Phase I study to determine the safety, tolerability and immunostimulatory activity of thalidomide analogue CC-5013 in patients with metastatic malignant melanoma and other advanced cancers

We assessed the safety, tolerability and efficacy of the immunomodulatory drug, CC-5013 (REVIMID(TM)), in the treatment of patients with metastatic malignant melanoma and other advanced cancers. A total of 20 heavily pretreated patients received a dose-escalating regimen of oral CC-5013. Maximal tolerated dose, toxicity and clinical responses were evaluated and analysis of peripheral T-cell surface markers and serum for cytokines and proangiogenic factors were performed. CC-5013 was well tolerated. In all, 87% of adverse effects were classified as grade 1 or grade 2 according to Common Toxicity Criteria and there were no serious adverse events attributable to CC-5013 treatment. Six patients failed to complete the study, three because of disease progression, two withdrew consent and one was entered inappropriately and withdrawn from the study. The remaining 14 patients completed treatment without dose reduction, with one patient achieving partial remission. Evidence of T-cell activation was indicated by significantly increased serum levels of sIL-2 receptor, granulocyte- macrophage colony-stimulating factor, interleukin-12 (IL-12), tumour necrosis factor-alpha and IL-8 in nine patients from whom serum was available. However, levels of proangiogenic factors vascular endothelial growth factor and basic foetal growth factor were not consistently affected, This study demonstrates the safety, tolerability and suggests the clinical activity of CC-5013 in the treatment of refractory malignant melanoma. Furthermore, this is the first report demonstrating T-cell stimulatory activity of this class of compound in patients with advanced cancer

Successful treatment of multiple myeloma relapsing after high-dose therapy and autologous transplantation with thalidomide as a single agent

A 52-year-old dentist with kappa light chain multiple myeloma relapsed 6 months after 180 mg/m(2) melphalan and an autograft. A partial remission had been attained after the autograft. Relapse occurred while he was on dexamethasone maintenance therapy. Chemotherapy was not an option due to low blood counts. Thalidomide was administered at relatively high doses (escalated up to 700 mg daily and continued for 4 months). There was a prompt decline in urine protein from 6067 mg/day to 2177 mg/day within a month. The response continued to improve with achievement of near-complete remission within 6 months and a decline in urine protein to 413 mg/day. Subsequently, grade 3 neutropenia and peripheral neuropathy required dose reduction to 200 mg/day, Disease activity parameters continued to improve on the lower dose of thalidomide. Nine months after starting thalidomide, the patient is in near-complete remission, enjoys an excellent quality of life, and has returned to work. We conclude that thalidomide can effectively control myeloma relapsing after high-dose chemotherapy, and may be especially useful in resistant cases or those unable to tolerate further chemotherapy

Successful treatment of multiple myeloma relapsing after high-dose therapy and autologous transplantation with thalidomide as a single agent

A 52-year-old dentist with kappa light chain multiple myeloma relapsed 6 months after 180 mg/m(2) melphalan and an autograft. A partial remission had been attained after the autograft. Relapse occurred while he was on dexamethasone maintenance therapy. Chemotherapy was not an option due to low blood counts. Thalidomide was administered at relatively high doses (escalated up to 700 mg daily and continued for 4 months). There was a prompt decline in urine protein from 6067 mg/day to 2177 mg/day within a month. The response continued to improve with achievement of near-complete remission within 6 months and a decline in urine protein to 413 mg/day. Subsequently, grade 3 neutropenia and peripheral neuropathy required dose reduction to 200 mg/day, Disease activity parameters continued to improve on the lower dose of thalidomide. Nine months after starting thalidomide, the patient is in near-complete remission, enjoys an excellent quality of life, and has returned to work. We conclude that thalidomide can effectively control myeloma relapsing after high-dose chemotherapy, and may be especially useful in resistant cases or those unable to tolerate further chemotherapy

Urban pocket - reclaiming the public in leftover open spaces - a methodological guide

Urbego believes that neglected public spaces can be transformed into key places where the city beats on the rhythm of the community and neighbourhood activism. Together with local institutional partners and residents, we have undertaken a series of actions in 2014 that address the role and function of public space. So far, Urbego has sparked interest in the re-establishment of public space as a relevant arena in Belgrade, Tirana and Skopje, mapping, surveying, gaming, creating and working with citizens on their visions of what public space ought to be. The experiment was successful, marked by the implementation of a community pocket park in the Albanian capital in January 2015

Predictive factors for response to rituximab in Waldenstrom's macroglobulinemia

Rituximab is an active agent for the treatment of Waldenstrom’s macroglobulinemia. However, many patients do not respond to this agent and several others develop secondary resistance. In order to identify clinical and laboratory parameters that could predict a higher likelihood for response, we evaluated 54 patients who were treated with single-agent rituximab. Twenty-four patients (44%)exhibited >= 50% reduction of serum monoclonal protein. Previously untreated and pretreated patients had the same probability for response. Low response rates were noted in patients with serum monoclonal protein level >= 40 g/L (17%) and serum albumin level < 35 g/L (14%). Furthermore, a multivariate analysis indicated that high serum monoclonal protein and low albumin were the dominant variables associated with shorter time to progression. The presence of 2, 1, or none of these variables was associated with median times to progression of 4 months, 11 months, and approximately 48 months, respectively. We conclude that patients with low levels of monoclonal protein and normal albumin are the best candidates for treatment with rituximab