to treatment is proposed, which is largely validated by the Response Evaluation Criteria in Solid Tumors Group and integrated into the present guidelines.
Journal ArticleDOI
Activating mutations in the epidermal growth factor receptor underlying responsiveness of non-small-cell lung cancer to gefitinib
Thomas J. Lynch,Daphne W. Bell,Raffaella Sordella,Sarada Gurubhagavatula,Ross A. Okimoto,Brian W. Brannigan,Patricia L. Harris,Sara M. Haserlat,Jeffrey G. Supko,Frank G. Haluska,David N. Louis,David C. Christiani,Jeff Settleman,Daniel A. Haber +13 more
TL;DR: A subgroup of patients with non-small-cell lung cancer have specific mutations in the EGFR gene which correlate with clinical responsiveness to the tyrosine kinase inhibitor gefitinib, and these mutations lead to increased growth factor signaling and confer susceptibility to the inhibitor.
Journal ArticleDOI
Efficacy and safety of imatinib mesylate in advanced gastrointestinal stromal tumors.
George D. Demetri,Margaret von Mehren,Charles D. Blanke,Annick D. Van den Abbeele,Burton L. Eisenberg,Peter J. Roberts,Michael Heinrich,David A. Tuveson,Samuel Singer,Milos J. Janicek,Jonathan A. Fletcher,Stuart G. Silverman,Sandra Silberman,Renaud Capdeville,Beate Kiese,Bin Peng,Sasa Dimitrijevic,Brian J. Druker,Christopher L. Corless,Christopher D.M. Fletcher,Heikki Joensuu +20 more
TL;DR: Imatinib induced a sustained objective response in more than half of patients with an advanced unresectable or metastatic gastrointestinal stromal tumor, indicating that inhibition of the KIT signal-transduction pathway is a promising treatment for advanced gastrointestinalStromal tumors, which resist conventional chemotherapy.
Journal ArticleDOI
New guidelines to evaluate the response to treatment in solid tumors
Patrick Therasse,Susan G. Arbuck,Elizabeth Eisenhauer,Jantien Wanders,Richard Kaplan,Larry Rubinstein,Jaap Verweij,Martine Van Glabbeke,Allan T. van Oosterom,Michaele C. Christian,S. Gwyther +10 more
TL;DR: In this article, the authors proposed a model by which a combined assessment of all existing lesions, characterized by target lesions (to be measured) and nontarget lesions, is used to extrapolate an overall response to treatment.
Related Papers (5)
Sorafenib in advanced clear-cell renal-cell carcinoma.
Temsirolimus, interferon alfa, or both for advanced renal-cell carcinoma.
Gary R. Hudes,Michael A. Carducci,Piotr Tomczak,Janice P. Dutcher,Robert A. Figlin,Anil Kapoor,Elzbieta Staroslawska,Jeffrey A. Sosman,David F. McDermott,Istvan Bodrogi,Zoran Kovacevic,Vladimir Lesovoy,Ingo G.H. Schmidt-Wolf,Olga Barbarash,Erhan Gokmen,Timothy O'Toole,Stephanie Lustgarten,Laurence Moore,Robert J. Motzer +18 more