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.

High dose interleukin-2 and response in 944 patients with metastatic renal cell cancer (RCC): Data from the PROCLAIM registry.

2018 ◽  
Vol 36 (6_suppl) ◽  
pp. 624-624
Author(s):  
Tanya B. Dorff ◽  
Michael K.K. Wong ◽  
Joseph Clark ◽  
Gregory A. Daniels ◽  
Brendan D. Curti ◽  
...  
Keyword(s):  
Progressive Disease ◽  
Collecting Duct ◽  
Cell Cancer ◽  
Interleukin 2 ◽  
Dose Intensity ◽  
Complete Response ◽  
Outcome Data ◽  
High Dose ◽  
Chi Square ◽  
Prior Therapy

624 Background: High dose interleukin-2 (HD IL2) has traditionally been dosed every 8 hours for a maximum of 14 doses each cycle. We evaluated whether alternate dosing schedules and dose intensity affected achievement of complete response (CR) or partial response (PR) in the PROCLAIM registry. Methods: Patients with metastatic RCC were enrolled retrospectively and prospectively into the PROCLAIM registry to collect outcome data. Statistical methods for comparisons were done using Fisher’s and Chi Square tests. Results: From 2006-2017 the registry included 944 RCC patients; 257 (27%) women, 676 (72%) men. 844 (89%) were white. Histologic distribution: 624 (66%) clear cell, 93 (10%) medullary, 79 (8%) collecting duct, 78 (8%) chromophobe and 70 (7%) papillary. 207 (22%) had prior therapy with VEGF/mTOR. Best response was 51 (5.4%) CR and 169 (17.9%) PR; 263 (28%) progressive disease. 13 (1.4%) patients received q12 hour dosing while 830 (88%) received q8 hour dosing. 608 (64%) received 600 KIU/kg and 67 (7%) received 720 KIU/kg. Median # of doses in cycle 1 was 10 for CR and PR patients at 600 KIU/kg and 9 for those with stable or progressive disease. In the 720 KIU/kg group median #doses was 11 for CR, 8 for PR, and 7 for stable or progressive disease. In cycle 2 median doses received was 7.16 for patients with CR, 7.02 for PR and 6.76 for stable disease. Median dose intensity is similar at these two dose levels. Associations with achievement of CR/PR are summarized in the Table. Conclusions: There is no difference in response rate based on dosing schedule but the small number of subjects dosed q12 hours limits interpretation. Good performance patients possess the best opportunity for benefit from HD IL2. There is a trend for response with higher median # doses. Further studies of alternate dosing schedules are warranted. Clinical trial information: NCT01415167. [Table: see text]

Improved Survival in Patients with Peripheral T Cell Lymphoma, Unspecified Following High-Dose Therapy and Stem Cell Transplantation: A Retrospective Review of a Single Institution’s Experience.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 3062-3062
Author(s):  
Ryan A. Wilcox ◽  
Ahmet Dogan ◽  
Kay Ristow ◽  
Joseph P. Colgan ◽  
Thomas M. Habermann ◽  
...  
Keyword(s):  
Overall Survival ◽  
Stem Cell ◽  
Performance Status ◽  
Complete Response ◽  
High Dose ◽  
High Dose Therapy ◽  
Ecog Performance Status ◽  
First Response ◽  
Hodgkin's Lymphomas ◽  
Disease Free

