Low-dose γ-interferon therapy is ineffective in renal cell carcinoma patients with large tumour burden

Lerche, J; Thews, Anne; Lüttichau, Irene von; Jacobi, Nicole; Herold, Manfred; Aulitzky, Walter E.; Peschel, Christian; Stöckle, Michael; Huber, Christoph

doi:10.1016/0959-8049(94)90119-8

Cited by 13 publications

(6 citation statements)

References 19 publications

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“…Doberauer et al [20] observed only SD in 14 out of 20 patients with a treatment reg imen of lxlO6 IU IFN/m2 s.c. for 5 days every 5th week or 2x 106 IU IFN/nr s.c. once every 2nd week. A recent paper by Aulitzky et al demonstrates that the tumour burden influences the outcome of IFN-gamma therapy as well [29]. The administered IFN-gamma activated the immune system since significant increases in cellular and humoral measures were observed for the 6-month values compared to values prior to treatment.…”

Section: Discussionmentioning

confidence: 99%

Immunomonitoring in Treatment of Metastatic Renal Cell Carcinoma with Interferon Gamma

Goepel¹,

Otto²,

Möllhoff³

et al. 1995

Oncol Res Treat

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Background: Metastatic renal cancer is considered not to benefit from treatment by present-day methods. Clinical and experimental experience lead to the suggestion that mechanisms exerted by the immune system favour the outcome of patients with metastatic renal carcinoma. Immunomodulating therapy with interferon-gamma has been proved to be clinically effective in etastatic renal carcinoma. Material and Methods: A non-randomized phase-II study was initiated to observe the clinical and immunological effects of 200 μg interferon-gamma (IFN-gamma) s. c. once weekly in patients with metastatic renal carcinoma. Twenty patients were enrolled in this study. The protocol was accepted by the Ethical Committee of the Medical Faculty, University of Essen. Clinical data, cellular and humoral immune system parameters were monitored over 6 months. Results: Median survival of the patients was 12 months. No complete or partial remission could be documented. We observed a significant increase in lymphocyte, B, T, T helper and natural killer (NK) cell counts after 6 months of treatment compared to the appropriate pretreatment values. Concentrations of complement C3, C4 and immunoglobulins (Ig) A, IgG and IgM were also significantly increased after treatment with IFN-gamma. Pretreatment values of B, T, T helper and NK cells were decreased and complement serum values were increased in comparison to normal values. Conclusion: Although a significant increase of the investigated immunologie parameters after IFN-gamma therapy could be seen, no clinical remission was associated with this treatment modality. The validity and usefulness of immunomonitoring in metastatic renal cancer has to be discussed again.

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Section: Discussionmentioning

confidence: 99%

Immunomonitoring in Treatment of Metastatic Renal Cell Carcinoma with Interferon Gamma

Goepel¹,

Otto²,

Möllhoff³

et al. 1995

Oncol Res Treat

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“…A relationship between an impaired bio logical response to BRM's and clinical resistance to immuno therapy has been reported [15,21]. However, many patients do not respond to therapy in spite of induction of a normal bio logical response [17,22]. Therefore it seems unlikely that pri mary resistance to immunotherapy is preferentially caused by an impaired biological response.…”

Section: Discussionmentioning

confidence: 99%

“…Data from 3 published intermittent low-dose IFN gamma studies and those from an Austrian ongoing multicenter trial and an unpublished phase II trial at the University of Heidelberg are retrospectively analyzed [15][16][17]. All centers were asked to provide the data of all patients treated according to this schedule.…”

Section: Methodsmentioning

confidence: 99%

“…Clinical efficacy of intermittent therapy with nontoxic low-doses of IFN gamma was recently shown in 2 clinical phase II trials [15,16], However, limited antitumor efficacy was observed in a 3rd trial testing a similar low-dose IFN gamma therapy at our institution [17]. All 3 studied applied a low-dose of rIFN gamma once weekly for long-term treatment of patients suffering from advanced RCC.…”

Section: Introductionmentioning

confidence: 99%

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Intermittent Low-Dose IFN Gamma Treatment for Metastatic Renal Cell Carcinoma: Analysis of Factors Predicting Clinical Response and Long-Term Survival

