Activity of retreatment with sorafenib for metastatic renal cell carcinoma.

2011 ◽  
Vol 29 (7_suppl) ◽  
pp. 404-404 ◽  
Author(s):  
M. Nozawa ◽  
N. Matsumura ◽  
M. Yasuda ◽  
Y. Okuda ◽  
H. Uemura
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Metastatic Renal Cell Carcinoma ◽  
Clinical Benefit ◽  
Renal Cell ◽  
Objective Response ◽  
Interleukin 2 ◽  
Severe Toxicity ◽  
Sorafenib Therapy ◽  
Significant Difference

404 Background: Treatment options for metastatic renal cell carcinoma (mRCC) have increased. Complete remission is, however, rarely seen and patients are treated with multiple sequential therapies. We assessed clinical activity of sorafenib rechallenge after progressing on other therapies. Methods: Patients with mRCC who received a second course of sorafenib therapy after failure of prior sorafenib and other agents were retrospectively identified. RECIST-defined objective response rate and progression-free survival (PFS) and toxicity were analyzed. Results: Fourteen patients with mRCC who were retreated with sorafenib were identified and twelve patients were assessable for this study. 92% were male. Median age at first systemic therapy was 63 years. Prior nephrectomy was performed in 92% of patients. 42% of patients had favorable or intermediate risk, 17% poor, and the rest not available per MSKCC criteria. Eighty-three percent of patients were treated with other agents before initial sorafenib therapy, including 75% interferon-alpha (IFN-alpha), 50% interleukin-2 (IL-2), and 17% sunitinib. First sorafenib therapy began a median of 9.0 months after the diagnosis of mRCC and produced a clinical benefit (PR + SD) rate of 75% and a median PFS of 5.0 months. 67% of patients discontinued initial sorafenib for disease progression and 33% for adverse events. Interval between discontinuation of initial sorafenib and rechallenge was a median of 7.6 months. During the intervening period, 50% of patients were treated with sunitinib, 33% with everolimus, 25% with VEGFR1 vaccine, and others. Clinical benefit rate of 67% and a median PFS of 4.3 months were obtained on sorafenib rechallenge. There was no significant difference in outcome to sorafenib rechallenge based on duration between sorafenib treatments or number or type of intervening treatments. No new severe toxicity was observed during rechallenge. Conclusions: Sorafenib rechallenge has potential to achieve clinical benefits, is well-tolerated, and may be considered after multiple sequential therapies in select mRCC patients. No significant financial relationships to disclose.

Interleukin-2, interferon alpha and 5-fluorouracil immunochemotherapy with and without 13-cis-retinoic acid in patients with metastatic renal cell carcinoma: Results of a prospective randomized trial

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 14571-14571
Author(s):  
S. Bierer ◽  
M. E. Bode ◽  
O. A. Brinkmann ◽  
L. Hertle
Keyword(s):  
Renal Cell Carcinoma ◽  
Retinoic Acid ◽  
Cell Carcinoma ◽  
Interferon Alpha ◽  
Metastatic Renal Cell Carcinoma ◽  
Renal Cell ◽  
Objective Response ◽  
Interleukin 2 ◽  
Significant Difference ◽  
Group B

14571 Background: Combined immunochemotherapy with interleukin 2, interferon alpha and 5-fluorouracil in patients with metastatic renal cell carcinoma has shown objective response rates up to 30% and more. The therapeutic effect of adding 13-cis-retinoic acid still remains controversial. Methods: Between 05/2001 and 11/2003 we randomly assigned patients with metastatic renal cell carcinoma either to receive a combined immunochemotherapy of interleukin 2 (s.c.), interferon alpha (s.c.) and 5-fluorouracil (i.v.) = group A or the same regimen plus 3 × 20 mg 13-cis-retinoic acid daily (p.o.) = group B. 83 patients were eligible (41 in group A and 43 in group B). All patients had ECOG 0 or 1 and no prior systemic therapy. Objective response (OR = Complete response, CR + Partial response, PR + Stable disease, SD), time to progression (TTP) and median survival were determined. Results: Patient characteristics were well balanced between both groups. There was no significant difference in objective response between both groups (A/B: CR 2%/2%, PR 22%/5%, SD 46%/69%, p = 0.8). The responders in both groups showed no significant difference in TTP (A/B: 11.5/9.5 months, p = 0.4). Median survival was 23 months for all patients with no significant difference between the two groups (A/B: 26/22 months, p = 0.42). Slightly more therapeutic side effects (e.g. mucositis) were seen in group B. Conclusions: The addition of 13-cis-retinoic acid to a combined immunochemotherapy of interleukin 2, interferon alpha and 5-fluorouracil in patients with metastatic renal cell carcinoma does not seem to have a therapeutic benefit. No significant financial relationships to disclose.

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.

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.

A prospective, open label, multicenter, randomized phase II trial: Sequential therapy with bevacizumab, RAd001 (everolimus) and axitinib in metastatic renal cell carcinoma (mRCC) (BERAT study).

