clinicaltrials.gov Identifier: NCT01279967.

Background No phase 3 trial has yet shown improved survival for patients with pleural or peritoneal malignant mesothelioma who have progressed following platinum-based chemotherapy. The aim of this study was to assess the efficacy and safety of nivolumab, an anti-PD-1 antibody, in these patients.Methods This was a multicentre, placebo-controlled, double-blind, parallel group, randomised, phase 3 trial done in 24 hospitals in the UK. Adult patients (aged ≥18 years) with an Eastern Cooperative Oncology Group performance status of 0 or 1, with histologically confirmed pleural or peritoneal mesothelioma, who had received previous first-line platinum-based chemotherapy and had radiological evidence of disease progression, were randomly assigned (2:1) to receive nivolumab at a flat dose of 240 mg every 2 weeks over 30 min intravenously or placebo until disease progression or a maximum of 12 months. The randomisation sequence was generated within an interactive web response system (Alea); patients were stratified according to epithelioid versus non-epithelioid histology and were assigned in random block sizes of 3 and 6. Participants and treating clinicians were masked to group allocation. The co-primary endpoints were investigator-assessed progression-free survival and overall survival, analysed according to the treatment policy estimand (an equivalent of the intention-to-treat principle). All patients who were randomly assigned were included in the safety population, reported according to group allocation. This trial is registered with Clinicaltrials.gov, NCT03063450.

This is the first study to identify stage and tumor markers as prognostic parameters for patients with MOGCTs. This might help to select patients for risk-adapted treatment. There is need for improvement of therapeutic strategies after relapse.

Purpose: There is a need for new treatments for Hodgkin and T-cell lymphoma due to the development of drug resistance in a proportion of patients. This phase I study of radioimmunotherapy used CHT-25, a chimeric antibody to the α-chain of the interleukin-2 receptor, CD25, conjugated to iodine-131 ( 131 I) in patients with refractory CD25-positive lymphomas. Experimental Design: Fifteen patients were treated (Hodgkin lymphoma, 12; angioimmunoblastic T-cell lymphoma, 1; adult T-cell leukemia/lymphoma, 2). Tumor was monitored by computed tomography and in all but two patients by 18 F-fluorodeoxyglucose positron emission tomography. Results: There were no grade 3 or 4 infusion reactions. At the maximum tolerated dose of 1,200 MBq/m 2 , the major side effect was delayed myelotoxicity with the nadir for platelets at 38 days and for neutrophils at 53 days. One patient treated with 2,960 MBq/m 2 developed prolonged grade 4 neutropenia and thrombocytopenia and died of Pneumocystis jiroveci pneumonia. Nonhematologic toxicity was mild. Single photon emission computer tomography imaging showed tumor-specific uptake and retention of In spite of recent advances in therapy, there remains an acute need for improved treatments for Hodgkin lymphoma (HL) and other lymphomas. For instance, there is only a 50% prospect of long-term disease free survival for patients with relapsed HL responding to high-dose chemotherapy and autologous stem cell transplant (1, 2). The interleukin-2 (IL-2) receptor is selectively overexpressed in HL and other lymphomas and therefore is a potential target for new therapies. Radioimmunotherapy (RIT) with 131 I)-labeled chimeric antibody to the IL-2 receptor (CD25)] has been developed for this purpose and a phase I study in relapsed HL and T-cell lymphoma is reported.CD25 is a 55-kDa 3 protein with three transmembrane protein chains that is induced on T-cell activation but is not found on B or T lymphocytes or monocytes in the resting state (3, 4). Hodgkin/Reed-Sternberg cells frequently express CD25, and the

Purpose: In preclinical models, radioimmunotherapy with 131 I-A5B7 anti^carcinoembryonic antigen (CEA) antibody ( 131 I-A5B7) combined with the vascular disruptive agent combretastatin-A4-phosphate (CA4P) produced cures unlike either agent alone. We conducted a phase I trial determining the dose-limiting toxicity (DLT), maximum tolerated dose, efficacy, and mechanism of this combination in patients with gastrointestinal adenocarcinomas. Experimental Design: Patients had CEA of 10 to 1,000 Ag/L, QTc V450 ms, no cardiac arrhythmia/ischaemia, and adequate hematology/biochemistry.Tumor was suitable for blood flow analysis by dynamic contrast enhanced-magnetic resonance imaging (MRI).

Angiogenesis is an essential process in the development and growth of tumours.

The management of androgen independent prostate cancer is increasingly disputed. Diethylstilbestrol and steroids have useful second-line activity in its management. The value of chemotherapy still remains contentious. This paper reports a phase 2 study of two orally active chemotherapy drugs in patients who are absolutely hormone refractory having failed primary androgen blockade and combined oestrogens and corticosteroids. In total, 37 patients who were biochemically castrate with absolute hormone refractory prostate cancer and performance status of 0 -3 were enrolled. Therapy consisted of chlorambucil 1 mg kg À1 given as 6 mg a day until the total dose was reached and lomustine 2 mg kg À1 given every 56 days (CL56). During this time all hormone therapy was stopped. One patient normalised his PSA with a further two having a greater than 50% decline leading to an objective response rate of 10%. The median time to progression was 3.6 months with an overall survival of 7.1 months. The median survival of this group of patients from first becoming androgen independent was 23.5 months. Eight of 17 (47%) patients who were subsequently rechallenged with hormonal therapy following failure of chemotherapy had a further PSA reduction, three (17%) of which were 450%. The median progression-free interval for the eight patients was 4 months. In conclusion, CL56 has a low objective response rate in the management of absolute hormone refractory prostate cancer. Toxicity was mild. Re-induction of hormone sensitivity following failure of chemotherapy was an unexpected finding that requires further study.

We review the current status of imaging as applied to targeted therapy with particular focus on antibody-based therapeutics. Antibodies have high tumor specificity and can be engineered to optimize delivery to, and retention within, the tumor. Whole antibodies can activate natural immune effector mechanisms and can be conjugated to beta- and alpha-emitting radionuclides, toxins, enzymes, and nanoparticles for enhanced therapeutic effect. Imaging is central to the development of these agents and is used for patient selection, performing dosimetry and assessment of response. gamma- and positron-emitting radionuclides may be used to image the distribution of antibody-targeted therapeutics While some radionuclides such as iodine-131 emit both beta and gamma radiation and are therefore suitable for both imaging and therapy, others are more suited to imaging or therapy alone. Hence for radionuclide therapy of neuroendocrine tumors, patients can be selected for therapy on the basis of gamma-emitting indium-111-octreotide imaging and treated with beta-emitting yttrium-90-octreotate. Positron-emitting radionuclides can give greater sensitivity that gamma-emitters but only a single radionuclide can be imaged at one time and the range of radionuclides is more limited. The multiple options for antibody-based therapeutic molecules, imaging technologies and therapeutic scenarios mean that very large amounts of diverse data are being acquired. This can be most effectively shared and progress accelerated by use of common data standards for imaging, biological, and clinical data.