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.

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

scholarly journals Predictors of Response to Targeted Therapy in Renal Cell Carcinoma

2012 ◽  
Vol 136 (5) ◽  
pp. 490-495 ◽  
Author(s):  
Laurie J. Eisengart ◽  
Gary R. MacVicar ◽  
Ximing J. Yang
Keyword(s):  
Renal Cell Carcinoma ◽  
Targeted Therapy ◽  
Cell Carcinoma ◽  
Targeted Therapies ◽  
Renal Cell ◽  
Mammalian Target Of Rapamycin ◽  
Interleukin 2 ◽  
High Dose ◽  
Predictors Of Response ◽  
Personalized Approach

Context.—The prognosis for patients with metastatic renal cell carcinoma is poor, with an average 5-year survival of approximately 10%. Use of traditional cytokine therapy, specifically high-dose interleukin 2, is limited by significant toxicity. Better understanding of the molecular pathogenesis of renal cell carcinoma has led to the development of targeted therapies to inhibit specific cellular pathways leading to tumorigenesis. These drugs provide improved survival with a more favorable toxicity profile. There is ongoing investigation of markers that predict response of an individual patient to different targeted therapies. Objective.—To explain the molecular basis for vascular endothelial growth factor inhibitor (antiangiogenic) and mammalian target of rapamycin inhibitor therapies for renal cell carcinoma, summarize the clinical trials demonstrating the effectiveness of these drugs, and describe the biomarkers shown to correlate with outcome in patients treated with targeted therapy. Data Sources.—All included sources are from peer-reviewed journals in PubMed (US National Library of Medicine). Conclusion.—Emerging evidence shows promise that biomarkers will be useful for predicting an individual patient's response to targeted therapy, leading to a more personalized approach to treating renal cell carcinoma.

How Did We Obtain Complete Remission in Patients Who Had Metastatic Renal Cancer in the Era of Targeted Therapies?

2016 ◽  
Vol 24 (2) ◽  
pp. 369-374 ◽  
Author(s):  
François Brécheteau ◽  
Souhil Lebdai ◽  
Julie Carrouget ◽  
Jérôme Lebigot ◽  
Cosmina Nedelcu ◽  
...  
Keyword(s):  
Complete Remission ◽  
Renal Cancer ◽  
Targeted Therapies ◽  
Metastatic Renal Cancer

Subcutaneous interleukin-2 plus interferon alfa-2a in metastatic renal cancer: an outpatient multicenter trial.

1993 ◽  
Vol 11 (9) ◽  
pp. 1809-1816 ◽  
Author(s):  
N J Vogelzang ◽  
A Lipton ◽  
R A Figlin
Keyword(s):  
Complete Remission ◽  
Median Survival ◽  
Renal Cancer ◽  
Low Dose ◽  
Interleukin 2 ◽  
Interferon Alfa ◽  
Phase Iii ◽  
Survival Duration ◽  
Metastatic Renal Cancer ◽  
Median Survival Duration

PURPOSE A prospective multicenter phase II trial was undertaken to define the activity of a low-dose subcutaneous regimen of interleukin-2 (IL-2) and interferon alfa-2a (IFN) in patients with metastatic renal cancer. PATIENTS AND METHODS Between December 1990 and October 1991, 42 patients with metastatic renal cancer who had received no prior immunotherapy were treated with IL-2 (4 x 10(6) U) days 1 through 4 and IFN (9 x 10(6) U) day 1 and 4 each week of a 4-week treatment course followed by a 2-week rest period. Maximum duration of therapy was 1 year. Concomitant therapy with acetaminophen, diphenhydramine, and indomethacin was recommended. Treatment was administered on an outpatient basis. RESULTS With a median follow-up duration of 18 months, responses occurred in five of 42 patients (12%; 95% confidence interval [Cl], 2% to 22%). One pathologic complete remission, one surgical complete remission, and three partial remissions occurred. Toxicity was modest, with a symptom complex of rash, fever, anorexia, fatigue, mild weight loss, lymphocytosis, and eosinophilia occurring in 85% to 90% of patients. Renal dysfunction (creatinine > 2 mg/dL) occurred in 19% of patients, while three patients (7%) refused further IL-2 and IFN. No toxic deaths occurred. The median survival duration was 14.5 months. CONCLUSION This outpatient low-dose subcutaneous regimen induced mild toxicity, a modest response rate, and an excellent median survival duration in previously untreated patients. Phase III trials are now needed to compare IL-2 plus IFN with IL-2 alone or to various IL-2/IFN regimens. However, the major task is to identify unique new agents with activity in renal cancer.

