High-dose Interleukin-2 Therapy for Metastatic Renal Cell Carcinoma: A Contemporary Experience

Hanzly, Michael; Aboumohamed, Ahmed; Nancharaiah, Y.V.; Creighton, Terrance; DiGiorgio, Lorenzo; Fredrick, Ariel; Rao, Gaurav; Mehedint, Diana; George, Saby; Attwood, Kristopher; Kauffman, Eric; Narashima, Deepika; Khushalani, Nikhil I.; Пили, Роберто; Schwaab, Thomas

doi:10.1016/j.urology.2014.02.005

Cited by 24 publications

(19 citation statements)

References 22 publications

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“…A retrospective analysis performed at Providence Portland Cancer Center, which included 314 mM and 186 mRCC patients treated between 1997 and 2012, reported an objective response rate (ORR) of 28 % for mM and 24 % for mRCC patients [5]. In a study of 88 mRCC patients treated at Roswell Park between 2004 and 2011, the observed mOS was 35.5 months compared to historical reference range of 16–20 months [6]. In a prospective multicenter study conducted by the Cytokine Working Group, researchers reported an ORR of 25 % and mOS of 42.8 months in 120 mRCC patients treated between 2006 and 2009 [7].…”

Section: Introductionmentioning

confidence: 99%

Contemporary experience with high-dose interleukin-2 therapy and impact on survival in patients with metastatic melanoma and metastatic renal cell carcinoma

Alva

Daniels

Wong

et al. 2016

Cancer Immunol Immunother

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High-dose interleukin-2 (HD IL-2) was approved for treatment of metastatic renal cell carcinoma (mRCC) in 1992 and for metastatic melanoma (mM) in 1998, in an era predating targeted therapies and immune checkpoint inhibitors. The PROCLAIMSM registry was established to collect and analyze data for patients treated with HD IL-2 in the current era. This analysis includes 170 patients with mM and 192 patients with mRCC treated between 2005 and 2012 with survival data current as of July 27, 2015. For patients with mM, complete response (CR) was observed in 5 %, partial response (PR) in 10 %, stable disease (SD) in 22 %, and 63 % had progressive disease (PD). The median overall survival (mOS) for these patients was 19.6 months, with a median follow-up of 43.1 months. The mOS was not reached for patients achieving CR or PR, and was 33.4 months for patients with SD. For patients with mRCC, 6 % achieved CR, 9 % had PR, 22 % had SD, and 62 % had PD. The mOS was 41 months, with a median follow-up of 46.6 months. The mOS for patients who had CR and PR was not reached and was 49.6 months for patients with SD. There were no treatment-related deaths among 362 patients. The duration of mOS for patients with mM and mRCC is longer than historically reported. These data support a continued role for IL-2 in the treatment of eligible patients with mM or mRCC and warrant further evaluation of HD IL-2 in combination or sequence with other therapeutic agents.Electronic supplementary materialThe online version of this article (doi:10.1007/s00262-016-1910-x) contains supplementary material, which is available to authorized users.

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Section: Introductionmentioning

confidence: 99%

Contemporary experience with high-dose interleukin-2 therapy and impact on survival in patients with metastatic melanoma and metastatic renal cell carcinoma

Alva

Daniels

Wong

et al. 2016

Cancer Immunol Immunother

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“…One treatment cycle was defined as 2 hospital admissions for HD IL-2 within a 30-day period. The dosing schedule for HD IL-2 therapy was defined as intravenous infusion every 8 hours over 15 minutes on days 1 through 5 and days 15 through 19, with a maximum of 12 to 15 doses per admission and 2 admissions constituting a single treatment cycle [5,8]. Up to 3 treatment cycles, each separated by 6 to 8 weeks, are usually recommended for patients who demonstrate a response and tolerate treatment [14].…”

Section: Methodsmentioning

confidence: 99%

“…It can elicit complete responses in 5% to 10% of patients [2–5]. However, its use is limited by the high rate of severe acute toxicities and the need for experienced staff to administer it [5–8]. …”

