6 research outputs found
Adoptive Immunotherapy with Interleukin-2 and Interferon-alpha in Metastatic Renal Cell Cancer
Approximately one half of all newly diagnosed cancer patients will die of
metastatic disease despite the application of the best available treatment consisting
of surgery, radiation therapy and chemotherapy. Attempts to develop new approaches
for the treatment of metastatic cancer by stimulating immune host defences
against the tumor have received substantial attention. Initially most efforts to
develop immunotherapies have involved nonspecific stimulation of the immune
system with unspecific immunostimulants such as Bacille Calmette Guerin or
Corynebacterium parvum. However, clinical trials have been disappointing and this
immunotherapeutic approach has been abandoned. An alternative approach is that
of adoptive immunotherapy, which is defined as the transfer of immunologic
reagents or immune cells with antitumor reactivity to the tumor bearing host
Intrapleural administration of tumour necrosis factor alpha (TNFα) in patients with mesothelioma: Cytokine patterns and acute-phase protein response
Vemurafenib plus cobimetinib in unresectable stage IIIc or stage IV melanoma
Background: In patients with BRAFV600 mutated unresectable stage IIIc or metastatic melanoma, molecular targeted therapy with combined BRAF/MEK-inhibitor vemurafenib plus cobimetinib has shown a significantly improved progression-free survival and overall survival compared to treatment with vemurafenib alone. Nevertheless, the majority of BRAFV600 mutation-positive melanoma patients will eventually develop resistance to treatment. Molecular imaging with 18F-Fluorodeoxyglucose (18F-FDG) PET has been used to monitor response to vemurafenib in some BRAFV600 mutated metastatic melanoma patients, showing a rapid decline of 18F-FDG uptake within 2 weeks following treatment. Furthermore, preliminary results suggest that metabolic alterations might predict the development of resistance to treatment. 18F-Fluoro-3'-deoxy-3'L-fluorothymidine (18F-FLT), a PET-tracer visualizing proliferation, might be more suitable to predict response or resistance to therapy than 18F-FDG. Methods: This phase II, open-label, multicenter study evaluates whether metabolic response to treatment with vemurafenib plus cobimetinib in the first 7 weeks as assessed by 18F-FDG/18F-FLT PET can predict progression-free survival and whether early changes in 18F-FDG/18F-FLT can be used for early detection of treatment response compared to standard response assessment with RECISTv1.1 ceCT at 7 weeks. Ninety patients with BRAFV600E/K mutated unresectable stage IIIc/IV melanoma will be included. Prior to and during treatment all patients will undergo 18F-FDG PET/CT and in 25 patients additional 18F-FLT PET/CT is performed. Histopathological tumor characterization is assessed in a subset of 40 patients to unravel mechanisms of resistance. Furthermore, in all patients, blood samples are taken for pharmacokinetic analysis of vemurafenib/cobimetinib. Outcomes are correlated with PET/CT-imaging and therapy response.
Metastatic uveal melanoma: Treatment strategies and survival—results from the dutch melanoma treatment registry
Uveal melanoma (UM) is the most common primary intraocular tumor in adults. Up to 50% of UM patients will develop metastases. We present data of 175 metastatic UM patients diagnosed in the Netherlands between July 2012 and March 2018. In our cohort, elevated lactate dehydrogenase level (LDH) is an important factor associated with poorer survival (Hazard Ratio (HR) 9.0, 95% Confidence Interval (CI) 5.63–14.35), and the presence of liver metastases is negatively associated with survival (HR 2.09, 95%CI 1.07–4.08). We used data from the nation-wide Dutch Melanoma Treatment Registry (DMTR) providing a complete overview of the location of metastases at time of stage IV disease. In 154 (88%) patients, the liver was affected, and only 3 patients were reported to have brain metastases. In 63 (36%) patients, mutation analysis was performed, showing a GNA11 mutation in 28.6% and a GNAQ mutation in 49.2% of the analyzed patients. In the absence of standard care of treatment options, metastatic UM patients are often directed to clinical trials. Patients participating in clinical trials are often subject to selection and usually do not represent the entire metastatic UM population. By using our nation-wide cohort, we are able to describe real-life treatment choices made in metastatic UM patients and 1-year surv
Repeated administrations of interleukin (IL)-12 are associated with persistently elevated plasma levels of IL-10 and declining IFN-gamma, tumor necrosis factor-alpha, IL-6, and IL-8 responses
PURPOSE: Repeated administrations of recombinant human interleukin-12
(rHuIL-12) to cancer patients are characterized by a reduction of side
effects during treatment. Induction of IFN-gamma, considered a key
mediator of antitumor effects of IL-12, is known to decline on repeated
administrations. We studied whether other immunological effects of
rHuIL-12 are tapered in the course of treatment. EXPERIMENTAL DESIGN: In a
Phase I study of 26 patients with advanced renal cell cancer, rHuIL-12 was
administered s.c. on day 1, followed by 7 days rest and six injections
administered over a 2-week time period. Plasma concentrations of various
cytokines were monitored, as well as absolute counts of circulating
leukocyte and lymphocyte subsets. RESULTS: The first injection of IL-12
was accompanied by rapid, transient, and dose-dependent increments of
plasma levels IFN-gamma, tumor necrosis factor-alpha, IL-10, IL-6, IL-8,
but not IL-4, as well as rapid, transient, and dose-dependent reductions
of lymphocyte, monocyte, and neutrop
High-dose regimen of interleukin-2 and interferon-alpha in combination with lymphokine-activated killer cells in patients with metastatic renal cell cancer
Seventy-two patients with metastatic renal cell cancer were treated with the combination of high-dose interleukin-2 (IL2), interferon-alpha (IFNa), and lymphokine-ac