scholarly journals The Timing of Immunotherapy and Nephrectomy in Multimodality Treatment of Metastatic Renal Cell Carcinoma

2003 ◽  
Vol 2 (3) ◽  
pp. 205-210 ◽  
Author(s):  
Axel Bex ◽  
Simon Horenblas ◽  
Gijsbert C. de Gast

Multimodality treatment of metastatic renal cell carcinoma with immunotherapy and cytoreductive surgery is controversial. Especially the benefit of removing asymptomatic primary tumors in synchronous metastatic renal cell cancer has been debated since several non-randomized, retrospective studies revealed an improved response to immunotherapy and prolonged survival following initial nephrectomy. Two recent randomized prospective trials both demonstrated a prolonged survival in those who were randomly assigned to undergo nephrectomy of the primary tumor prior to treatment with interferon alfa-2b than in those who were assigned to undergo treatment with interferon alfa-2b alone. In these trials the survival benefit was limited and strongly influenced by overall performance score. The timing of immunotherapy, either as neoadjuvant (prior to nephrectomy) or adjuvant treatment (following nephrectomy) in the multimodality approach of synchronous metastatic renal cell carcinoma remains controversial. Selection of patients, the possible mechanisms underlying the survival advantage of the combination of nephrectomy and immunotherapy, and the timing of the treatment modalities are discussed herein.

Author(s):  
Christopher Weight

This chapter summarizes the findings of a landmark trial of cytoreductive nephrectomy in patients with metastatic renal cell carcinoma performed in the interferon era. All enrolled patients had a good performance status. It found overall survival extended by about 3 months in the cytoreductive-nephrectomy-plus-interferon arm versus the interferon-only arm.


2009 ◽  
Vol 48 (6) ◽  
pp. 901-908 ◽  
Author(s):  
David Lyrdal ◽  
Ulrika Stierner ◽  
Sven Lundstam

1995 ◽  
Vol 13 (2) ◽  
pp. 497-501 ◽  
Author(s):  
J Atzpodien ◽  
E Lopez Hänninen ◽  
H Kirchner ◽  
H Bodenstein ◽  
M Pfreundschuh ◽  
...  

PURPOSE In a phase II multiinstitutional outpatient trial, patients with progressive metastatic renal cell carcinoma were treated with a combination of subcutaneous (SC) recombinant interleukin-2 (rIL-2) and recombinant interferon alfa-2 (rIFN alpha 2). PATIENTS AND METHODS One hundred fifty-two patients with metastatic renal cell carcinoma were treated. Treatment courses consisted of SC rIL-2 at 20 x 10(6) IU/m2 three times per week in weeks 1 and 4, and at 5 x 10(6) IU/m2 three times per week in weeks 2, 3, 5, and 6. Additionally, patients received SC rIFN alpha 2 6 x 10(6) U/m2 once per week in weeks 1 and 4, and three times per week in weeks 2, 3, 5, and 6. RESULTS There were nine (6%) complete responses (CRs) and 29 (19%) partial responses (PRs), for an overall response rate of 25% (95% confidence interval, 19% to 32%). The median duration of responses for CRs and PRs was 16+ and 9 months, respectively. Additionally, 55 patients (36%) had stable disease (SD). Fifty-nine patients (39%) had continued disease progression (PD) despite treatment, or went off study after less than 4 weeks of therapy. The majority of patients treated experienced fever, chills, malaise, nausea, vomiting, and anorexia, side effects that were mostly limited to World Health Organization (WHO) grade 1 and 2. However, one patient developed grade 4 CNS toxicity with extended somnolence. On cessation of therapy, the neurologic symptoms in this patient were fully reversible, with no neurologic deficiency. CONCLUSION In summary, this multiinstitutional home-therapy setting of SC rIL-2 and SC rIFN alpha 2 in patients with progressive metastatic renal cell carcinoma demonstrated drastically reduced systemic toxicity, while it confirmed the therapeutic efficacy of the low-dose SC immunotherapy combination schedule.


