Concomitant administration of recombinant human interleukin-2 and recombinant interferon alfa-2A: an active outpatient regimen in metastatic renal cell carcinoma.

1992 ◽  
Vol 10 (3) ◽  
pp. 414-421 ◽  
Author(s):  
R A Figlin ◽  
A Belldegrun ◽  
N Moldawer ◽  
J Zeffren ◽  
J deKernion
Keyword(s):  
Renal Cell Carcinoma ◽  
Complete Remission ◽  
Cell Carcinoma ◽  
Metastatic Renal Cell Carcinoma ◽  
Renal Cell ◽  
Interleukin 2 ◽  
Interferon Alfa ◽  
Clinical Activity ◽  
Recombinant Interferon ◽  
Ifn Alpha

PURPOSE A phase II trial of interleukin-2 (IL-2) and interferon alfa (IFN-alpha) in metastatic renal cell carcinoma (RCCa) was conducted. A lower dosage of IL-2 was given via continuous intravenous (IV) infusion, a route with documented tumor activity associated with less toxicity, with the purpose of improving the therapeutic index of this treatment in an outpatient setting. PATIENTS AND METHODS Thirty patients with metastatic RCCa were treated with the combination of IL-2 and IFN-alpha-2A. IL-2 was administered on days 1 through 4 of each treatment week, as a continuous IV infusion at a dose of 2 x 10(6) U/m2/d. IFN-alpha-2A was administered intramuscularly or subcutaneously on days 1 and 4 of each treatment week, at a dose of 6 x 10(6) U/m2/d. One treatment course included 4 weeks of treatment followed by a 2-week rest. Patients received therapy as outpatients except for the first 4 days of treatment, cycle 1 only. All patients were assessable for toxicity and response assessment. A total of 105 courses of therapy were administered, 51% at full dose. RESULTS Sixteen patients experienced toxicities resulting in dosage modification. The major treatment-limiting toxicities were gastrointestinal, neurologic, and fatigue. Nine patients (30%) had partial remissions (PRs) with a median duration of responses of 12+ months. The median time to response was 11 weeks. Two partial responders whose sites of metastatic disease were renal fossa and mediastinal lymph nodes (LN), respectively, were found to have achieved a pathologic complete remission (pCR) after surgery. A third patient with a pCR of axillary LN was rendered into a surgical complete remission (sCR) with salvage nephrectomy. Median survival of patients obtaining a PR has not been reached with a median follow-up time of 19+ months. CONCLUSION IL-2 and IFN-alpha-2A is well tolerated in the outpatient treatment setting and demonstrates significant clinical activity against RCCa.

Multiinstitutional home-therapy trial of recombinant human interleukin-2 and interferon alfa-2 in progressive metastatic renal cell carcinoma.

1995 ◽  
Vol 13 (2) ◽  
pp. 497-501 ◽  
Author(s):  
J Atzpodien ◽  
E Lopez Hänninen ◽  
H Kirchner ◽  
H Bodenstein ◽  
M Pfreundschuh ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Metastatic Renal Cell Carcinoma ◽  
Renal Cell ◽  
Interleukin 2 ◽  
Interferon Alfa ◽  
World Health ◽  
Home Therapy ◽  
Who Grade ◽  
Recombinant Interferon

