High-dose Interleukin-2 Can Produce a High Rate of Response and Durable Remissions in Appropriately Selected Patients With Metastatic Renal Cancer

2011 ◽  
Vol 34 (1) ◽  
pp. 107-112 ◽  
Author(s):  
Alaaeldin Shablak ◽  
Kanwal Sikand ◽  
Jonathan H. Shanks ◽  
Fiona Thistlethwaite ◽  
Andrea Spencer-Shaw ◽  
...  
Keyword(s):  
Renal Cancer ◽  
Interleukin 2 ◽  
High Rate ◽  
High Dose ◽  
Metastatic Renal Cancer ◽  
Rate Of Response

Treatment of metastatic renal cancer with high-dose interleukin-2 after targeted therapy.

2012 ◽  
Vol 30 (5_suppl) ◽  
pp. 439-439 ◽  
Author(s):  
Robert E. Hawkins ◽  
Victoria Galvis ◽  
Jonathan Shanks ◽  
Neha Dalal ◽  
Fiona Thistlethwaite ◽  
...  
Keyword(s):  
Targeted Therapy ◽  
Complete Remission ◽  
Renal Cancer ◽  
Targeted Therapies ◽  
Interleukin 2 ◽  
High Dose ◽  
Consolidation Therapy ◽  
First Line ◽  
Metastatic Renal Cancer ◽  
Targeted Agent

439 Background: High-Dose Interleukin-2 (HD IL2) remains a good option for treatment of metastatic renal cancer. As a first-line treatment, in carefully selected patients, it can produce high rates of response ( OR 50%; CR 25%) (Shablak A et al., J Immunotherapy 2011, 34(1):107-122). Its use after targeted therapies is controversial and there are reports of increased toxicity, particularly an increased incidence of cardiovascular toxicity (and possibly a reduced response rate (Cho DC et al., J Immunotherapy 2009, 32(2):181-520). However, there is potential to use it either in patients who have failed treatment with targeted therapy or as a consolidation therapy after successful treatment with a targeted agent. Methods: Here we present the outcomes of 16 patients treated with first-line immunotherapy with HD-IL2 after targeted therapy: of these 8 had been treated after failure of 1-3 lines of targeted therapy and 8 have been treated as consolidation after initial response to sunitinib. The histological characteristics of the tumours all fitted into the “favourable” group as defined previously by us and all had high levels of expression of CAIX (> 80%). All had ECOG PS 0/1, a satisfactory baseline stress echo, an interval of at least 8 weeks from last dose of targeted agent to start of HD-IL2 and at most 2 organs of disease. Results: Toxicity is indistinguishable from that of patients without prior treatment and no patient needed inotropic support or admission to intensive care. The number of doses given per cycle was also similar to that in unpretreated patients. Overall the response rates are excellent – with 9/13 evaluable patients having RECIST defined response and 6/13 having a complete remission. To date none of the patients in complete remission have realpsed but follow up is relatively short with the longest being 24 months. The responses have been particularly striking following treatment with mTor inhibitors. Conclusions: Overall, HD IL2 can be given safely in carefully selected patients after targeted therapies. It appears to be effective as a salvage therapy and potentially as a consolidation therapy. Updated results will be presented.

Treatment of metastatic renal cancer

2017 ◽  
Author(s):  
Han Hsi Wong ◽  
Basma Greef ◽  
Tim Eisen
Keyword(s):  
Renal Cancer ◽  
Mammalian Target Of Rapamycin ◽  
Interleukin 2 ◽  
Second Line ◽  
Cytoreductive Nephrectomy ◽  
Second Line Therapy ◽  
Metastatic Renal Cancer ◽  
Treatment Paradigm ◽  
T Cell Regulation ◽  
Indolent Disease

Metastatic renal cancer is resistant to standard chemotherapy. Although some patients with indolent disease can be initially managed with observation, the majority of patients will require aggressive treatment soon after diagnosis. Options include cytoreductive nephrectomy, resection of a solitary metastasis in highly selected cases, or systemic therapy options. The TKIs sunitinib and pazopanib are currently the first-line treatments of choice. Whilst axitinib and cabozantinib have important roles in the second line the PD-1 checkpoint inhibitor, nivolumab, is now established as standard second line therapy. Inhibitors of the mammalian target of rapamycin (mTOR) pathway, everolimus and temsirolimus, interleukin-2 as well as the anti-angiogenic antibody bevacizumab have also been shown to be effective. The treatment paradigm of metastatic renal cancer is constantly changing as evidence from clinical trials continues to emerge. With the development of agents addressing novel targets such as T-cell regulation, the future certainly looks brighter for patients diagnosed with this disease.