531 How did we obtain complete remission with patients who have metastatic renal cancer using targeted therapies?

2016 ◽  
Vol 15 (3) ◽  
pp. e531 ◽  
Author(s):  
F. Brecheteau ◽  
J. Carrouget ◽  
S. Lebdai ◽  
A.R. Azzouzi ◽  
P. Bigot
Keyword(s):  
Complete Remission ◽  
Renal Cancer ◽  
Targeted Therapies ◽  
Metastatic Renal Cancer

scholarly journals High-Dose Chemotherapy with Bendamustin and Melphalan Improves the Rate of Complete Remission in Myeloma Patients in First Remission Compared to Standard Melphalan Alone

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 39-40
Author(s):  
Sarah Farag ◽  
Ulrike Bacher ◽  
Myriam Legros ◽  
Daniel Betticher ◽  
Jean-Marc Lüthi ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Flow Cytometry ◽  
Complete Remission ◽  
Median Time ◽  
Maintenance Treatment ◽  
Induction Treatment ◽  
High Dose ◽  
First Line ◽  
Term Survival ◽  
Pulmonary Failure

Introduction: Consolidation of first-line induction treatment in myeloma (MM) patients (pts) with 200 mg/m2 melphalan chemotherapy (HDCT) and autologous stem cell transplantation (ASCT) was established as standard of care three decades ago. However, definite cure in myeloma patients remains exceptional due to residual disease escaping intensive treatment, and almost all patients will ultimately relapse at earlier or later time points following ASCT. Thus, improving efficacy of HDCT in MM remains an unresolved issue. Methods: We performed a phase-II randomized trial comparing standard 200 mg/m2 Melphalan (Mel) HDCT to experimental HDCT treatment with 200 mg/m2 bendamustine, a bifunctional alkylating agent, given at days -4 and -3, combined with 200 mg/m2 melphalan split on days -2 and -1 at 100 mg/m2 (BenMel) before ASCT in MM pts. Patients had up to four cycles of first-line induction treatment with bortezomib, lenalidomide and dexamethasone. After ASCT, pts received lenalidomide maintenance treatment for two years. The primary endpoint was to show a 15% improvement of the rate of complete remission (sCR+CR) after HDCT with BenMel compared to Mel alone. MRD assessment from the bone marrow was performed by multiparameter flow cytometry after hematological engraftment following HDCT/ASCT. MRD negativity was defined as clonal plasma cells below 10(-5). Results: We randomized 120 myeloma pts (60 patients in each arm), with high-risk genetic abnormalities present in 21.3% of the patients. The median age was 63 years (range 35-74). The sCR/CR rate after ASCT before initiation of lenalidomide maintenance treatment was better in the BenMel arm compared to Mel alone (70.0% vs 51.7%; p=.039). The post-ASCT remission rates in detail were sCR 40.0% vs 31.7% (p=.341); CR 30.0% vs 20.0% (p=.205); VGPR 16.7% vs 33.3% (p=.035); and PR 13.3% vs 15.0% (p=.793). MRD negativity assessed in the bone marrow by flow cytometry was observed in 26 (45.6%) of the BenMel treated pts compared to 22 (37.9%) of the Mel pts. Median time until neutrophil engraftment was 11 days after BenMel vs 12 days after Mel (p=.096), and median time until platelet engraftment was 13 days in both arms (p=0.367); all pts had full engraftment of both cell lineages. Prolonged hospitalization duration was seen in BenMel pts (median 19 vs 18 days; p=.006) due to the longer BenMel treatment administration. Fully reversible acute renal insufficiency occurred in three (5%) BenMel pts compared to none of the Mel pts (p=.250). No treatment-related mortality was seen in both groups. ICU admissions were necessary in 3 pts (5%) in the BenMel group (ARDS, septic shock, pulmonary failure), and 2 Mel treated pts (3.3%; due to pulmonary failure and decompensated cardiomyopathy). The PFS rates at 12 months were 95% in BenMel pts and 91% in Mel treated pts (p=.551). OS at 12 months was 96% for both groups (p=.262), and median PFS and OS were not reached in both groups. Conclusions: Our data confirm that high-dose bendamustine combined with melphalan HDCT before ASCT in MM patients is safe and well tolerated. In particular, bendamustine-associated renal toxicity was manageable and reversible in all patients, and hematopoietic engraftment was comparable to standard melphalan HDCT. HDCT with BenMel improves the sCR/CR rate compared to standard melphalan alone. Thus, BenMel HDCT before ASCT warrants further investigation aiming to improve the long-term survival rates of MM patients, eventually combined with new maintenance strategies in the post-transplant period. Figure 1 Disclosures No relevant conflicts of interest to declare.