Abstract Background: Peripheral T-cell non-Hodgkin’s lymphomas (PTCL) account for approximately 10% of all non-Hodgkin’s lymphomas in the U.S. and Europe. PTCL, unspecified (PTCL-U), as classified by the WHO, is the most common subtype. The ability of high-dose therapy (HDT) and stem cell transplantation (SCT) to improve patient outcome was evaluated in the current study. Methods: All patients with PTCL-U evaluated at our institution who had tissue specimens available for review from January, 1994 to December, 2005 were identified and both clinical characteristics and treatment course obtained from the medical record. Results: 89 patients with PTCL-U were identified, with a median follow up of 13 months (range 1 month–12 years). The median age at diagnosis was 56 years (range 24–90). The IPI was low, intermediate or high in 34%, 44% and 22% of patients, respectively. On univariate analysis, age >60 (p<.0001), ECOG performance status >1 (p<.0001), LDH greater than normal (p=.004), Ann Arbor Stage III/IV (p=.01) and the presence of B symptoms (p=.0004) were associated with a poorer overall survival, as was an intermediate or high IPI (p<.0001). In contrast, on multivariate analysis only age >60 (p=.0006) and ECOG performance status >1 (p=.007) were independently associated with poorer overall survival. Fifty-seven percent of patients were treated initially with an anthracycline-based regimen, most commonly CHOP (53%). Patients with a low (0–1), intermediate (2–3) or high (4–5) IPI experienced a 61%, 29% and 18% 5-year overall survival, respectively. Fourteen patients (16%) received HDT and autologous (n=12) or allogeneic (n=2) SCT, either at the time of a first partial or complete response (n=11) or at the time of first relapse (n=3). The median survival in those patients treated initially with an anthracycline-based regimen alone was 11 months (95% CI 0.6–1.6 years). Improvement in both 5-year overall (75% vs 24%, HR=5.6, 95% CI 2.0–23.4, p=.0004) and disease-free (60% vs 26%, HR=3.2, 95% CI 1.3–9.3, p=.008) survival was observed in patients who received HDT/SCT, as compared to patients treated with anthracycline-based therapy alone. Furthermore, improvement in both 5-year overall (80% vs 26%, HR=5.8, 95% CI 1.7–35.7, p=.002) and disease free (72% vs 26%, HR=3.8, 95% CI 1.3–15.8, p=.009) survival was observed in patients who received HDT/SCT at the time of a first partial or complete response when compared to patients who received anthracycline-based therapy. When patients who failed to achieve a first partial or complete response were excluded from the analysis, improved 5-year overall (80% vs 57%, HR=0.5, 95% CI 0.1–2.1, p=.4) and disease-free (72% vs 53%, HR=0.7, 95% CI 0.1–2.3, p=.5) survival were observed in patients who received upfront HDT/SCT, although this failed to reach statistical significance. The improved overall and disease free survival observed in patients receiving HDT/SCT, either at the time of a first response or at the time of relapse, remained significant when accounting for differences in the IPI. In conclusion, selected patients with PTCL-U may benefit from treatment with HDT/SCT following a first response to conventional anthracycline-based chemotherapy.

Overall survival (OS) by clinical risk category for high dose interleukin-2 (HD IL-2) treated metastatic renal cell cancer (RCC): Data from PROCLAIM.

2018 ◽  
Vol 36 (15_suppl) ◽  
pp. 4578-4578
Author(s):  
Mayer N. Fishman ◽  
Joseph I Clark ◽  
Ajjai Shivaram Alva ◽  
Brendan D. Curti ◽  
Neeraj Agarwal ◽  
...  
Keyword(s):  
Overall Survival ◽  
Renal Cell Cancer ◽  
Renal Cell ◽  
Cell Cancer ◽  
Interleukin 2 ◽  
Risk Category ◽  
High Dose ◽  
Clinical Risk ◽  
Metastatic Renal Cell Cancer

Multiinstitutional phase II trial of intensive combination chemoimmunotherapy for metastatic melanoma.

1994 ◽  
Vol 12 (8) ◽  
pp. 1553-1560 ◽  
Author(s):  
M B Atkins ◽  
K R O'Boyle ◽  
J A Sosman ◽  
G R Weiss ◽  
K A Margolin ◽  
...  
Keyword(s):  
Metastatic Melanoma ◽  
Performance Status ◽  
Objective Response ◽  
Eastern Cooperative Oncology Group ◽  
Interleukin 2 ◽  
Complete Response ◽  
Phase Iii ◽  
Survival Duration ◽  
High Dose ◽  
Ecog Performance Status

