Randomized phase II trial of high-dose interleukin-2 either alone or in combination with interferon alfa-2b in advanced renal cell carcinoma.

Atkins, Michael B.; Sparano, Joseph A.; Fisher, Richard I.; Weiss, Geoffrey R.; Margolin, Kim; Fink, Katharina; Rubinstein, Larry; Louie, Arthur C.; Mier, James W.; Gucalp, Rasim

doi:10.1200/jco.1993.11.4.661

Cited by 186 publications

(70 citation statements)

References 37 publications

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“…However, when patients with metastatic renal cell carcinoma were treated with the same combination of cytokines, the objective response rate obtained was 11-38% (Rosenberg et al, 1989b;Atkins et al, 1991); thus the addition of INF-a to the treatment of renal cell carcinoma with IL-2 did not appear to increase the response. It was argued that response rate might be related to the dose of cytokines given (Rosenberg et al, 1989b), although increasing cytokine doses resulted in higher toxicity (Rosenberg et al, 1989b;Atkins et al, 1991).…”

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confidence: 93%

Subcutaneous low-dose recombinant interleukin 2 and alpha-interferon in patients with metastatic renal cell carcinoma

Ravaud

Négrier²,

Cany³

et al. 1994

Br J Cancer

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A double-institution phase II study was performed in patients with metastatic renal cell carcinoma treated subcutaneously (s.c.) with interleukin 2 (IL-2) and alpha-interferon (INF-alpha). Thirty-eight patients were treated over a course of 7 weeks. Initially (day 1 + 2) patients received s.c. IL-2 at 18 x 10(6) IU m-2. During the following 6 weeks, patients received s.c. IL-2 at 3.6 x 10(6) IU m-2 for 5 days per week and s.c. INF-alpha at 5 x 10(6) for 3 days per week. Thirty-eight patients were evaluated for response. An objective response was seen in seven patients (18.4 +/- 12.3%), with one complete response and six partial responses. Median duration of response was 6.7 months. Toxicity could be evaluated in 38 patients and was limited. Mild to moderate toxicity included fever (97%), fatigue or malaise (76%), nausea or vomiting (50%), anorexia (32%), hypotension (26%), neurological disturbances (26%) and hypercreatininaemia (39%). In addition, four grade IV haematological toxicities were noted. No cardiac side-effects were seen. IL-2 and INF-alpha given by this schedule can be safely administered in an outpatient setting. The objective response rate was similar to our previous treatments with high-dose IL-2 given as a continuous infusion.

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confidence: 93%

Subcutaneous low-dose recombinant interleukin 2 and alpha-interferon in patients with metastatic renal cell carcinoma

Ravaud

Négrier²,

Cany³

et al. 1994

Br J Cancer

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“…Atkins and others, 39 in their randomized phase 2 trial of high-dose IL-2 with and without interferon-α, found no difference in response in either group. However, toxicity was higher with the addition of interferon-α.…”

Section: Interferon and Il-2 Combination Regimensmentioning

confidence: 94%

“…Results of a review 39 of more than 1400 patients receiving interferon-α and IL-2 indicated an overall RR of 20% for the combination, and found that 3%-5% of patients had CRs.…”

Section: Interferon and Il-2 Combination Regimensmentioning

confidence: 99%

Current status of cytokine therapy in management of patients with metastatic renal cell carcinoma

