Radical nephrectomy plus interferon-alfa-based immunotherapy compared with interferon alfa alone in metastatic renal-cell carcinoma: a randomised trial

Mickisch, G.; Garin, A.; Poppel, Hendrik Van; Prijck, Linda de; Sylvester, Richard

doi:10.1016/s0140-6736(01)06103-7

Cited by 1,312 publications

(713 citation statements)

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“…The current standard of care is cytoreductive nephrectomy followed by vascular endothelial growth factor (VEGF) tyrosine kinase inhibitors (TKI) 1 . The use of nephrectomy in metastatic disease was established prior to the development of VEGF TKIs 2,3 . This sequence has not been prospectively evaluated in the era of VEGF targeted therapy, although large recent retrospective series suggest nephrectomy is still associated with a survival benefit in unselected patients 4 .…”

Section: Introductionmentioning

confidence: 99%

Safety and Efficacy of Pazopanib Therapy Prior to Planned Nephrectomy in Metastatic Clear Cell Renal Cancer

et al. 2016

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Section: Introductionmentioning

confidence: 99%

Safety and Efficacy of Pazopanib Therapy Prior to Planned Nephrectomy in Metastatic Clear Cell Renal Cancer

et al. 2016

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“…The median survival was 17 months in the CRN + IFN-a2b group as against to 7 months in the IFN-a2b group, with 1-year survival of 59.3 versus 33.7%, respectively, with a hazard ratio (95% CI) of 0.54 (0.31-0.94) [7].…”

Section: Discussionmentioning

confidence: 96%

“…However, many people felt that the results were achieved due to selection bias while some felt that CRN could have some biological effect on patient survival. The EORTC in their study-EORTC 30947-and the SWOG in their study-SWOG 8949-studied the issue of CRN with immunotherapy versus immunotherapy alone by using IFN-a2b [7,8]. Both trials recruited histologically confirmed clear cell mRCC with metastases beyond regional lymphatics, absence of brain metastases, inferior vena cava (IVC) thrombus below hepatic veins, if present.…”

Section: Discussionmentioning

confidence: 99%

“…Interferon alpha 2-b was considered safer than interleukin-2; the latter had high toxicity profile, had to be administered in the hospital setting, and was costly. Two major randomised controlled trials (European Organisation for Research and Treatment of Cancer (EORTC) 30947 and Southwest Oncology Group (SWOG) 8949) and their combined analysis showed significant survival benefit when patients with metastatic RCC (mRCC) were treated with cytoreductive nephrectomy and interferon alpha 2-b versus interferon alpha 2-b alone [7][8][9].…”

Section: Introductionmentioning

confidence: 99%

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Cytoreductive Surgery in the Management of Renal Tumours: Rationale, Current Evidence and Future Perspectives

Khochikar

2016

Indian J Surg Oncol

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Renal cell carcinoma accounts for 3% of adult solid malignant tumours. Approximately 25% of the patients present with metastatic disease at presentation. In the era of immunotherapy (interferon alpha-2b and interleukin-2), studies showed significant survival benefit with cytoreductive nephrectomy (CRN) followed by interferon alpha-2b than interferon alpha 2-b alone. Introduction of targeted therapies (vascular endothelial growth factor receptor-tyrosine kinase inhibitors, mammalian target of rapamycin inhibitors) in 2005 generated a great interest in the management of metastatic renal cell carcinoma (mRCC) as these drugs exhibited tumour shrinkage in the primary tumour as well as in the metastatic site/s. Though there is no level 1 evidence, many studies have shown the usefulness of cytoreductive nephrectomy along with targeted therapy as against to targeted therapy alone. This review is aimed at the rationale behind the cytoreductive nephrectomy in mRCC, the current evidence and what is in store for the future. A detailed search on the management of mRCC was carried out on MEDLINE, Embase, CANCERLIT and Cochrane Library databases using the key words Bcytoreductive nephrectomy^, Bimmunotherapy^and Btargeted therapy^since 1980 till 2015. Original articles, review articles, monograms, book chapters on metastatic renal cancer and textbooks on urologic oncology, oncology and urology were reviewed. Various international guidelines on this issue were also studied. An identical search was performed using the American Society of Clinical Oncology Abstract database. Trials in the progress or recently completed that were relevant to this paper were identified through clinicaltrials.gov. The latest information for new articles ahead of publication was last accessed in November 2015. CRN has remained an integral part to the management of metastatic renal cell carcinoma mainly for the patients with good performance status, life expectancy of more than 12 months and in the absence of adverse prognostic factors. It had shown measurable survival benefit in the era of immunotherapy (CRN + immunotherapy vs. immunotherapy alone). In the era of targeted therapy, many studies have shown significant survival benefit with CRN + targeted therapy. However, there is no clear level 1 evidence to support this. The ongoing trials (CARMENA and European Organisation for Research and Treatment of Cancer SURTIME) would perhaps guide us in the way in which we should manage mRCC disease in the future. Maybe we may find some answers on the issues of the effectiveness of targeted therapy, the timing of CRN and sequencing these treatment arms once the results of these ongoing and future trials are through.