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e16097-e16097
Author(s):  
Viktor Grünwald ◽  
Lothar Bergmann ◽  
Peter J. Goebell ◽  
Arne Strauss ◽  
Johannes Meiler ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Phase Ii ◽  
Metastatic Renal Cell Carcinoma ◽  
Renal Cell ◽  
Phase Ii Trial ◽  
Objective Response ◽  
Line Treatment ◽  
Open Label ◽  
Significant Difference

e16097 Background: Inhibitors of the vascular endothelial growth factor (VEGF), its receptor (Ri) or mammalian target of rapamycin (mTORi) are components of systemic treatment in metastatic renal cell carcinoma (mRCC) and are applied in sequence. We compared the efficacy of VEGFRi and mTORi in 2nd line after failure of bevacizumab/interferon in a phase II trial. Methods: Key inclusion criteria were: measurable mRCC (all histologies), ECOG 0-1, IMDC risk: good or intermediate, adequate organ function. Tumor status was assessed in week 11 and q12 wks., thereafter. Measures of Health-related quality of life (HR-QoL) utilized FKSI-10 and was assessed in week 4, 10 and q12 wks., thereafter. 1st line consisted of bevacizumab 10mg/kg q2wks. + interferon 9*106 IE 3x/week (BEV/IFN). Upon progression or intolerance, patients were re-screened and randomized between VEGFRi (axitinib 5 mg BID, dose-escalation permitted; sunitinib 50 mg OD, 4-2 regimen) and everolimus (EVE) treatment (10 mg OD). Cross-over occurred at time of progression or intolerance. Improvement of 2nd line PFS-rate at 6 mo. from 50% to 65% was the primary endpoint. Secondary endpoints were PFS, total PFS, ORR, OS, safety and HR-QoL. Results: Between November 2012 and June 2015 a total of 22 of 100 patients were included and at that time stopped for poor accrual. 10 pts. (46%) were randomized to receive 2nd line treatment with everolimus (n = 5) or VEGFRi (n = 5). At study entry (2/10) 20% had nephrectomy. ECOG 0 was recorded in 20% (EVE) and 60% (VEGFRi), respectively. Objective response rate (ORR) to 1st line BEV/IFN was 20%. In 2nd line treatment all patients experienced adverse events (AE). Grade ≥3 AEs occurred in 2/5 (40%) (EVE) and 4/5 (80%) (VEGFRi) pts., respectively. SAEs occurred in 3/5 (60%) in each arm. ORR was 1/5 (20%) for axitinib and 0/5 (0%) for EVE. PFS rate at 180 days was 20% in each arm. Median PFS was 3.7 (EVE) and 2.2 mo. (VEGFRi) HR 1.0 (95%CI 0.26-3.85; p = 0.997). OS was comparable between arms HR 1.12 (95%CI 0.27-4.61; P = 0.872). 7 pts. crossed over to 3rd line treatment. Conclusions: The small number of pts. randomized to EVE or VEGFRi is a major limitation of our trial, but may mirror the current change of treatment reality. However, no significant difference was detected for the PFS rate at 6 mo., indicating the limited activity of EVE or VEGFRi in 2nd line treatment. Clinical trial information: NCT01731158.

High-dose bolus interleukin-2: Correlating response rate with number of doses received.

2013 ◽  
Vol 31 (6_suppl) ◽  
pp. 452-452
Author(s):  
Jolly Patel ◽  
Mayer N. Fishman ◽  
Dawn Goetz
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Metastatic Renal Cell Carcinoma ◽  
Cumulative Dose ◽  
Stable Disease ◽  
Renal Cell ◽  
Response Rate ◽  
Interleukin 2 ◽  
High Dose ◽  
Significant Difference

452 Background: Administration of high-dose interleukin-2 (IL-2) in metastatic renal cell carcinoma (MRCC) has higher response and survival rates when compared to low dose or subcutaneous administration. In patients who achieve a response, it may be at the expense of more toxicity risk, from more doses. The association of the major response rate with the number of high dose boluses or cumulative dose received is of interest. The primary objective of this study is to evaluate a direct correlation with response and cumulative dose or the total number of doses received. Methods: A retrospective chart review was conducted of all patients at H. Lee Moffitt Cancer Center diagnosed with metastatic renal cell carcinoma who received high dose bolus IL-2 from September 30th, 1999 to September 30th, 2010. The cumulative dose and the number of doses of IL-2 received was recorded and associated with categorical complete response [CR], partial response [PR], stable disease [SD] or progressive disease [PD] response, by treating physician assessment. Sites of metastasis were also documented. The incidence of adverse effects such as renal failure, transaminitis, cardiac arrhythmias, thrombocytopenia as well as rates of infection and ICU transfers were tabulated. Results: 31 out of 55 patients analyzed were assessed at least with stable disease in response to IL-2. Six achieved a CR, 11 achieved a PR, 14 had stable disease and 24 patients had PD as best responses. Among those with CR or PR to IL-2, they received approximately 30 doses of IL-2 (p=0.027 vs. those not in that category). Converesely, those who received a higher cumulative dose were also more likely to respond (p=0.0077). With respect to adverse events, 58% of patients experienced acute renal insufficiency, 63% transaminitis, 40% arrhythmias, and 45% thrombocytopenia. 55% required dopamine use at any point and 11% required use of additional pressors; 15% required an ICU transfer at some point, and approximately 4% developed a documented infection. Conclusions: Cumulative dose or number of high dose bolus doses received is associated with a statistically significant difference in response rate, within the limitations of this retrospective analysis.