1995 ◽  
Vol 13 (3) ◽  
pp. 688-696 ◽  
Author(s):  
G Fyfe ◽  
R I Fisher ◽  
S A Rosenberg ◽  
M Sznol ◽  
D R Parkinson ◽  
...  

PURPOSE To determine the efficacy and toxicity of a high-dose interleukin-2 (IL-2) regimen in patients with metastatic renal cell carcinoma. PATIENTS AND METHODS Two hundred fifty-five assessable patients were entered onto seven phase II clinical trials. Proleukin (aldesleukin; Chiron Corp, Emeryville, CA) 600,000 or 720,000 IU/kg was administered by 15-minute intravenous (i.v.) infusion every 8 hours for up to 14 consecutive doses over 5 days as clinically tolerated with maximum support, including pressors. A second identical cycle of treatment was scheduled following 5 to 9 days of rest, and courses could be repeated every 6 to 12 weeks in stable or responding patients. RESULTS The overall objective response rate was 14% (90% confidence interval [CI], 10% to 19%), with 12 (5%) complete responses (CRs) and 24 (9%) partial responses (PRs). Responses occurred in all sites of disease, including bone, intact primary tumors, and visceral metastases, and in patients with large tumor burdens or bulky individual lesions. The median response duration for patients who achieved a CR has not been reached, but was 19.0 months for those who achieved a PR. Baseline Eastern Cooperative Oncology Group (ECOG) performance status (PS) was the only predictive prognostic factor for response to IL-2. While treatment was associated with severe acute toxicities, these generally reversed rapidly after therapy was completed. However, 4% of patients died of adverse events judged to be possibly or probably treatment-related. CONCLUSION High-dose IL-2 appears to benefit some patients with metastatic renal cell carcinoma by producing durable CRs or PRs. Despite severe acute treatment-associated toxicities, IL-2 should be considered for initial therapy of patients with appropriately selected metastatic renal cell carcinoma.


2010 ◽  
Vol 28 (13) ◽  
pp. 2137-2143 ◽  
Author(s):  
Brian I. Rini ◽  
Susan Halabi ◽  
Jonathan E. Rosenberg ◽  
Walter M. Stadler ◽  
Daniel A. Vaena ◽  
...  

Purpose Bevacizumab is an antibody that binds vascular endothelial growth factor and has activity in metastatic renal cell carcinoma (RCC). Interferon alfa (IFN-α) is the historic standard initial treatment for RCC. A prospective, randomized, phase III trial of bevacizumab plus IFN-α versus IFN-α monotherapy was conducted. Patients and Methods Patients with previously untreated, metastatic clear cell RCC were randomly assigned to receive either bevacizumab (10 mg/kg intravenously every 2 weeks) plus IFN-α (9 million units subcutaneously three times weekly) or the same dose and schedule of IFN-α monotherapy in a multicenter phase III trial. The primary end point was overall survival (OS). Secondary end points were progression-free survival (PFS), objective response rate, and safety. Results Seven hundred thirty-two patients were enrolled. The median OS time was 18.3 months (95% CI, 16.5 to 22.5 months) for bevacizumab plus IFN-α and 17.4 months (95% CI, 14.4 to 20.0 months) for IFN-α monotherapy (unstratified log-rank P = .097). Adjusting on stratification factors, the hazard ratio was 0.86 (95% CI, 0.73 to 1.01; stratified log-rank P = .069) favoring bevacizumab plus IFN-α. There was significantly more grade 3 to 4 hypertension (HTN), anorexia, fatigue, and proteinuria for bevacizumab plus IFN-α. Patients who developed HTN on bevacizumab plus IFN-α had a significantly improved PFS and OS versus patients without HTN. Conclusion OS favored the bevacizumab plus IFN-α arm but did not meet the predefined criteria for significance. HTN may be a biomarker of outcome with bevacizumab plus IFN-α.


2007 ◽  
Vol 356 (2) ◽  
pp. 115-124 ◽  
Author(s):  
Robert J. Motzer ◽  
Thomas E. Hutson ◽  
Piotr Tomczak ◽  
M. Dror Michaelson ◽  
Ronald M. Bukowski ◽  
...  

Sign in / Sign up

Export Citation Format

Share Document