Kapoor

Hotte

2012

CUAJ

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Studies examining the efficacy of immunotherapy have used a variety of end points such as response rate (RR), complete response (CR) or partial response (PR); rate of progression; and progression-free and median survival. However, these studies used different definitions of these end points and none was blinded.5 Further, RR has been reported to be an unreliable surrogate of survival. 5A meta-analysis 7 of 1042 patients found that the overall proportion of responses (CR and PR) to interferon-α was 12%. CRs were quite rare. Favourable characteristics of responders included patients with prior nephrectomy and patients with lung metastases. In this particular patient population, the proportion of objective responses was as high as 44%. 7 The average time from the start of treatment to an objective response was about 3-4 months. Metastases of the central nervous system tended not to respond to interferon, and soft-tissue disease tended to respond more readily than bony metastases. Results of a review of more than 1500 patients 8 suggest that the disease RR is between 12% and 15% for patients receiving interferon-α. CRs occurred in 2%-5% patients, usually in those with pulmonary metastases. The recently published Cochrane collaboration review 5 estimated a gain of 3.8 months and a 1-year risk of mortality reduction by 44% for patients randomized to interferon-α2a, compared with patients randomized to control arms. Toxicity with interferon-α includes fever, malaise, flulike symptoms and night sweats, and is markedly less than that with interleukin-2 (IL-2). S28 REVIEW AbstractCytokine therapy with interferon-α and interleukin-2 has arguably been the standard treatment for patients with metastatic renal cell carcinoma for more than 20 years. In this paper, the current evidence for the use of cytokine therapy in this patient population is discussed, including the significant toxicity associated with these agents. A low overall response rate and a marginal survival advantage are observed with interferon-α and interleukin-2; however, these therapies have significant toxicity and impair quality of life. Unlike the current tyrosine-kinase inhibitors, complete tumour responses may be seen with interleukin-2, but again this therapy has significant morbidity and mortality. Newer anti-angiogenesis agents may be combined with current standard cytokine therapy for patients with metastatic renal cell carcinoma.

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“…A sxnergistic response was confirmed in mice (Cameron et al 1988) and this led to the development of combination regimens that were associated wvith an ox erall response rate of up to 29%7 (Atzpodien et al 1990. 1991: Palmer et al 1993: Canobbio et al 1996b: Gause et al 1996 Savage et al 1996) wxith a median survival of 8-12 months (Facendola et al 1995: Canobbio et al 1996a Correspondence to: GC Jayson hN-potension and creatinine elexvation (Atkins et al 1993: Gause et al. 1996. factors that led to the premature discontinuation of therapy in 14% of patients (Facendola et al 1995).…”

mentioning

confidence: 99%

“…hN-potension and creatinine elexvation (Atkins et al 1993: Gause et al 1996. factors that led to the premature discontinuation of therapy in 14% of patients (Facendola et al 1995).…”

mentioning

confidence: 99%

A randomized phase II trial of interleukin 2 and interleukin 2-interferon alpha in advanced renal cancer

Jayson

Middleton²,

Lee³

et al. 1998

Br J Cancer

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Summary A randomized phase 11 trial was performed to compare the efficacy and toxicity of interleukin 2 (IL-2) with an IL-2 and interferon alpha (IFN-a) regimen for the treatment of metastatic renal carcinoma. Sixty patients with recurrent renal cell carcinoma (RCC) who had previously undergone a nephrectomy were randomized to receive three cycles of IL-2 or IL-2 with IFN-a,. Eighteen al. 1996).Experimental data suggested that a combination of IL-2 and IFN-a might offer superior efficacy. Interferon enhances the cell membrane expression of major histocompatibility complex (MHC) antigens to %%-hich IL-2-activated T cells can respond (Guadagni et al. 1989). A sxnergistic response was confirmed in mice (Cameron et al. 1988) and this led to the development of combination regimens that were associated wvith an ox erall response rate of up to 29%7 (Atzpodien et al. 1990. 1991: Palmer et al. 1993: Canobbio et al. 1996b: Gause et al. 1996 Savage et al. 1996) wxith a median survival of 8-12 months (Facendola et al. 1995: Canobbio et al. 1996a Correspondence to: GC Jayson hN-potension and creatinine elexvation (Atkins et al. 1993: Gause et al. 1996. factors that led to the premature discontinuation of therapy in 14% of patients (Facendola et al. 1995).We haxe performed a phase I trial to determine the maximum

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Randomized phase II trial of high-dose interleukin-2 either alone or in combination with interferon alfa-2b in advanced renal cell carcinoma.

Cited by 186 publications

References 37 publications

Subcutaneous low-dose recombinant interleukin 2 and alpha-interferon in patients with metastatic renal cell carcinoma

Subcutaneous low-dose recombinant interleukin 2 and alpha-interferon in patients with metastatic renal cell carcinoma

Current status of cytokine therapy in management of patients with metastatic renal cell carcinoma

A randomized phase II trial of interleukin 2 and interleukin 2-interferon alpha in advanced renal cancer

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