Outcome of patients with Hodgkin's disease failing after primary MOPP-ABVD.

1997 ◽  
Vol 15 (2) ◽  
pp. 528-534 ◽  
Author(s):  
V Bonfante ◽  
A Santoro ◽  
S Viviani ◽  
L Devizzi ◽  
M Balzarotti ◽  
...  
Keyword(s):  
Prognostic Factors ◽  
Complete Remission ◽  
Hodgkin's Disease ◽  
Hodgkin’S Disease ◽  
Response Duration ◽  
Long Term Results ◽  
High Dose ◽  
First Line ◽  
Disease Extent

PURPOSE This study analyzed long-term results in patients with Hodgkin's disease who were resistant to or relapsed after first-line treatment with MOPP and ABVD. Response to salvage treatments and prognostic factors were also evaluated. PATIENTS AND METHODS The study population included 115 refractory or relapsed patients among a total of 415 patients treated with alternating or hybrid MOPP-ABVD followed by radiotherapy (25 to 30 Gy) to initial bulky sites. The median follow-up duration of the present series was 91 months. Thirty-nine of 115 patients (34%) showed disease progression while on primary treatment (induction failures); 48 relapsed after complete remissions that lasted < or = 12 months and 28 after complete remission that lasted more than 12 months from the end of all treatments. RESULTS At 8 years, the overall survival rate was 27%, being 54% and 28% in patients whose initial complete remission was longer or shorter than 12 months, respectively, and 8% in induction failures (P < .001). Response to first-line chemotherapy and disease extent at first progression significantly influenced long-term results, as well as the incidence and duration of complete remission. CONCLUSION The present data confirm previous observations that showed the main prognostic factors to influence outcome after salvage treatment are response duration to first-line therapy and disease extent at relapse. The results indicate that patients who relapse after the alternating MOPP/ABVD regimen have a prognosis similar to that of patients who relapse after a four-drug regimen (MOPP or ABVD alone). Re-treatment with initial chemotherapy seems the treatment of choice for patients who relapse after an initial complete remission that lasts greater than 12 months, while the real impact of high-dose chemotherapy or new regimens should be assessed in resistant patients.

scholarly journals High-dose cytosine arabinoside and mitoxantrone: a highly effective regimen in refractory acute myeloid leukemia

Blood ◽  
1987 ◽  
Vol 69 (3) ◽  
pp. 744-749 ◽  
Author(s):  
W Hiddemann ◽  
H Kreutzmann ◽  
K Straif ◽  
WD Ludwig ◽  
R Mertelsmann ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Complete Remission ◽  
Cytosine Arabinoside ◽  
Myeloid Leukemia ◽  
High Dose ◽  
Antileukemic Activity ◽  
First Line ◽  
Clinical Phase ◽  
Refractory Acute Myeloid Leukemia ◽  
Acute Myeloid

Abstract In a clinical phase I/II study, high-dose cytosine arabinoside and mitoxantrone (HAM) were given in combination to 40 patients with refractory acute myeloid leukemia. All patients had received a 9-day combination of thioguanine, Ara-C, and daunorubicin (TAD-9) as standardized first-line treatment. Refractoriness was defined as (a) nonresponse against two TAD-9 induction cycles, (b) early relapse within the first 6 months on monthly maintenance or after TAD-9 consolidation, (c) relapse after 6 months with nonresponse against one additional TAD-9 cycle, and (d) second and subsequent relapses after successful TAD-9 therapy at the preceding relapse. Therapy consisted of HD-Ara-C 3 g/m2 every 12 hours on days 1 through 4; mitoxantrone was started at 12 mg/m2/day on days 3, 4, and 5 and was escalated to 4 and 5 doses of 10 mg/m2/day on days 2 through 5 and 2 through 6. Of the 40 patients, 21 achieved a complete remission (53%), 1 patient had a partial remission, and 5 patients were nonresponders. Thirteen patients died in aplasia due to infections (n = 11), pericardiac effusion, or acute cardiomyopathy. Nonhematologic side effects consisted predominantly of nausea and vomiting, mucositis, and diarrhea. Central nervous system (CNS) symptoms were observed during six treatment courses. Recovery of blood counts occurred at a median of 27 days from the onset of treatment; the median time to complete remission was 36 days. Two of the 21 responders underwent successful bone marrow transplantations. The median remission duration for the remaining 19 patients is 4.5 months, and the median survival time is 9 months. These data emphasize that HAM has high antileukemic activity in refractory AML and strongly suggest starting the combination at earlier stages in AML therapy.

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