Section: Introductionmentioning

confidence: 99%

Contemporary trends in high-dose interleukin-2 use for metastatic renal cell carcinoma in the United States

Allard

Gelpi-Hammerschmidt

Harshman

et al. 2015

Urologic Oncology: Seminars and Original Investigations

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Background Targeted therapies (TTs) have revolutionized metastatic renal cell carcinoma (mRCC) treatment in the past decade, largely replacing immunotherapy including high-dose interleukin-2 (HD IL-2) therapy. We evaluated trends in HD IL-2 use for mRCC in the TT era. Methods Our cohort comprised a weighted estimate of all patients undergoing HD IL-2 treatment for mRCC from 2004 to 2012 using the Premier Hospital Database. We assessed temporal trends in HD IL-2 use including patient, disease, and hospital characteristics stratified by era (pre-TT uptake: 2004–2006, uptake: 2007–2009, and post-TT uptake: 2010–2012) and fitted multivariable regression models to identify predictors of treatment toxicity and tolerability. Results An estimated 2,351 patients received HD IL-2 therapy for mRCC in the United States from 2004 to 2012. The use decreased from 2004 to 2008. HD IL-2 therapy became increasingly centralized in teaching hospitals (24% of treatments in 2004 and 89.5% in 2012). Most patients who received HD IL-2 therapy were men, white, younger than 60 years, had lung metastases, and were otherwise healthy. Vasopressors, intensive care unit admission, and hemodialysis were necessary in 53.4%, 33.0%, and 7.1%, respectively. Factors associated with toxicities in multivariable analyses included being unmarried, male sex, and multiple metastatic sites. African Americans and patients with single-site metastases were less likely to receive multiple treatment cycles. Conclusions HD IL-2 therapy is used infrequently for mRCC in the United States, and its application has diminished with the uptake of TT. Patients are being increasingly treated in teaching hospitals, suggesting a centralization of care and possible barriers to access. A recent slight increase in HD IL-2 therapy use likely reflects recognition of the inability of TT to effect a complete response.

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“…Roswell Park Cancer Institute reported their experience for 91 patients who were treated with high-dose IL-2. The overall response rate was 16% with no treatment-related mortality (29). Payne et al reported the experience from the Earle A Chiles Research Institute for 186 patients with advanced renal cell cancer treated with high-dose IL-2.…”

Section: High Dose Il-2 – Contemporary Experience: “Proclaim”mentioning

confidence: 99%

Interleukin-2 in Renal Cell Carcinoma: A Has-Been or a Still-Viable Option?

Amin

White

2014

jkcvhl

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Modulation of the immune response plays an important role in the natural history of renal cell carcinoma. Spontaneous regression of metastases has been well documented in a small percentage of patients after they undergo de-bulking nephrectomy without any additional systemic intervention. The only logical explanation for these observations is “resetting” of the balance between tumor and the host immune system that, having been overwhelmed by the tumor burden, is able to function better after tumor de-bulking. Attempts to modulate the activity of the immune system “on demand” have included the use of vaccines, cytokines/lymphokines, adoptive cell transfer, monoclonal antibodies and most recently manipulation of immune checkpoint inhibitors. Here we review the data for infusional interleukin-2 in the management of advanced renal cell carcinoma and its role in current clinical practice.

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High-dose Interleukin-2 Therapy for Metastatic Renal Cell Carcinoma: A Contemporary Experience

Cited by 24 publications

References 22 publications

Contemporary experience with high-dose interleukin-2 therapy and impact on survival in patients with metastatic melanoma and metastatic renal cell carcinoma

Contemporary experience with high-dose interleukin-2 therapy and impact on survival in patients with metastatic melanoma and metastatic renal cell carcinoma

Contemporary trends in high-dose interleukin-2 use for metastatic renal cell carcinoma in the United States

Interleukin-2 in Renal Cell Carcinoma: A Has-Been or a Still-Viable Option?

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