Aulitzky

Aulitzky²,

Ellerhorst

et al. 1995

Oncol Res Treat

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Background: Objective tumor remissions are induced by a variety of immunomodulating agents in a minority of patients suffering from metastasizing renal cell carcinoma. The results of different clinical studies, however, varied greatly for each of these treatment modalities. In order to elucidate potential causes for this variability and to further study the long-term results of intermittent low-dose IFN gamma therapy in patients with advanced renal cell cancer (RCC) we retrospectively analyzed factors predicting clinical response and long-term survival of 121 patients. Material and Methods: We retrospectively analyzed the clinical results of 5 phase II studies treating 121 patients with intermittent low-dose IFN gamma as first-line treatment for metastatic RCC. Results: 15% complete and partial responses were observed in these patients. Intermittent low-dose IFN gamma was well-tolerated and treatment was performed largely on an outpatient basis. Clinical presentation of the disease was the only factor predicting both clinical response and survival. Whereas a 23% response rate was observed in patients suffering from limited disease RCC (disease limited to one site including adjacent lymph nodes), the response rate in patients with widespread disease was less than 5%. When the results of the 5 studies were compared, a statistically highly significant correlation between the proportion of treated patients with limited disease and response rate was observed. Conclusion: We conclude that intermittent low-dose IFN gamma is effective and induced long-term complete remissions in a proportion of patients with limited disease metastatic RCC.

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“…The response rate for IFN‐α is 5–26% [ 12–19] and for IFN‐γ is 0–30% [ 16, 20–23]. The response rate for their combination, based on the proposed synergism of these agents, is 4–27% [ 16, 18, 24–26].…”

Section: Introductionmentioning

confidence: 99%

Preliminary results of the alternating administration of natural interferon‐α and recombinant interferon‐γ for metastatic renal cell carcinoma

et al. 1999

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Objective To evaluate the eBcacy and toxicity of the median and maximum time to remission in the responders were 2 and 7 months, respectively. The alternating administration of natural (n) interferon (IFN)-a and recombinant (r) IFN-c for metastatic RCC.survival time of the responders was significantly longer than that of those not responding (stable and progressPatients and methods The study comprised 24 patients (median age 60 years, range 42-77), 20 of whom ive disease, P=0.0202). Toxicities were mostly limited to WHO grades 1 and 2, with grade 3 leucopenia and were evaluable for response and all 24 evaluable for toxicity. Initially, nIFN-a was administered subcutanegrade 4 hepatic dysfunction in only one patient each. These toxicities were transient and there were no ously on days 1 and 3, and rIFN-c on day 2, for 1-2 weeks in the evening or at night, both at doses treatment-related deaths. Conclusion The alternating administration of nIFN-a and of 3 MU. If this regimen was tolerated, nIFN-a and rIFN-c were administered at the same doses on days rIFN-c is an eCective treatment for metastatic RCC. This treatment is particularly suitable for patients who 1, 3 and 5, and on days 2 and 4, respectively. Results There were three complete remissions and two have undergone nephrectomy and have lung metastases. partial remissions, giving a total response rate of 25%. All responders (complete plus partial remission) had Keywords Renal cell carcinoma, immunotherapy, IFN-a, IFN-c combination therapy undergone nephrectomy. Multiple lung metastases completely disappeared from four responders. The [5,6]. These two IFNs have diCerent receptors on the cell

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Low-dose γ-interferon therapy is ineffective in renal cell carcinoma patients with large tumour burden

Cited by 13 publications

References 19 publications

Immunomonitoring in Treatment of Metastatic Renal Cell Carcinoma with Interferon Gamma

Immunomonitoring in Treatment of Metastatic Renal Cell Carcinoma with Interferon Gamma

Intermittent Low-Dose IFN Gamma Treatment for Metastatic Renal Cell Carcinoma: Analysis of Factors Predicting Clinical Response and Long-Term Survival

Preliminary results of the alternating administration of natural interferon‐α and recombinant interferon‐γ for metastatic renal cell carcinoma

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