Volume 11 Issue 9, September 2014

Cytotoxic agents are conventionally dosed on the basis of the maximum tolerated dose defined in phase I trials. A study assessing adverse events in over 2,000 patients treated with molecularly targeted agents suggests a need to redefine criteria for dosing of molecularly targeted agents, which should be based on randomized, dose-ranging phase II trials.

The PREVAIL trial compared enzalutamide and placebo in patients with metastatic castration-resistant prostate cancer who had not received prior chemotherapy, demonstrating an improvement in overall survival and other clinical, radiographic, and biochemical outcomes. Herein, the implications of these data in the rapidly changing landscape of metastatic prostate cancer therapy are discussed.

Hepatocellular carcinoma is a difficult-to-treat cancer and, after numerous phase III trials assessing kinase inhibitors have failed to meet their end points, sorafenib is the only accepted treatment for advanced stages of the disease. Now, the trial EVOLVE-1 has shown a lack of benefit for everolimus in the second-line treatment setting.

Active immunotherapy is emerging as an important addition to conventional cancer treatments, but many important questions remain. Optimal combinations of antigens, adjuvants and delivery vehicles need to be determined and effective strategies for overcoming tumour-associated immunosuppression ought to be developed. This Review provides an overview of new results from clinical studies of therapeutic cancer vaccines directed against tumour-associated antigens and discusses their implications for the use of active immunotherapy.

The treatment options available for hepatocellular carcinoma (HCC) vary depending on prognostic factors that include tumour characteristics and clinical status, particularly with regard to liver function. This Review discusses the links between disease phenotype, prognosis and therapy, focusing on the subclassification of patients with intermediate-stage HCC following the BCLC staging system, who are usually ineligible for curative resection and ablation treatments or liver transplantation; the therapies that are available for this patient subgroup are described.

Graft-versus-host disease (GVHD) is the most serious and challenging complication of allogeneic haematopoietic stem-cell transplantation (HSCT). There is a need for developing new approaches to mitigate GVHD and ultimately facilitate the use of allogeneic HSCT for the treatment of haematological cancers. In this Review, the authors discuss rationale, clinical evidence, and outcomes of the current GVHD prophylaxis and assess the clinical evidence for emerging approaches in the prevention of GVHD.

Patients with oligometastases who develop a small number of metastatic lesions might achieve long-term survival with the use of ablative surgery or stereotactic radiotherapy. More patients are receiving aggressive treatment for oligometastatic disease, yet long-term survival might not be due to the treatments themselves, but rather to the selection of patients with slow-growing indolent disease. The authors examine the key evidence supporting or refuting the existence of an oligometastatic state and its appropriate treatment.