PURPOSE In a phase II multiinstitutional outpatient trial, patients with progressive metastatic renal cell carcinoma were treated with a combination of subcutaneous (SC) recombinant interleukin-2 (rIL-2) and recombinant interferon alfa-2 (rIFN alpha 2). PATIENTS AND METHODS One hundred fifty-two patients with metastatic renal cell carcinoma were treated. Treatment courses consisted of SC rIL-2 at 20 x 10(6) IU/m2 three times per week in weeks 1 and 4, and at 5 x 10(6) IU/m2 three times per week in weeks 2, 3, 5, and 6. Additionally, patients received SC rIFN alpha 2 6 x 10(6) U/m2 once per week in weeks 1 and 4, and three times per week in weeks 2, 3, 5, and 6. RESULTS There were nine (6%) complete responses (CRs) and 29 (19%) partial responses (PRs), for an overall response rate of 25% (95% confidence interval, 19% to 32%). The median duration of responses for CRs and PRs was 16+ and 9 months, respectively. Additionally, 55 patients (36%) had stable disease (SD). Fifty-nine patients (39%) had continued disease progression (PD) despite treatment, or went off study after less than 4 weeks of therapy. The majority of patients treated experienced fever, chills, malaise, nausea, vomiting, and anorexia, side effects that were mostly limited to World Health Organization (WHO) grade 1 and 2. However, one patient developed grade 4 CNS toxicity with extended somnolence. On cessation of therapy, the neurologic symptoms in this patient were fully reversible, with no neurologic deficiency. CONCLUSION In summary, this multiinstitutional home-therapy setting of SC rIL-2 and SC rIFN alpha 2 in patients with progressive metastatic renal cell carcinoma demonstrated drastically reduced systemic toxicity, while it confirmed the therapeutic efficacy of the low-dose SC immunotherapy combination schedule.

A phase IA trial of sequential administration recombinant DNA-produced interferons: combination recombinant interferon gamma and recombinant interferon alfa in patients with metastatic renal cell carcinoma.

1990 ◽  
Vol 8 (10) ◽  
pp. 1637-1649 ◽  
Author(s):  
M S Ernstoff ◽  
S Nair ◽  
R R Bahnson ◽  
L M Miketic ◽  
B Banner ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Complete Remission ◽  
Cell Carcinoma ◽  
Dose Level ◽  
Interferon Gamma ◽  
Metastatic Renal Cell Carcinoma ◽  
Renal Cell ◽  
Interferon Alfa ◽  
Recombinant Interferon ◽  
Clinical Responses

This study investigated the effects of sequentially administered recombinant interferon gamma (rIFN gamma) and recombinant interferon alfa (rIFN alpha) in 36 patients with metastatic renal cell carcinoma (RCC). rIFN alpha was subcutaneously administered daily for 70 days at dosages that varied (2.5, 5, 10, and 20 x 10(6) U/m2) across four cohorts of patients. Within each cohort of patients receiving a given dose of rIFN alpha, three subsets of patients received either 30, 300, or 1,000 micrograms/m2 rIFN gamma. rIFN gamma was administered intravenously for 5 days every third week, 6 hours prior to administration of rIFN alpha. Dose-limiting toxicity (DLT) included constitutional symptoms, leukopenia, nephrotic syndrome with acute renal failure, hypotension associated with death, and congestive heart failure. DLT was related more often to the rIFN alpha dose level than to rIFN gamma dose level. Maximum-tolerated dose (MTD) was 10 x 10(6) U/m2 rIFN alpha and 1,000 micrograms/m2 rIFN gamma. Six patients failed to complete a minimum of 21 days of therapy due to toxicity or rapid progression of disease. Clinical responses were seen in eight of 30 assessable patients. Two patients experienced complete remission and have remained in complete remission 20+ and 22+ months. An additional six patients have shown partial responses for 4 to 18+ months. One patient in partial remission continues to show slow regression of pulmonary and liver lesions off therapy with rIFNs. Clinical responses have remained durable for patients with complete remissions and patients with partial remissions. The results of this study suggest that toxicities associated with combination rIFN therapy can be reduced by administering these agents sequentially as opposed to simultaneously.

Outpatient treatment with subcutaneous interleukin-2 and interferon alfa administration in combination with fluorouracil in patients with metastatic renal cell carcinoma: results of a sequential nonrandomized phase II study. Subcutaneous Administration Propeukin Program Cooperative Group.