PURPOSE To evaluate the activity and toxicity of combined high-dose cisplatin, dacarbazine (DTIC), and tamoxifen chemotherapy and high-dose bolus interleukin-2 (IL-2) in patients with metastatic melanoma. PATIENTS AND METHODS Patients with metastatic melanoma, Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1, and normal organ function were enrolled onto this multiinstitutional Cytokine Working Group trial. Patients received intensive chemoimmunotherapy consisting of cisplatin (50 mg/m2) and DTIC (350 mg/m2) intravenously (IV) on days 1 to 3 and 43 to 45, IL-2 600,000 IU/kg IV every 8 hours on days 12 to 16 and 26 to 30 (maximum, 28 doses), and tamoxifen 20 mg orally each day. Patients were evaluated for response at day 63 of each cycle, and responding patients were given a second cycle of therapy beginning on day 71 to 85. RESULTS Thirty-eight patients were entered onto this study. Toxicities were as expected for the chemotherapy and immunotherapy components of this regimen. Overlapping toxicity consisted primarily of thrombocytopenia (76% of patients required platelet transfusions), neutropenia, anemia, fatigue, and weight loss. Despite these cytopenias, bleeding and infectious complications were rare. There were no treatment-related deaths. Three patients achieved a complete response (CR; 8%), and 13 achieved a partial response (PR). The overall objective response rate was 42% (95% confidence interval [CI], 26% to 58%). Six additional patients had greater than 50% tumor reduction at day 63, which did not persist until a subsequent evaluation. The median duration of response was 5 months (range, 2 to 20+), and the median survival duration was 11 months. CONCLUSION This intensive treatment regimen appears to possess activity in metastatic melanoma comparable, but not superior, to that of other less intensive cisplatin- and IL-2-based chemoimmunotherapy regimens. Although the toxicity and complexity of this regimen make it unsuitable for phase III testing and impractical for more widespread use, the results of this study support a potential favorable interaction between IL-2 and chemotherapy in this disease and highlight the need for appropriately designed phase III trials.

Adoptive cell therapy for melanoma patients using tumor-infiltrating lymphocytes, lymphodepleting chemotherapy, and low-dose interleukin-2.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 2574-2574
Author(s):  
Eva Ellebaek ◽  
Trine Zeeberg Iversen ◽  
Niels Junker ◽  
Marco Donia ◽  
Lotte Engell-Noerregaard ◽  
...  
Keyword(s):  
Cell Therapy ◽  
Low Dose ◽  
Adoptive Cell Therapy ◽  
Pilot Trial ◽  
Interleukin 2 ◽  
Tumor Infiltrating Lymphocytes ◽  
Complete Response ◽  
High Dose ◽  
Autologous Tumor ◽  
Infiltrating Lymphocytes

2574 Background: Adoptive T cell therapy is based on isolation of tumor infiltrating lymphocytes (TIL) from autologous tumor, in vitro activation and expansion, and the reinfusion of these cells into a lymphodepleted patient. Together with high-dose interleukin (IL)-2 this treatment has in a few other countries successively been given to patients with advanced malignant melanoma and an impressive 50% response rate has been observed. Here we report the experience from a Danish Translational Research Center using low-dose subcutaneous IL-2 injections. Methods: A pilot trial including patients with metastatic melanoma, PS ≤1, age <70, measurable and progressive disease, and no CNS involvement. Six patients were treated with lymphodepleting chemotherapy, TIL infusion, and 14 days of low-dose IL-2, 2 MIU/day. Results: Low-dose IL-2 considerably decreased the toxicity of the treatment with no grade 3-4 events related to this drug. Two of the 6 treated patients have an ongoing complete response (30+ and 7+ months), 2 patients had stable disease (4.5 and 5 months) and 2 patients progressed shortly after treatment. Five patients went through surgery but were not treated because of rapid disease progression (2), development of brain metastases (2) or the inability to grow cells (1). Tumor-reactivity of the infused cells and peripheral monocytes before and after therapy were analyzed. High tumor responses in the infusion products were correlated to clinical response and also an induction of tumor reactive T cells were seen in the peripheral blood for 1 patient in complete response. Conclusions: Complete and durable responses are induced after treatment with adoptive cell transfer in combination with low-dose IL-2 questioning the need for high and toxic doses of IL-2.

scholarly journals Randomized phase II study of stereotactic body radiotherapy and interleukin-2 versus interleukin-2 in patients with metastatic melanoma

2020 ◽  
Vol 8 (1) ◽  
pp. e000773 ◽  
Author(s):  
Brendan Curti ◽  
Marka Crittenden ◽  
Steven K Seung ◽  
Christopher B Fountain ◽  
Roxanne Payne ◽  
...  
Keyword(s):  
Metastatic Melanoma ◽  
Randomized Study ◽  
Objective Response ◽  
Interleukin 2 ◽  
Evaluation Criteria ◽  
Response Assessment ◽  
Complete Response ◽  
High Dose ◽  
Randomized Phase Ii ◽  
Registration Number