scholarly journals Subcutaneous Interleukin-2 Monotherapy for Metastatic Renal Cell Carcinoma in Korean Patients

2021 ◽  
Vol 19 (4) ◽  
pp. 252-260
Author(s):  
Jeong Ho Kim ◽  
Ki Soo Lee ◽  
Choung-Soo Kim ◽  
Young Deuk Choi ◽  
Tae Hyo Kim
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Metastatic Renal Cell Carcinoma ◽  
Renal Cell ◽  
Subcutaneous Injection ◽  
Controlled Trial ◽  
Objective Response ◽  
Interleukin 2 ◽  
Korean Patients ◽  
Metastatic Rcc

Purpose: This study was a prospective single-arm clinical trial aimed at assessing the efficacy and toxicity of subcutaneous interleukin (IL)-2 monotherapy in patients with metastatic renal cell carcinoma (RCC).Materials and Methods: We enrolled 26 patients with metastatic RCC in this multicenter controlled trial. The patients received subcutaneous injections of recombinant IL-2 (BMI-rh-IL2, an aldesleukin biosimilar, BMIKOREA Co., Ltd.) in 5-week cycles. In the first week, the patients received a subcutaneous IL-2 loading dose of 18×106 IU once on treatment days 1–5, followed by 2 days of rest. In the following 3 weeks, they received a dose of 18×106 IU via subcutaneous injection once on treatment days 1 and 2. Then, the patients received a dose of 9×106 IU via subcutaneous injection once on treatment days 3, 4, and 5, followed by 2 days of rest. The primary end point was the objective response rate; the secondary end points were progressionfree survival (PFS) and safety.Results: Overall, 22 patients were included in the final per-protocol analysis. The objective response and the disease control rates were 13.64% (3 of 22), and 90.9% (20 of 22), respectively. The mean PFS was 5.55 months (95% confidence interval, 2.71–8.4). The proportion of patients who experienced a treatment-related grade 3 or 4 adverse event was 3.85% (1 of 26). There were no treatment-related deaths.Conclusions: In this study, the subcutaneous IL-2 monotherapy regimen demonstrated efficacy and safety comparable to those reported in previous studies of subcutaneous IL-2 monotherapy and was effective in Korean patients with metastatic RCC.

A Randomized Study of Low-Dose Interleukin-2 Subcutaneous Immunotherapy versus Interleukin-2 plus Interferon-Alpha as First Line Therapy for Metastatic Renal Cell Carcinoma

1993 ◽  
Vol 79 (6) ◽  
pp. 397-400 ◽  
Author(s):  
Paolo Lissoni ◽  
Sandro Barni ◽  
Antonio Ardizzoia ◽  
Marco Andres ◽  
Epifanio Scardino ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Interferon Alpha ◽  
Metastatic Renal Cell Carcinoma ◽  
Renal Cell ◽  
Response Rate ◽  
Interleukin 2 ◽  
Subcutaneous Immunotherapy ◽  
Significant Difference ◽  
Metastatic Rcc

Aims and Background IL-2 given subcutaneously in combination with interferon-alpha 2b (IFN) appears to induce a response rate comparable to that obtained with IL-2 intravenous injection in patients with metastatic renal cell carcinoma (RCC) but with lower toxicity. The role of IFN when combined with IL-2 has however still to be defined. The present study was performed to draw some preliminary conclusions about the effect of IFN in combination with IL-2 in metastatic RCC. Methods The study included 30 consecutive patients with metastatic RCC who were randomized to treatment with IL-2 subcutaneous therapy (3 million IU twice/daily for 5 days/week for 6 weeks) or with IL-2 plus IFN (5 million U/m2 subcutaneously thrice weekly). In patients without progressive disease, a second cycle was repeated after a 28-day rest period. Results No significant difference in partial response rate was found between patients treated with IL-2 alone and those given IL-2 plus IFN (5/15 vs 4/15). Similarly, no difference was seen in the percentage of stable disease (7/15 vs 7/15). Toxicity was higher in patients who received IL-2 plus IFN. Lymphocyte and eosinophil mean increase was higher in patients treated with IL-2 alone than in those treated with IL-2 plus IFN, without however any significant difference. Conclusions The present results, which require confirmation in a larger series, indicate that combination with IFN does not increase the efficacy of IL-2 subcutaneous immunotherapy in metastatic RCC but only the toxicity of treatment.

Sign in / Sign up

Export Citation Format

Share Document