Phase II Study of Interferon-gamma Versus Interleukin-2 and Interferon-alpha 2b in Metastatic Renal Cell Carcinoma

Lümmen, G.; Goepel, Μ.; Möllhoff, Stefan; Hinke, Axel; Otto, T.; Rübben, H.

doi:10.1016/s0022-5347(01)66417-6

Cited by 26 publications

(13 citation statements)

References 17 publications

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“…[10][11][12][13][14][15][16] We excluded 1 of the 7 eligible trials because most of the patients (58%) were lost to follow-up. 11 All 6 trials were published as full reports in journals.…”

Section: Literature Search Resultsmentioning

confidence: 99%

“…Objective response rate was designated the primary outcome in 4 trials 10,12,13,15 and was reported in 5 trials 10,12,13,15,16 (Table 2). Overall survival and progression-free survival data were reported in 6 and 4 trials, 10,12,13,15 respectively (Table 2).…”

Section: Discussionmentioning

confidence: 99%

“…Only 3 trials provided statistical comparisons of those data 10,15,16 ; 2 trials (3 comparisons) reported statistically significant higher response rates with IL-2. …”

Section: Objective Response Ratementioning

confidence: 99%

“…There were three 3-arm trials 10,13,15 and three 2-arm trials. 12,14,16 Across these trials, 1098 eligible patients were randomized, with patient accruals per trial ranging from 60 to 425. None of the trials were placebocontrolled.…”

Section: Randomized Controlled Trials Trial Characteristicsmentioning

confidence: 99%

“…None of the trials were placebocontrolled. All of the trials assessed IL-2 in combination with other agents, and 2 of the 3-arm trials also included a single-agent IL-2 arm.13,15 IL-2 was studied in combination with IFN-a (2a or 2b) in each trial, either alone 13,15,16 or with 5-fluorouracil (5-FU) 10,12 or 5-FU and 13-cis retinoic acid (13cRA) 10 or tamoxifen.14 The doses and route of administration of IL-2 differed significantly between trials. Four trials evaluated IL-2 given subcutaneously (2 at a low dose of 2.4 to 4.8 mu/m 2 ), and 2 trials evaluated IL-2 administered intravenously at a dose of 18 mu/m 2 .…”

mentioning

confidence: 99%

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Interleukin-2 in the treatment of unresectable or metastatic renal cell cancer: a systematic review and practice guideline

Hotte

Waldron

Canil

et al. 2012

CUAJ

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Objective: We performed a systematic review of randomized controlled trials (RCTs) to assess the efficacy of interleukin-2 (IL-2) for the treatment of patients with unresectable or metastatic renal cell carcinoma (RCC). Methods:We searched the literature to identify RCTs or meta-analyses of RCTs comparing treatment regimens with IL-2 to those without. Outcomes of interest included overall or progression-free survival, response rate, toxicity and quality of life. Results:We identified 36 RCTs, and 6 met the eligibility criteria (1098 patients).We studied IL-2 alone and in combination with other agents, including interferon-alpha (IFN-a), 5-fluorouracil (5-FU), and 13-cis-retinoic acid or tamoxifen. No trials comparing high-dose IL-2 to non-IL-2 regimens were identified. A meta-analysis of 1-year mortality data from the 6 trials did not show a difference between IL-2-based regimens and non-IL-2 controls. Two of the 6 trials detected statistically significant longer survival with IL-2 combined with IFN-a and 5-FU. Of the 4 trials that assessed progression-free survival, 3 reported significantly longer progression-free intervals with IL-2-based regimens. Five trials reported response rates; pooling the rates from these trials gave an overall weighted response rate of 13.3% (range 9%-39%) and 5.3% (range 0%-20%) for IL-2-containing regimens and non-IL-2 regimens, respectively. IL-2-based regimens were more toxic than were non-IL-2 controls; the most frequently reported grade 3-4 toxicities were hypotension (range 6%-68%), fever (2%-56%), nausea or vomiting or both (6%-34%), diarrhea (1%-28%) and cardiac toxicity (11%-25%). None of the trials reported healthrelated quality-of-life data. Conclusion:Non-high-dose IL-2 containing regimens do not provide superior treatment efficacy over non-IL-2-based regimens, with added toxicity, and therefore should not be used as standard treatment for patients with unresectable or metastatic RCC. High-dose IL-2 should only be used by experienced physicians in the context of a clinical trial or investigative setting. R enal cell carcinomas (RCCs) account for 3% of all adult solid malignancies. 1 In 2006, it was estimated that 4600 patients would be diagnosed with the disease in Canada.2 According to Bukowski, at the time of first diagnosis, 45% of patients will present with local- without an IL-2 arm. IL-2 was also approved by Health Canada in 2003, but its use has been very sporadic and limited. Because interferon-alpha (IFN-a) is associated with a real, if modest, survival benefit in the randomized setting 6 and because it is accessible to and tolerated by most RCC patients, it has become a de facto standard of care in Canada.To clarify the role of IL-2 in the treatment of RCC and to develop appropriate recommendations for treatment, the Genitourinary Cancer Disease Site Group (GU DSG) of Cancer Care Ontario's Program in Evidence-based Care (PEBC) systematically reviewed evidence from randomized controlled trials (RCTs) of IL-2 in patients with unresectable or metastatic RCC...

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“…[10][11][12][13][14][15][16] We excluded 1 of the 7 eligible trials because most of the patients (58%) were lost to follow-up. 11 All 6 trials were published as full reports in journals.…”

Section: Literature Search Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

“…Only 3 trials provided statistical comparisons of those data 10,15,16 ; 2 trials (3 comparisons) reported statistically significant higher response rates with IL-2. …”

Section: Objective Response Ratementioning

confidence: 99%

Section: Randomized Controlled Trials Trial Characteristicsmentioning

confidence: 99%

mentioning

confidence: 99%

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Interleukin-2 in the treatment of unresectable or metastatic renal cell cancer: a systematic review and practice guideline

Hotte

Waldron

Canil

et al. 2012

CUAJ

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Natural history and therapy of metastatic renal cell carcinoma

Bukowski

1997

Cancer

299

155

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The use of rIL-2 with or without IFN-alpha may represent the most useful therapeutic approach currently available for patients with good performance status. In patients with borderline performance status or severe comorbid disease, therapeutic approaches depend on patient factors and outcome expectation and may involve cytokine therapy. However, regardless of performance status, palliative measures and/or observation are important choices, because the majority of patients with metastatic RCC are incurable.

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Immunotherapy for advanced renal cell cancer

Coppin¹,

Porzsolt²,

Kumpf³

et al. 2000

The Cochrane Database of Systematic Reviews

187

175

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Phase II Study of Interferon-gamma Versus Interleukin-2 and Interferon-alpha 2b in Metastatic Renal Cell Carcinoma

Abstract: Combination therapy showed an objective response rate of 23% (p = 0.01). Although survival was not a primary aim of the study, there was a tendency toward no significant difference in survival when evaluating these relatively small groups (p = 0.49).

Cited by 26 publications

References 17 publications

Interleukin-2 in the treatment of unresectable or metastatic renal cell cancer: a systematic review and practice guideline

Interleukin-2 in the treatment of unresectable or metastatic renal cell cancer: a systematic review and practice guideline

Natural history and therapy of metastatic renal cell carcinoma

Immunotherapy for advanced renal cell cancer

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