BackgroundA pilot study of stereotactic body radiation therapy (SBRT) followed by high-dose interleukin-2 (IL-2) showed a higher than anticipated objective response rate (ORR) among patients with metastatic melanoma (MM). We performed a prospective randomized study to determine if the ORR of SBRT + IL-2 was greater than IL-2 monotherapy in patients with advanced melanoma.MethodsPatients with MM who had adequate physiological reserve for IL-2 and at least one site suitable for SBRT were eligible. There was a 1:1 randomization to SBRT + IL-2 or IL-2 monotherapy. Patients received one or two doses of SBRT (20 Gy per fraction) with the last dose administered 3 days before starting the first cycle of IL-2. IL-2 (600,000 IU per kg via intravenous bolus infusion) was given every 8 hours for a maximum of 14 doses with a second cycle after a 2-week rest. Responding patients received up to six IL-2 cycles. Patients assigned to IL-2 monotherapy who exhibited progression of melanoma after cycle 2 were allowed to crossover and receive SBRT and additional IL-2. Response Evaluation Criteria in Solid Tumors 1.1 criteria were applied to non-irradiated lesions for response assessment.Results44 patients were included in the analysis. The ORR in the SBRT + IL-2 group was 54%: 21% complete response (CR), 33% partial response (PR), 21% stable disease (SD) and 25% progressive disease (PD). The ORR in patients receiving IL-2 monotherapy was 35%: 15% CR, 20% PR, 25% SD and 40% PD. Seven patients assigned to IL-2 subsequently received SBRT + IL-2. One CR and two PRs were observed in the crossover group. There was no difference in progression-free or overall survival (OS). At 5 years the OS was 26% in the SBRT + IL-2 group and 25% in the IL-2 monotherapy group. The disease control rate (DCR) was higher in the SBRT + IL-2 group (75% vs 60%, p=0.34).ConclusionsSBRT + IL-2 induced more objective responses with a higher DCR compared to IL-2 monotherapy in MM. IL-2 monotherapy resulted in a significantly higher ORR than anticipated. Some patients in the crossover group also achieved objective responses.Trial registration numberNCT01416831.

High-dose versus low-dose vinblastine in cisplatin-vinblastine-bleomycin combination chemotherapy of non-seminomatous testicular cancer: a randomized study of the EORTC Genitourinary Tract Cancer Cooperative Group.

1986 ◽  
Vol 4 (8) ◽  
pp. 1199-1206 ◽  
Author(s):  
G Stoter ◽  
D T Sleyfer ◽  
W W ten Bokkel Huinink ◽  
S B Kaye ◽  
W G Jones ◽  
...  
Keyword(s):  
Testicular Cancer ◽  
Low Dose ◽  
Randomized Study ◽  
Complete Response ◽  
High Dose ◽  
Tract Cancer ◽  
Receive Induction Chemotherapy ◽  
Significant Difference ◽  
To Receive ◽  
Disease Free

Two hundred fourteen patients with disseminated non-seminomatous testicular cancer were randomized to receive induction chemotherapy with cisplatin, vinblastine, and bleomycin (PVB). The randomization was for vinblastine 0.4 mg/kg/cycle or 0.3 mg/kg/cycle. The complete response (CR) rates to both regimens were identical: 68% and 71%, respectively. In addition, there was no significant difference in disease-free and overall survival. There was a significant decrease in the incidence of WBC nadirs below 1,000/microL: 29% and 13%, respectively (P = .01). Of the non-hematologic toxicities, there was a significant reduction in the incidence of mucositis: 53% and 37%, respectively (P = .006). The major prognostic factor was tumor volume. This study confirms that vinblastine 0.3 mg/kg/cycle in PVB chemotherapy is as effective and less toxic than vinblastine 0.4 mg/kg/cycle.

Interleukin-2 and lymphokine-activated killer cell therapy of solid tumors: analysis of toxicity and management guidelines.