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“…Two large studies showed that tumour nephrectomy followed by immunotherapy results in longer survival of patients with metastatic renal cell cancer (Flanigan et al, 2001;Mickisch et al, 2001). In our study, no adjuvant immunotherapy was administered, and only five of 16 patients with metastasised (stage IV) RCC received systemic immunotherapy according to departmental guidelines at the time of the trial.…”

Section: Discussionmentioning

confidence: 99%

Perioperative immunomodulation with interleukin-2 in patients with renal cell carcinoma: results of a controlled phase II trial

Klatte

Ittenson

et al. 2006

Br J Cancer

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We conducted a non-randomised controlled phase II trial to investigate the role of preoperative administration of interleukin-2 (IL-2) in patients with renal cell carcinoma undergoing tumour nephrectomy. A total of 120 consecutive patients were allocated alternately to the two study groups: perioperative immunomodulation with IL-2 (IL-2 group; n ¼ 60) and perioperative immunomonitoring without immunomodulation (control group; n ¼ 60). Patients from the IL-2 group received four doses of 10 Â 10 6 IU m À2 twice daily subcutaneously a week before operation followed by a daily maintenance dose of 3 Â 10 6 IU m À2 subcutaneously until a day before the operation. Parameters of cellular and humoral immunity (leucocytes, T-cell markers CD3, CD4, and CD8, B-cell marker CD19, monocyte marker CD14, natural killer (NK) cell markers CD16, CD56, and CD57, activation markers CD6, CD25, CD28, and CD69, progenitor cell marker CD34, as well as IL-2, IL-6, IL-10, soluble IL-2 receptor, IL-1 receptor antagonist, transforming growth factorb1, and vascular endothelial growth factor) were measured in peripheral venous blood at various intervals. Interleukin-2-related toxicity was WHO grade 1 (24%), 2 (67%), and 3 (9%). In the postoperative period, T-cell markers, activation markers, and NK cell markers decreased, and IL-6 and IL-10 increased. However, all these alterations were significantly less accentuated in patients who had been pretreated with IL-2. Median follow-up was 40 months. Tumour-specific survival in the IL-2 group and the control group was 98 vs 81% after 1 year and 86 vs 73% after 5 years (P ¼ 0.04). A similar effect was found for progression-free survival. We conclude that IL-2 can be safely administered in the perioperative period and modulates immunological parameters. However, to validate the survival data, a larger randomised phase III trial is needed.

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Radical nephrectomy plus interferon-alfa-based immunotherapy compared with interferon alfa alone in metastatic renal-cell carcinoma: a randomised trial

Cited by 1,312 publications

References 11 publications

Safety and Efficacy of Pazopanib Therapy Prior to Planned Nephrectomy in Metastatic Clear Cell Renal Cancer

Safety and Efficacy of Pazopanib Therapy Prior to Planned Nephrectomy in Metastatic Clear Cell Renal Cancer

Cytoreductive Surgery in the Management of Renal Tumours: Rationale, Current Evidence and Future Perspectives

Perioperative immunomodulation with interleukin-2 in patients with renal cell carcinoma: results of a controlled phase II trial

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