Immunoendocrine Therapy with Interleukin-2 (IL-2) and Medroxyprogesterone Acetate (MPA): A Randomized Study with or without MPA in Metastatic Renal Cancer Patients during IL-2 Maintenance Treatment after Response or Stable Disease to IL-2 Subcutaneous Therapy

1993 ◽  
Vol 79 (4) ◽  
pp. 246-249 ◽  
Author(s):  
Paolo Lissoni ◽  
Sandro Barni ◽  
Gabriele Tancini ◽  
Fernando Brivio ◽  
Paolo Cardellini ◽  
...  
Keyword(s):  
Maintenance Therapy ◽  
Cancer Patients ◽  
Renal Cancer ◽  
Stable Disease ◽  
Medroxyprogesterone Acetate ◽  
Low Dose ◽  
Interleukin 2 ◽  
Cytotoxic Lymphocytes ◽  
Metastatic Renal Cancer ◽  
Significant Difference

Aims and Background It is known that interleukin-2 (IL-2) activated cytotoxic lymphocytes require a cell-cell contact to exert their anticancer action. Therefore, the pronounced fibrosis that generally characterizes the neoplastic mass could counteract the action of cytotoxic lymphocytes. Some preliminary studies have shown that progesterone and its analogs may inhibit fibroblast proliferation. On the basis of such evidence, we have designed a clinical study with or without the progestational agent medroxyprogesterone acetate (MPA) in metastatic renal cancer patients in maintenance therapy with IL-2 following response or stable disease (SD) after two cycles of IL-2 subcutaneous immunotherapy, in an attempt to evaluate the influence of MPA on free-from progression (FPP) period. Methods The study included 30 consecutive patients who were randomized to receive IL-2 alone (3 mllion IU twice/day for 5 days/month subcutaneously) or IL-2 plus low-dose MPA (500 mg orally one day/week) without interruption until disease progression. Results A FPP period longer than 1 year was obtained in 8/14 patients treated with IL-2 plus MPA and in only 3/16 patients treated with IL-2 alone. The difference was statistically significant. On the contrary, no significant difference was seen in the mean number of lymphocytes and eosinophils, which was evaluated monthly. Finally, no hyperglycemic or thromboembolic complications occurred in patients concomitantly treated with MPA. Conclusions This preliminary study would suggest that the concomitant administration of low-dose MPA may prolonge the FFP period in metastatic renal cancer patients under maintenance therapy with IL-2. A longer follow-up will be required to evaluate the influence of MPA on overall survival.

Randomized Study of Intravenous versus Subcutaneous Interleukin-2, and IFNα in Patients with Good Prognosis Metastatic Renal Cancer

2008 ◽  
Vol 14 (18) ◽  
pp. 5907-5912 ◽  
Author(s):  
Sylvie Négrier ◽  
David Perol ◽  
Alain Ravaud ◽  
Jacques O. Bay ◽  
Stéphane Oudard ◽  
...  
Keyword(s):  
Renal Cancer ◽  
Randomized Study ◽  
Interleukin 2 ◽  
Good Prognosis ◽  
Metastatic Renal Cancer

scholarly journals Durable responses and reversible toxicity of high-dose interleukin-2 treatment of melanoma and renal cancer in a Community Hospital Biotherapy Program

2014 ◽  
Vol 2 (1) ◽  
pp. 13 ◽  
Author(s):  
Roxanne Payne ◽  
Lyn Glenn ◽  
Helena Hoen ◽  
Beverley Richards ◽  
John W Smith ◽  
...  
Keyword(s):  
Renal Cancer ◽  
Community Hospital ◽  
Interleukin 2 ◽  
High Dose

scholarly journals Randomized Study of High-Dose and Low-Dose Interleukin-2 in Patients With Metastatic Renal Cancer

2003 ◽  
Vol 21 (16) ◽  
pp. 3127-3132 ◽  
Author(s):  
James C. Yang ◽  
Richard M. Sherry ◽  
Seth M. Steinberg ◽  
Suzanne L. Topalian ◽  
Douglas J. Schwartzentruber ◽  
...  
Keyword(s):  
Overall Survival ◽  
Low Dose ◽  
Performance Status ◽  
Randomized Study ◽  
Cell Cancer ◽  
Interleukin 2 ◽  
Complete Response ◽  
High Dose ◽  
Metastatic Renal Cancer ◽  
Survival Difference

Purpose: This three-arm randomized study compares response rates and overall survival of patients with metastatic renal cell cancer (RCC) receiving high-dose or one of two low-dose interleukin-2 (IL-2) regimens. Patients and Methods: Patients with measurable metastatic RCC and a good performance status were randomized to receive either 720,000 U/kg (high-dose [HD]) or 72,000 U/kg (low-dose [LD]), both given by intravenous (IV) bolus every 8 hours. After randomly assigning 117 patients, a third arm of low-dose daily subcutaneous IL-2 was added, and an additional 283 patients were randomly assigned. Results: A total of 156 patients were randomly assigned to HD IV IL-2, and 150 patients to LD IV IL-2. Toxicities were less frequent with LD IV IL-2 (especially hypotension), but there were no IL-2-related deaths in any arm. There was a higher response proportion with HD IV IL-2 (21%) versus LD IV IL-2 (13%; P = .048) but no overall survival difference. The response rate of subcutaneous IL-2 (10%, partial response and complete response) was similar to that of LD IV IL-2, differing from HD IV (P = .033). Response durability and survival in completely responding patients was superior with HD IV compared with LD IV therapy (P = .04). Conclusion: Major tumor regressions, as well as complete responses, were seen with all regimens tested. IL-2 was more clinically active at maximal doses, although this did not produce an overall survival benefit. The immunological factors which constrain the curative potential of IL-2 to only a small percentage of patients need to be further elucidated.

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