1989 ◽  
Vol 7 (4) ◽  
pp. 486-498 ◽  
Author(s):  
K A Margolin ◽  
A A Rayner ◽  
M J Hawkins ◽  
M B Atkins ◽  
J P Dutcher ◽  
...  
Keyword(s):  
Phase Ii ◽  
Performance Status ◽  
Cell Cancer ◽  
Killer Cell ◽  
Interleukin 2 ◽  
Ventilatory Support ◽  
High Dose ◽  
Phase Ii Trials ◽  
Organ Function ◽  
Life Threatening

The National Cancer Institute (NCI) Extramural IL2/LAK Working Group treated 93 patients with 114 cycles of high-dose intravenous (IV) interleukin-2 (IL-2) and lymphokine-activated killer (LAK) cells in three phase II trials. Thirty-six patients had metastatic melanoma, 35 had metastatic renal cell cancer, and 22 had colorectal cancer. All patients had a Karnofsky performance status greater than or equal to 80% and normal laboratory tests and organ function, and had received no more than one prior form of immunotherapy or chemotherapy. Objective responders were eligible to receive up to two additional courses of therapy at 12-week intervals. The most frequent toxicities were a capillary leak syndrome resulting in marked extravascular fluid shifts, and hypotension requiring treatment with large volumes of IV fluids and vasopressor agents. Laboratory and clinical evidence of hepatic and renal dysfunction were virtually universal. Intensive care-level support was routinely provided and the toxicity observations confirmed the need for this level of care. The life-threatening toxicities were cardiac and pulmonary. Five of the 27 patients who experienced significant respiratory compromise required intubation and mechanical ventilatory support. Twenty patients developed cardiac arrhythmias, the majority of which were supraventricular. There was a single episode of ventricular tachycardia requiring cardioversion. Four patients had transient cardiac ischemia, and an additional four had myocardial infarctions, one of which was fatal. With these exceptions, all toxicities were rapidly reversible. The occurrence of only a single therapy-related death and a very low incidence of other irreversible or life-threatening events is comparable to the level of toxicities often observed in other phase II trials. Although the intensity of this regimen limits this approach to a subset of cancer patients with excellent performance status and adequate organ function, because of the frequency and apparent durability of complete responses, this treatment warrants further investigation.

Vaccination of renal cell cancer (RCC) patients with modified vaccinia Ankara (MVA) delivering tumor antigen 5T4 administered alone or with interleukin 2 (IL-2) or interferon-alpha (IFN)

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 3026-3026
Author(s):  
R. Amato ◽  
J. Hernandez-McClain ◽  
R. Harrop ◽  
P. Cen ◽  
G. Doshi
Keyword(s):  
Overall Survival ◽  
Specific Antibody ◽  
Tumor Antigen ◽  
Karnofsky Performance Status ◽  
Performance Status ◽  
Cell Cancer ◽  
Single Agent ◽  
Interleukin 2 ◽  
Magnetic Resonance Imaging Scan ◽  
Serious Adverse Events

3026 Background: The attenuated vaccinia virus (MVA) has been engineered to deliver the tumor antigen 5T4 (TroVax). More than 90% of RCCs overexpress the 5T4 antigen. A series of clinical trials were conducted to evaluate the effectiveness of MVA 5T4 as a single agent or in combination with either IL-2 or IFN. Methods: Eligibility: Pathologic diagnosis of clear cell or papillary RCC, progressive measurable metastases, any prior therapy, adequate physiological parameters, Karnofsky performance status ≥ 80%, and no active CNS involvement. A regimen of MVA 5T4 alone or in combination with IL-2 or IFN was given. Results: A total of 53 pts received MVA 5T4 alone or in combination with IL-2 or IFN. 13 pts received MVA 5T4 alone, 25 pts received low dose subcutaneous IL-2, and 15 pts received IFN. Clinical responses were assessed by measuring changes in tumor burden via computed tomography or magnetic resonance imaging scan. 5T4-specific cellular and humoral responses were monitored throughout the study. 5T4 was well tolerated with no serious adverse events attributed to vaccination. Of 48 intention-to-treat pts, 43 mounted 5T4-specific antibody responses. 2 pts showed a complete response for > 36 months and 2 other pts had a partial response for > 24 months and 12 months respectively. 20 pts demonstrated disease stabilization for ≥ 3 months. Median progression-free survival and overall survival for all pts was 3.6 months (range 0.8–29.7) and 13.2 months (range 1–38) respectively. A significant relationship was detected between the magnitude of 5T4-specific antibody response and overall survival. Conclusions: 5T4, whether administered alone or in combination, was well tolerated. High frequency of 5T4-specific immune responses and associated enhanced patient survival is encouraging and warrants further investigation. [Table: see text]

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