1998 ◽  
Vol 16 (7) ◽  
pp. 2505-2513 ◽  
Author(s):  
J M Tourani ◽  
C Pfister ◽  
J F Berdah ◽  
A Benhammouda ◽  
P Salze ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Metastatic Renal Cell Carcinoma ◽  
Renal Cell ◽  
Survival Rates ◽  
Interleukin 2 ◽  
Subcutaneous Administration ◽  
Severe Toxicity ◽  
Prognosis Factors ◽  
Ifn Alpha

PURPOSE We report the results of the Subcutaneous Administration Propeukin Program (SCAPP) II trial of an outpatient treatment in renal cell carcinoma using interleukin-2 (IL-2) and interferon alfa-2a (IFN-alpha) administered subcutaneously in combination with fluorouracil (5-FU). The objective of this multicenter trial was to confirm that the combination of IL-2, IFN-alpha, and 5-FU leads to a response rate greater than 20%. PATIENTS AND METHODS Patients with metastatic renal cell carcinoma were included in this study. During the induction phase of the treatment, which lasted 10 weeks, IL-2 and IFN-alpha were administered subcutaneously three times a week for 8 weeks at doses of 18 MIU and 9 MIU, respectively. During these 8 weeks, every Monday, 5-FU was administered at a dose of 750 mg by intravenous infusion over 30 minutes. After evaluation, responding patients or patients with stable disease (SD) were given maintenance treatment, until disease progression (PD) or the appearance of unacceptable toxicity. Each maintenance cycle consisted of a 2-week treatment followed by a three-week rest period. During treatment, IL-2 and IFN-alpha were administered subcutaneously three times a week at doses of 18 MIU and 9 MIU, respectively. Every Monday, 5-FU was administered at a dose of 750 mg by intravenous infusion over 30 minutes. RESULTS This trial was closed when the sixth sequential analysis showed the lack of benefit from this combination. At the end of the induction period, of 62 patients, 12 (19%; 95% confidence interval [CI], 10% to 31%) reached an objective response, including one complete response (CR), 16 presented with SD, and 27 showed PD. Twenty-seven patients (43%) developed severe toxicity that required reduction of the planned doses (13 patients), delayed treatment (eight patients), or treatment termination (six patients). Seventeen patients were given maintenance treatment. One- and 2-year survival rates were estimated at 55% and 33%, respectively. The 2-year survival rate was 15% in 11 patients who presented with three poor-prognosis factors and 41% in 51 patients who initially presented with no, one, or two poor-prognosis factors (P = .04). CONCLUSION As in other recently published studies that used 5-FU, IL-2, and IFN-alpha, the multicenter SCAPP II trial in patients with metastatic renal cell carcinoma generated severe toxicity. This sequential trial failed to confirm the favorable results previously obtained by Atzpodien and Sella with this combination of three drugs. Its efficacy, assessed on the response and survival rates, is near to the results observed in programs that used IL-2 alone given subcutaneously.

Subcutaneous interleukin-2, interferon alfa-2a, and continuous infusion of fluorouracil in metastatic renal cell carcinoma: a multicenter phase II trial. Groupe Français d'Immunothérapie.

1998 ◽  
Vol 16 (8) ◽  
pp. 2728-2732 ◽  
Author(s):  
A Ravaud ◽  
B Audhuy ◽  
F Gomez ◽  
B Escudier ◽  
T Lesimple ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Continuous Infusion ◽  
Phase Ii ◽  
Metastatic Renal Cell Carcinoma ◽  
Renal Cell ◽  
Renal Carcinoma ◽  
Phase Ii Trial ◽  
Interleukin 2 ◽  
Interferon Alfa

PURPOSE A phase II trial was designed to determine the efficacy and the tolerance of interleukin-2 (IL-2), interferon alfa-2a (IFNalpha), and fluorouracil (5-FU) in patients with metastatic renal cell carcinoma. PATIENTS AND METHODS One hundred eleven patients were included. Patients received subcutaneous IL-2 9 x 10(6) IU daily for 6 days and IFNalpha 6 x 10(6) IU on days 1, 3, and 5 every other week for 8 weeks. 5-FU was administered through a continuous infusion at 600 mg/m2 for 5 consecutive days for 1 week every 4 weeks. RESULTS The response rate was 1.8% (95% confidence interval [CI], 0% to 4.3%) with only two partial responses (PRs). Toxicity was moderate with 3.6% grade 4 events and two deaths related to treatment. CONCLUSION This regimen of IL-2, IFNalpha, and 5-FU in patients with metastatic renal cell carcinoma was ineffective. The results raise the question of the dose and schedule of subcutaneous cytokines that must be used in metastatic renal carcinoma.

