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.

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.

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.

Prolonged continuous intravenous infusion interleukin-2 and lymphokine-activated killer-cell therapy for metastatic renal cell carcinoma.

1992 ◽  
Vol 10 (6) ◽  
pp. 960-968 ◽  
Author(s):  
J A Thompson ◽  
K L Shulman ◽  
M C Benyunes ◽  
C G Lindgren ◽  
C Collins ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Metastatic Renal Cell Carcinoma ◽  
Renal Cell ◽  
Response Rate ◽  
Interleukin 2 ◽  
Maintenance Phase ◽  
Lak Cells ◽  
Total Response ◽  
Total Response Rate

PURPOSE Two consecutive protocols of continuous intravenous (CIV) infusion interleukin-2 (IL-2) and lymphokine-activated killer (LAK) cells were carried out in patients with metastatic renal cell carcinoma (RCC) to determine the response rate and toxicity. PATIENTS AND METHODS In both protocols, patients received induction IL-2 at 6 x 10(6) U/m2/d on days 1 to 5, and underwent leukapheresis on days 7 to 9 at the peak of rebound lymphocytosis. LAK cells were generated by a 5-day incubation with IL-2 at 1,000 U/mL, and were infused on days 12 to 14. For the first 20 patients (protocol A), maintenance IL-2 was administered at 6 x 10(6) U/m2/d on days 12 to 16. On the assumption that less IL-2 might be required to maintain rather than to induce LAK activity, and that a longer duration of maintenance IL-2 might enhance LAK survival and function in vivo, the protocol for the subsequent 22 patients (protocol B) was altered so that the maintenance phase consisted of a lower dose of IL-2 (2 x 10(6) U/m2/d) administered for a longer period of time (days 10 to 20). RESULTS In protocol A, there were two complete responses (CRs) and three partial responses (PRs), for a total response rate of 25%. One PR was surgically converted into a CR. The durations of the CRs are 36+, 18+, and 18+ months. Hypotension and capillary leak were most severe during maintenance, which limited the median duration of maintenance IL-2 to 4 days. In protocol B, no patient experienced severe hypotension, and the median duration of maintenance IL-2 was 9 days. Two patients exhibited a CR and seven a PR, for a total response rate of 41%. Two PRs were surgically converted to CRs. The durations of CR are 14+, 9+, 6+, and 5+ months. In both protocols, the CIV induction regimen resulted in marked rebound lymphocytosis (mean, 11,097/microL) and LAK-cell yield (mean, 18.1 x 10(10)). The cumulative response rate was 14 of 42 patients, or 33% (95% confidence interval, 19% to 47%). CONCLUSION These results demonstrate that both protocols of CIV IL-2 plus LAK cells have substantial antitumor activity, and that a longer maintenance phase of IL-2 at a lower dose is associated with significantly less toxicity without a loss of therapeutic efficacy.

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.

Randomized comparison of high-dose and low-dose intravenous interleukin-2 for the therapy of metastatic renal cell carcinoma: an interim report.

1994 ◽  
Vol 12 (8) ◽  
pp. 1572-1576 ◽  
Author(s):  
J C Yang ◽  
S L Topalian ◽  
D Parkinson ◽  
D J Schwartzentruber ◽  
J S Weber ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Metastatic Renal Cell Carcinoma ◽  
Renal Cell ◽  
Low Dose ◽  
Interleukin 2 ◽  
High Dose ◽  
Intravenous Bolus ◽  
To Receive ◽  
Metastatic Rcc

PURPOSE A randomized prospective study was performed to compare the efficacy and toxicity of high-dose intravenous bolus interleukin-2 (IL-2) and a lower-dose intravenous bolus regimen for the treatment of metastatic renal cell carcinoma (RCC). PATIENTS AND METHODS Between March 1991 and April 1993, 125 patients with metastatic RCC were randomized to receive IL-2 by intravenous bolus every 8 hours at either 720,000 IU/kg (high-dose) or 72,000 IU/kg (low-dose) to the maximum-tolerated number of doses (or a maximum of 15 doses). After approximately 7 to 10 days, both treatment groups were re-treated with a second identical cycle of therapy. Those patients who were stable or responding to treatment 5 to 6 weeks later went on to receive re-treatment with another course (two cycles) of therapy. Response rates and toxicity were determined for the two treatment arms. RESULTS One hundred twenty-five patients received a total of 208 courses of therapy. Sixty patients were randomized to receive low-dose, and 65 to receive high-dose IL-2. There were no treatment-related deaths in either arm. There was a greater incidence of grade III or IV thrombocytopenia, malaise, and hypotension in patients who received high-dose IL-2, while patients who received low-dose IL-2 had significantly more infections. Three percent of treatment courses with low-dose IL-2 required vasopressor support, compared with 52% of courses with high-dose IL-2. Patients who received low-dose IL-2 had a 7% complete response (CR) and an 8% partial response (PR) rate, and patients who received high-dose IL-2 had a 3% CR and a 17% PR rate. CONCLUSION Low-dose intravenous bolus IL-2 represents an effective regimen for the treatment of metastatic RCC, with preliminary results comparable to those observed with high-dose IL-2. Low-dose IL-2 can be administered with significantly fewer complications, reduced use of vasopressor support, and fewer admissions to an intensive care unit (ICU).

Multicenter phase II trial of interleukin-2, interferon-alpha, and 13-cis-retinoic acid in patients with metastatic renal-cell carcinoma.

1998 ◽  
Vol 16 (5) ◽  
pp. 1820-1825 ◽  
Author(s):  
W M Stadler ◽  
T Kuzel ◽  
M Dumas ◽  
N J Vogelzang
Keyword(s):  
Renal Cell Carcinoma ◽  
Retinoic Acid ◽  
Cell Carcinoma ◽  
Median Survival ◽  
Interferon Alpha ◽  
Metastatic Renal Cell Carcinoma ◽  
Renal Cell ◽  
Performance Status ◽  
Interleukin 2 ◽  
Minor Response

PURPOSE To determine the response rate and toxicity of oral 13-cis-retinoic acid (CRA) added to an outpatient regimen of subcutaneous interleukin-2 (IL2) and interferon-alpha (IFNA) in previously untreated patients with metastatic renal-cell carcinoma (RCC). PATIENTS AND METHODS Eligibility included a performance status of 2 or better, no significant end-organ dysfunction, and written informed consent. Characteristics of 47 of 48 assessable patients included a median performance status of 0, prior nephrectomy in 68% of patients, one metastatic site in 30% of patients, and lung-only metastatic disease in 21% of patients. Therapy consisted of IL2 11 x 10(6) IU 4 days per week for 4 weeks, IFNA 9 x 10(6) IU 2 days per week for 4 weeks, and CRA 1 mg/kg daily on a 6-week cycle. RESULTS Eight of 47 patients (17%) responded (one complete response, seven partial responses). Three partial responders were rendered disease free by subsequent surgical resection. Four additional patients experienced a minor response in lung or soft tissue metastases. The median duration of response, which included minor responses, was 42 weeks, and median survival was 74 weeks (17 months). Grades 3 or greater toxicities during the first cycle included flu-like symptoms (21% of patients), fatigue (6% of patients), and nausea and vomiting (15% of patients). Significant cumulative toxicities were hyperlipidemia (four of 18 patients), and cardiomyopathy (one of 18 patients). There was one therapy-related death. CONCLUSION Outpatient CRA plus IL2 and IFNA is feasible and modestly effective in metastatic RCC. The prolonged median survival is encouraging, but randomized trials are required to show that the combination represents an improvement over single-agent immunotherapy.

Sign in / Sign up

Export Citation Format

Share Document