Immunotherapy of metastatic renal cell cancer

Goey, S.H.; Verweij, Jaap; Stoter, G.

doi:10.1093/oxfordjournals.annonc.a010790

Cited by 20 publications

(8 citation statements)

References 174 publications

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“…Attempting to compare results of types of treatment by such pooling of results is more treacherous, but was not the object of this study. The limited observations we draw in this regard are in accord with known trends [1, 2, 3, 4]. Regarding the increased responses of older patients, there was some uncertainty of this calculation arising from the lack of knowledge of patients’ dates of birth.…”

Section: Discussionmentioning

confidence: 58%

“…The management of advanced renal cell carcinoma (RCCa) continues as one of the most challenging problems facing oncologists [1, 2, 3, 4, 5]. Although this is usually a deadly condition, clinicians have been tantalized by reports of major and durable remissions induced by interleukin-2 (IL-2), as a stimulator of activated (i.e.…”

Section: Introductionmentioning

confidence: 99%

“…‘LAK’) cells, as a single agent or in combination. Given the general refractoriness of RCCa to cytotoxic chemotherapy [5], immunomodulation, as exemplified by IL-2-based regimens [2, 3, 4], appears to be the most promising paradigm for future progress. Although it is important to define factors associated with optimal results, the low incidence of responses has made it difficult to draw detailed conclusions from individual studies.…”

Section: Introductionmentioning

confidence: 99%

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A Literature Analysis of Prognostic Factors for Response and Quality of Response of Patients with Renal Cell Carcinoma to Interleukin-2-Based Therapy

Elias

Hunt²

2001

Oncology

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Objective: To characterize prognostic factors for response of advanced renal cell carcinoma to interleukin-2-based regimens. Patients and Methods: Data compiled from 80 published series were examined for associations between patient characteristics and outcomes. Results: Response rates were highest in trials utilizing interleukin-2 combinations. Longer median survivals were associated with high percentages of patients with nephrectomy, good performance status, with publication year, response rates, and inversely with median ages. Associations of performance status and prior nephrectomy with response rates were detected in trials with individual patient details. The response rate was higher for patients older than the median age of patients entering each trial, and also higher for males. Among responders, attainment of complete response was associated with fewer sites of involvement. Pooled response duration of patients reported to have complete responses exhibited durability, but no correlation with prognostic factors. Selection factors may have influenced apparent differences between types of regimens. We confirm the potential for durable remissions from interleukin-2-based regimens.

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Section: Discussionmentioning

confidence: 58%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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A Literature Analysis of Prognostic Factors for Response and Quality of Response of Patients with Renal Cell Carcinoma to Interleukin-2-Based Therapy

Elias

Hunt²

2001

Oncology

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“…Renal cancer is notoriously chemotherapy resistant. During the 1980th biological therapy with interferon with few responses, but considerable toxicity, was introduced and in the 1990th also IL2 was added, again with modest efficacy but with significant side effects [11]. Due to the frequently very slow disease progression with few symptoms (as in this case), many oncologists in the Scandinavian countries preferred expectation.…”

Section: Methodsmentioning

confidence: 99%

A new method to estimate parameters of the growth model for metastatic tumours

Mehrara

Forssell-Aronsson

Johanson

et al. 2013

Theor Biol Med Model

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PurposeKnowledge of natural tumour growth is valuable for understanding tumour biology, optimising screening programs, prognostication, optimal scheduling of chemotherapy, and assessing tumour spread. However, mathematical modelling in individuals is hampered by the limited data available. We aimed to develop a method to estimate parameters of the growth model and formation rate of metastases in individual patients.Materials and methodsData from one patient with liver metastases from a primary ileum carcinoid and one patient with lung metastases from a primary renal cell carcinoma were used to demonstrate this new method. Metastatic growth models were estimated by direct curve fitting, as well as with the new proposed method based on the relationship between tumour growth rate and tumour volume. The new model was derived from the Gompertzian growth model by eliminating the time factor (age of metastases), which made it possible to perform the calculations using data from all metastases in each patient. Finally, the formation time of each metastasis and, consecutively, the formation rate of metastases in each patient were estimated.ResultsWith limited measurements in clinical studies, fitting different growth curves was insufficient to estimate true tumour growth, even if patients were followed for several years. Growth of liver metastases was well described with a general growth model for all metastases. However, the lung metastases from renal cell carcinoma were better described by heterogeneous exponential growth with various growth rates.ConclusionAnalysis of the regression of tumour growth rate with the logarithm of tumour volume can be used to estimate parameters of the tumour growth model and metastasis formation rates, and therefore the number and size distribution of metastases in individuals.

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“…Drugs with some activity but no proven survival benefit are vinblastine, 5-fluoruracil (5-FU) and gemcitabine [9]. Interferon (IFN)-α offers in a small but significant percentage of patients advantage in overall survival [10][11][12][13]. Interleukin (IL)-2-based therapy gives similar survival rates although the only reported long-term remissions have been achieved with high-dose IL-2 [14][15][16][17][18][19][20][21][22].…”

Section: Introductionmentioning

confidence: 99%

Targeted Approaches for Treating Advanced Clear Cell Renal Carcinoma

Spronsen¹,

Mulder²

2006

Oncol Res Treat

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The mainstay of any curative treatment in renal cell carcinoma (RCC) is surgery. In the case of metastatic disease at presentation, a radical nephrectomy is recommended to good performance status patients prior to the start of cytokine treatment. Interferon (IFN)-a offers in a small but significant percentage of patients advantage in overall survival. Interleukin (IL)-2-based therapy gives similar survival rates. To date, hormonal therapy and chemotherapy do not have a proven impact on survival. Recent insights demonstrate that the majority of clear cell RCC harbor abnormalities of the von Hippel-Lindau (VHL) gene. This gene plays a key role in the stimulation of angiogenesis by vascular endothelial growth factor (VEGF) in this highly vascularized tumor. This opens interesting new treatment strategies including blockade of VEGF with the monoclonal antibody bevacizumab (Avastin?) and inhibition of VEGF receptor tyrosine kinases with small oral molecules such as sunitinib (SU11248, Sutent?) or PTK787. Likewise, inhibition of the Raf kinase pathway with oral sorafenib (Bay 43-9006, Nexavar?) or inhibition of the mTOR pathway with intravenous CCI-779 are under investigation. Preliminary clinical results with all these compounds are promising, and the results of ongoing first-line phase III studies will become available in the next years.

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Immunotherapy of metastatic renal cell cancer

Cited by 20 publications

References 174 publications

A Literature Analysis of Prognostic Factors for Response and Quality of Response of Patients with Renal Cell Carcinoma to Interleukin-2-Based Therapy

A Literature Analysis of Prognostic Factors for Response and Quality of Response of Patients with Renal Cell Carcinoma to Interleukin-2-Based Therapy

A new method to estimate parameters of the growth model for metastatic tumours

Targeted Approaches for Treating Advanced Clear Cell Renal Carcinoma

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