Phase II study of subcutaneous interleukin-2 in unselected patients with advanced renal cell cancer on an outpatient basis.

Sleijfer, Dirk; Janssen, Raj; Buter, Jan; Vries, Elisabeth G.E. de; Willemse, Phb; Mulder, Nanno

doi:10.1200/jco.1992.10.7.1119

Cited by 155 publications

(50 citation statements)

References 15 publications

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“…While renal-cell carcinoma responds poorly to single-agent chemotherapy or hormonal therapy, immunotherapies with subcutaneous (s.c.) recombinant interleukin-2 (IL-2) alone or in combination with s.c. recombinant interferon-a (INF-a) yielded significant therapeutic efficacy in renal-cell carcinoma (Atzpodien et al, 1990(Atzpodien et al, , 2001(Atzpodien et al, , 2002Sleijfer et al, 1992).…”

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confidence: 99%

Metastatic renal carcinoma comprehensive prognostic system

Atzpodien

Royston

Wandert³

et al. 2003

Br J Cancer

226

145

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The purpose of the study was to identify a comprehensive prognostic system of pretreatment clinical parameters in 425 patients (pts) with metastatic renal-cell carcinoma treated with different subcutaneous (s.c.) recombinant cytokine-based home therapies in consecutive trials. Treatment consisted of (A) s.c. interferon-a2a (INF-a), s.c. interleukin-2 (IL-2) (n ¼ 102 pts), (B) s.c. IFN-a2a, s.c. IL-2, and i.v. 5-fluorouracil (5-FU) (n ¼ 235 pts) or (C) s.c. IFN-a2a, s.c. IL-2, and i.v. 5-FU combined with p.o. 13-cis-retinoic acid (13cRA) (n ¼ 88 pts). Kaplan -Meier survival analysis, log-rank statistics, and Cox regression analysis were employed to identify risk factors and to create a multiple risk factor model. The following pretreatment risk factors were identified by univariate analysis: (1) three and more metastatic sites, (2) presence of liver, lymph node or bone metastases, (3) neutrophil count X6500 cells ml À1 , (4) serum lactate dehydrogenase level (LDH) X220 U l À1 , and (5) serum C-reactive protein level (CRP) X11 mg l À1 . Cox regression analysis with forward stepwise variable selection identified neutrophil count as the major prognostic factor (hazard ratio ¼ 1.9, Po0.001), while serum levels of LDH and CRP, time between diagnosis of tumour and onset of metastatic disease, number of metastatic sites, and bone metastases were significant but somewhat less important prognostic variables within the multiple risk factor model (hazard ratio p1.5). Patients were assigned to one of the three risk groups according to cumulative risk defined as the sum of simplified risk s.c.ores for six pretreatment variables. Low-, intermediate-, and high-risk patients achieved a median overall survival of 32+ months (95% CI 24, 43; 5-year survival of 27%), 18+ months (95% CI 15, 20; 5-year survival of 11%), and 8+ months (95% CI 6, 10; 5-year survival of 5%), respectively. These prognostic categories are helpful both in individual patient care and in the assessment of patients entering prospective clinical trials.

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confidence: 99%

Metastatic renal carcinoma comprehensive prognostic system

Atzpodien

Royston

Wandert³

et al. 2003

Br J Cancer

226

145

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“…IL-2 alone (Palmer et al, 1993), but a prospective randomised trial is necessary to confirm this finding. In addition, the benefit of this combination of IL-2 and IFN-a compared with the use of alternative schedules of subcutaneous IL-2 alone needs to be investigated further (Stein et al, 1991;Sleijfer et al, 1992).…”

Section: Discussionmentioning

confidence: 99%

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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“…Subcutaneous cohorts In study SC1 (Sleijfer et al, 1992;Buter et al, 1993), s.c. injections were given for a total of 12 weeks, in three 4-week or two 6-week treatment cycles, separated by 2-or 3-week rest periods, respectively ( Figure 1A). Patients received 90 MIU (theoretically equivalent to 50 MIU m À2 week À1 ) during week 1 of each cycle (18 MIU day À1 on days 1 -5) and 72 MIU (theoretically equivalent to 40 MIU m À2 week À1 ) during weeks 2 -4 or 2 -6 of each cycle (9 MIU day À1 on days 1 and 2 and 18 MIU day À1 on days 3 -5).…”

Section: Treatmentsmentioning

confidence: 99%

“…Administration by c.i.v. was more frequently associated with adverse 17 (17) 68 (30) 85 (26) s.c. ¼ subcutaneous -Study SC1 (Protocol NL-MP-100 [Sleijfer et al, 1992;Buter et al, 1993]) and Study SC2 (Protocol EC -MP -101 [Tourani et al, 1996] et al, 1991;Geertsen et al, 1992;Negrier et al, 1992]) and Study CV2 (Protocol EC-MP-001 [Gore et al, 1994]). ECOG ¼ Eastern Cooperative Oncology Group.…”

Section: Safetymentioning

confidence: 99%

Safety and efficacy of subcutaneous and continuous intravenous infusion rIL-2 in patients with metastatic renal cell carcinoma

et al. 2004

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Phase II study of subcutaneous interleukin-2 in unselected patients with advanced renal cell cancer on an outpatient basis.

Abstract: Subcutaneous IL-2 is clinically active, has an acceptable toxicity, and can be given to patients with concomitant disease.

Cited by 155 publications

References 15 publications

Metastatic renal carcinoma comprehensive prognostic system

Metastatic renal carcinoma comprehensive prognostic system

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

Safety and efficacy of subcutaneous and continuous intravenous infusion rIL-2 in patients with metastatic renal cell carcinoma

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