Interleukin-2, Interferon-α and Interleukin-2 plus Interferon-α in Renal Cell Carcinoma. A Randomized Phase Ii Trial

1998 ◽  
Vol 84 (5) ◽  
pp. 534-539 ◽  
Author(s):  
Francesco Boccardo ◽  
Alessandra Rubagotti ◽  
Luciano Canobbio ◽  
Enzo Galligioni ◽  
Roberto Sorio ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Objective Response ◽  
Interleukin 2 ◽  
Drug Dose ◽  
Response To Treatment ◽  
Interferon Α ◽  
Daily Dose ◽  
To Receive

Background The purpose of the present study was to investigate the therapeutic effectiveness of interleukin-2 (IL-2) and interferon (IFN), either alone or in combination, in comparable groups of patients affected by advanced renal cell carcinoma (RCC). Patients and methods In order to limit selection biases, treatment was allocated on a random basis. Patients randomized to IL-2 alone were scheduled to receive eight rIL-2 24-hour i.v. infusion cycles, days 1 to 4, at a daily dose of 18 x 106 IU/m2 for a total of 25 weeks. Patients randomized to IFN alone were scheduled to receive rIFN-α at a daily dose of 6 x 106 IU/m2, days 1, 3 and 5, every week for a total of 52 weeks. Patients randomized to the combination of IFN and IL-2 were given the same drugs at the same daily doses for a total of 24 weeks. Drug dose was modified according to toxicity. Results Twenty-three percent (95% CI: ± 17.5) of patients treated with IL-2 alone showed an objective response to treatment (9% CR). The corresponding figures in patients treated with IFN alone or IFN plus IL-2 were 9% (95% CI: ± 11.9) and 9% (95% CI: ± 11.9), respectively. Complete responses were observed only in patients treated with IL-2. The median duration of response in the IL-2 arm was 18 months (range, 9.5-24). The duration of the two responses achieved by IFN alone was seven and nine, months, respectively. The corresponding figures in the two patients responding to the combination of IFN with IL-2 were 19 and 27 months, respectively. Total IL-2 dose appeared to be a major predictor of response. Only a minority of patients experienced grade 3-4 toxicity, the incidence being higher in those treated with IL-2 or IL-2 plus IFN. Conclusions Neither IFN nor IL-2 or the combination of the two appear to be very active in patients with advanced RCC, even when trial entry was restricted to patients with relatively indolent disease. This stresses the need for the development of new approaches.

Renal cell carcinoma: treatment with recombinant interleukin-2 plus beta-interferon.

1990 ◽  
Vol 8 (3) ◽  
pp. 460-467 ◽  
Author(s):  
R L Krigel ◽  
K A Padavic-Shaller ◽  
A R Rudolph ◽  
M Konrad ◽  
E C Bradley ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Local Recurrence ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Nk Cell ◽  
Objective Response ◽  
Interleukin 2 ◽  
Cell Activity ◽  
Nk Cell Activity ◽  
Beta Interferon

Preclinical data have demonstrated synergy between interleukin-2 (IL-2) and beta-interferon (IFN-beta) in stimulating natural-killer (NK) cell activity and in increasing expression of IL-2 receptors. Based on results of a phase I trial, a combination of IL-2 and IFN-beta was administered three times weekly by intravenous (IV) bolus injection with 5 x 10(6) Cetus U/m2 of IL-2 and 6 x 10(6) U/m2 of IFN-beta to 24 patients with advanced renal cell carcinoma (RCC). Of 22 assessable patients there were six (27%) objective responses including one complete remission (CR) and five partial responses (PRs). There were three minor responses (MRs), 11 stable disease (SD), and two progressive disease (PD). Two of the objective responses have continued for almost 2 years. Response sites include lymph nodes, lungs, and bone. Toxicities requiring dose reduction include arthralgia, weight loss, fatigue, decreased performance status, depression, and hypotension. Five of 10 patients who had a prior nephrectomy without local recurrence achieved an objective response as compared with only one of 12 without a prior nephrectomy or with a local recurrence (P = .04). Mean peak lymphokine-activated killer (LAK) cell activity of the objective responders was 88 lytic units (LU) as compared with 4 LU in the nonresponders (P = .01). Mean peak NK cell activity was 288 LU in the objective responders as compared with 100 LU in the nonresponders (P = .10).(ABSTRACT TRUNCATED AT 250 WORDS)

Results of treatment of 255 patients with metastatic renal cell carcinoma who received high-dose recombinant interleukin-2 therapy.

1995 ◽  
Vol 13 (3) ◽  
pp. 688-696 ◽  
Author(s):  
G Fyfe ◽  
R I Fisher ◽  
S A Rosenberg ◽  
M Sznol ◽  
D R Parkinson ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Metastatic Renal Cell Carcinoma ◽  
Renal Cell ◽  
Objective Response ◽  
Eastern Cooperative Oncology Group ◽  
Interleukin 2 ◽  
High Dose ◽  
Primary Tumors ◽  
Median Response