A phase II trial of interleukin-2 and interferon alfa-2a in patients with advanced renal cell carcinoma.

1992 ◽  
Vol 10 (7) ◽  
pp. 1124-1130 ◽  
Author(s):  
D H Ilson ◽  
R J Motzer ◽  
R L Kradin ◽  
N J Vogelzang ◽  
D F Bajorin ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Prognostic Factors ◽  
Cell Carcinoma ◽  
Phase Ii ◽  
Renal Cell ◽  
Phase Ii Trial ◽  
Interleukin 2 ◽  
Complete Response ◽  
Interferon Alfa ◽  
Ifn Alpha

PURPOSE A phase II trial that used a regimen of interleukin-2 (IL-2) and interferon alfa-2a (IFN-alpha) was undertaken to evaluate the efficacy of this combination in the treatment of metastatic renal cell carcinoma. PATIENTS AND METHODS Thirty-four assessable patients were treated with one to two induction cycles of IL-2 administered by continuous intravenous (IV) infusion at a dose of 3 x 10(6) U/m2/d [corrected] for 4 days per week plus IFN-alpha administered by subcutaneous injection at a dose of 5 x 10(6) U/m2/d [corrected] for 4 days per week for 3 consecutive weeks. A maintenance regimen of IL-2 2 x 10(6) U/m2/d [corrected] given by continuous IV infusion for 5 days per week plus IFN-alpha subcutaneously at a dose of 6 x 10(6) U/m2/d [corrected] that was given 3 days per week for 3 weeks was administered for one to five cycles. Twenty-eight patients (82%) completed one to two induction cycles, and 14 patients (41%) received maintenance doses. RESULTS Major responses were achieved in four patients (12%), which included one complete response (CR) in a bone metastasis. Responses were observed in patients both with and without prior nephrectomy as well as in a primary tumor. Toxicity was moderately severe and included two treatment-related deaths. CONCLUSIONS In view of the minimal antitumor activity and associated toxicity, the combination of IL-2 and IFN-alpha in this trial cannot be recommended. The investigation of new cytokines and the identification of biologic prognostic factors for a response to immunologic therapy are essential.

Phase II study of interferon alfa-2a, recombinant (Roferon-A) in metastatic renal cell carcinoma.

1987 ◽  
Vol 5 (7) ◽  
pp. 1083-1089 ◽  
Author(s):  
A C Buzaid ◽  
A Robertone ◽  
C Kisala ◽  
S E Salmon
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Metastatic Renal Cell Carcinoma ◽  
Renal Cell ◽  
Locally Advanced ◽  
Interferon Alfa ◽  
Induction Phase ◽  
Optimal Dosage ◽  
Metastatic Renal Cancer ◽  
Recombinant Interferon

In an attempt to decrease toxicity without compromising efficacy, 22 patients with locally advanced or metastatic renal cell carcinoma (RCC) were treated with recombinant interferon alfa-2a (rIFN alpha 2a, Roferon-A; Hoffman-LaRoche, Nutley, NJ) intramuscularly (IM) beginning at a dose of 3 X 10(6) U/d with incremental dose escalations to the highest dose of 36 X 10(6) U/d if tolerated, for a total induction period of 10 weeks. Patients demonstrating complete (CR), partial (PR), or minor (MR) responses or stabilization were continued on a maintenance regimen of the highest tolerated dose administered three times weekly until disease progression. Doses administered during maintenance were individually determined as the maximum dose that resulted in only mild toxicity. No CRs were achieved. Partial responses were observed in 23% of the patients with a median duration of response of 8.0 months (range, 1 to 17+). The majority of interferon side effects were seen during the induction phase, which was also the period requiring the most frequent adjustments in dose. In comparison to another study using similar toxicity criteria, overall toxicity was reduced in severity, most probably due to the study design, which allowed individual tailoring of doses. The use of an initial induction phase employing rapid dose escalation followed by a well-tolerated maintenance phase appeared to be a reasonable strategy. The therapeutic results to date represent a modest advance. An optimal dosage, route, and schedule for interferon administration for metastatic renal cancer is not yet clearly established.

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