PURPOSE To determine the efficacy and toxicity of a high-dose interleukin-2 (IL-2) regimen in patients with metastatic renal cell carcinoma. PATIENTS AND METHODS Two hundred fifty-five assessable patients were entered onto seven phase II clinical trials. Proleukin (aldesleukin; Chiron Corp, Emeryville, CA) 600,000 or 720,000 IU/kg was administered by 15-minute intravenous (i.v.) infusion every 8 hours for up to 14 consecutive doses over 5 days as clinically tolerated with maximum support, including pressors. A second identical cycle of treatment was scheduled following 5 to 9 days of rest, and courses could be repeated every 6 to 12 weeks in stable or responding patients. RESULTS The overall objective response rate was 14% (90% confidence interval [CI], 10% to 19%), with 12 (5%) complete responses (CRs) and 24 (9%) partial responses (PRs). Responses occurred in all sites of disease, including bone, intact primary tumors, and visceral metastases, and in patients with large tumor burdens or bulky individual lesions. The median response duration for patients who achieved a CR has not been reached, but was 19.0 months for those who achieved a PR. Baseline Eastern Cooperative Oncology Group (ECOG) performance status (PS) was the only predictive prognostic factor for response to IL-2. While treatment was associated with severe acute toxicities, these generally reversed rapidly after therapy was completed. However, 4% of patients died of adverse events judged to be possibly or probably treatment-related. CONCLUSION High-dose IL-2 appears to benefit some patients with metastatic renal cell carcinoma by producing durable CRs or PRs. Despite severe acute treatment-associated toxicities, IL-2 should be considered for initial therapy of patients with appropriately selected metastatic renal cell carcinoma.

Treatment of metastatic papillary renal cell carcinoma with immunochemotherapy with interleukin-2, interferon-alpha and 5- fluorouracil

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 15644-15644 ◽  
Author(s):  
E. Herrmann ◽  
O. A. Brinkmann ◽  
M. E. Bode ◽  
S. Bierer ◽  
T. Köpke ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Interferon Alpha ◽  
Renal Cell ◽  
Objective Response ◽  
Interleukin 2 ◽  
Papillary Renal Cell Carcinoma ◽  
First Line ◽  
Histologic Subtype ◽  
First Line Therapy

15644 Background: Combined immunochemotherapy with interleukin-2 (IL-2), interferon-alpha (IFN-a) and 5-fluorouracil (5-FU) is an established first-line therapy for metastatic renal cell carcinoma (RCC). However, data on histologic parameters predictive of clinical benefit are rare. Methods: Treatment courses of 164 patients consisted of IFN-a at 9 x 106 IU on day 1 of weeks 1 and 4 and days 1, 3, 5 of weeks 2 and 3; and at 18 x 106 IU on days 1, 3, 5 of weeks 5–8. Interleukin-2 was administrated at 18 x 106 IU twice daily on days 3–5 of weeks 1 and 4; and at 9 x 106 IU on days 1, 3, 5 of weeks 2 and 3. Additionally, patients received 5-FU at 750 mg m-2 on day 1 of weeks 5–8. In 153 patients, radical nephrectomy had revealed 22 cases of papillary RCC (pRCC, 13.4%) and 131 cases of clear cell RCC (ccRCC, 79.9%). In the remaining 11 (6.7%) their disease was inoperable. The overall response rates were evaluated according to WHO criteria. Results: For ccRCC and inoperable disease, responses of 34.4% and 27.3% after one cycle and 28.8% and 16.7% after two cycles, respectively, were noted. In contrast, no patient with pRCC showed any response after two cycles of combined immunochemotherapy. Conclusions: No objective response was seen in patients with pRCC. Hence, immunotherapeutic agents must be questioned in this histologic subtype. No significant financial relationships to disclose.

A phase 2 study of cabozantinib as first-line treatment in collecting ducts renal cell carcinoma: The BONSAI trial.

2018 ◽  
Vol 36 (6_suppl) ◽  
pp. TPS709-TPS709
Author(s):  
Giuseppe Procopio ◽  
Raffaele Ratta ◽  
Giovanni Fucà ◽  
Paolo Grassi ◽  
Luca Porcu ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Objective Response ◽  
Locally Advanced ◽  
Progression Free Survival ◽  
Primary Objective ◽  
Response To Treatment ◽  
Second Stage ◽  
Collecting Ducts

TPS709 Background: Collecting ducts carcinoma (CDC) is a rare and aggressive form of renal cell carcinoma, characterized by extremely poor prognosis and resistance to agents effective in other forms of RCC. We hypothesized that cabozantinib, an inhibitor of multiple kinases including VEGFR 2, MET and AXL, may be superior in terms of efficacy to other angiogenesis inhibitors in the treatment of CDC due to its high-spectrum of activity against multiple and non-redundant oncogenic pathways. Methods: The BONSAI study is a prospective, single-centre, single-arm phase II trial evaluating cabozantinib in patients with untreated locally advanced or metastatic CDC. Cabozantinib will be administered at the dose of 60 mg orally once daily until the evidence of disease progression (PD) evaluated by RECIST 1.1 or unacceptable toxicity. Primary objective is the evaluation of objective response rate (ORR). Secondary endpoints are progression-free survival (PFS), overall survival (OS) and safety profile of cabozantinib. Exploratory objectives include the evaluation of genetic and immunological landscape of CDC and its correlation with response to treatment. Overall, 23 patients will be enrolled into the study based on a Simon’s two-stage optimal design. In order to reject an ORR equal to 15% with a one-sided alpha error of 10% and to detect an ORR equal to 35% with a power of 80%, 9 patients will be enrolled in the first stage. If at least 2 responses will be observed in the first stage, 14 additional patients will be included in the second stage. If at least 6 responses will be observed at the second stage the activity of cabozantinib will be proved. First patient enrollment is scheduled in November 2017.

Pilot Trial of Infusional 5-Fluorouracil, Interleukin-2, and Subcutaneous Interferon-α for Advanced Renal Cell Carcinoma

1999 ◽  
Vol 22 (2) ◽  
pp. 156-161 ◽  
Author(s):  
Laurence Elias ◽  
Mitchell Binder ◽  
Aroop Mangalik ◽  
Douglas Clark ◽  
Betsy Morrison ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Pilot Trial ◽  
Interleukin 2 ◽  
Advanced Renal Cell Carcinoma ◽  
Interferon Α
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