Reviews & Analysis

The results from two large, prospective, randomized, controlled trials examining the role of 5-α reductase inhibitors in the prevention of prostate cancer have been published. Initial results from the Prostate Cancer Prevention Trial (PCPT) were met with both enthusiasm and skepticism. The recently published REDUCE trial seems to corroborate the findings of the PCPT and reinforce the chemopreventive potential of 5-α reductase inhibitors. This article will assess the REDUCE trial and place the results of the 5-α reductase inhibitor trials in the context of clinical practice.

Nanoparticles are a promising vector-based strategy for the therapeutic administration of small interfering (si)RNA because they protect siRNA from nuclease degradation. A recent phase I study employed transferrin–targeted nanovectors to demonstrate RNA interference mechanisms in a melanoma patient. Multifunctional nanoparticles are providing patient-specific biodistributions of systemically administered siRNA.

A 63-year-old woman with chronic myeloid leukemia who achieved a complete cytogenic response after 6 years of interferon-alpha went on to lose molecular response 2 years after treatment cessation. In this Case Study, Monica Bocchia and colleagues demonstrate the positive outcome in this patient following treatment with a therapeutic vaccine that consists of the p210 BCR–ABL1-derived peptide. The patient has maintained a complete molecular response for over 39 months.

Radiotherapy has an important role in the treatment of metastatic epidural spinal cord compression; when used alone, it is important to select the most suitable radiotherapy regimen. In this Review, Rades and Abrahm report that longer-course radiotherapy is associated with better local control than short-course radiotherapy. However, short-course radiotherapy is more suitable than longer-course treatment in patients with a poor prognosis.

Adjuvant treatment with anthracycline–taxane combination therapy in high-risk early-stage breast cancer has raised the important question of how to manage patients who relapse. In the metastatic setting, one option is rechallenging with the same agent, or class of agent, that has been used in the adjuvant setting. This Review comprehensively examines the evidence from clinical trials for rechallenging with both anthracyclines and taxanes, and highlights issues to be examined in the context of future clinical trials.

Bone is the most common site of breast cancer metastasis, resulting in substantial morbidity and mortality. A number of therapies are being developed, including bisphosphonates, which target factors that promote tumor growth in bone. The authors of this Review outline the underlying mechanisms that drive this pathological process, and highlight potential molecular targets that will improve therapeutic interventions for metastatic breast cancer. Tools that assess response in individual patients and guide appropriate treatment are also discussed.

Cancer treatment in young women can lead to reduced fertility—a serious issue for patients who wish to have children. In this Perspectives, Letourneau and coauthors highlight the importance of making sure that oncologists and fertility teams are aware of this issue and work together to educate patients of the risks involved. Furthermore, options for fertility preservation are discussed.

This Review focuses on the adverse effects of radical radiotherapy for localized prostate cancer. The authors discuss the methodological issues that make comparison between the different treatment modalities problematic, and describe the pattern of adverse effects that occur over time after radiotherapy. Recent technical advances, such as intensity modulation and image guidance, will hopefully further improve the toxicity profile of prostate radiotherapy.

Two seemingly contradictory methods of practicing medicine, evidence-based medicine and personalized medicine are examined with respect to PET imaging in this Perspective. The improvement that PET imaging provides for patient management in both hematologic and solid malignancies is discussed. The tailoring of therapeutic strategy by molecular imaging, with PET at its forefront, enables disease management at the individual level and strengthens the evidence-based approach in oncology.

Inhibitors of poly(ADP-ribose)polymerase (PARP) have shown promise as therapeutic agents for the treatment of ovarian cancers with mutations inBRCA1 or BRCA2. By exploiting the synthetic lethal interaction that exists between PARP inhibition and BRCA mutations, these agents specifically kill cancer cells by targeting their DNA repair system. The authors of this Review describe the importance of BRCAmutations for the efficacy of PARP inhibitors. They also discuss the preclinical and clinical trial results of PARP inhibitors, the challenges related to the use of these agents, and future directions.

Antiangiogenic therapy inhibits tumor growth by targeting the blood vessels of the tumor. Antiangiogenic therapy often correlates with longer survival in patients without affecting tumor growth. This positive response may be due to the off-tumor target effects of antiangiogenic drugs. In this article, Yihai Cao describes the potential mechanisms underlying the benefits of targeting off-tumor sites, and how these events improve outcomes in patients with cancer-associated systemic syndromes.

This Review discusses the advantages and disadvantages of weekly paclitaxel for the treatment of relapsed ovarian cancer. When compared with the 3 weekly schedule, weekly paclitaxel is better tolerated, with a reduced frequency of toxic effects; however, response duration can be short. Importantly, patients with tumors that are resistant to 3-weekly paclitaxel have responded to treatment with weekly paclitaxel. Current research focuses to increase response duration include the combination of weekly paclitaxel with molecular-targeted agents and the use of molecular profiling to better select patients for treatment.

Ongoing investigation into the use of thalidomide in the treatment of multiple myeloma has demonstrated efficacy as a combination treatment during induction and as maintenance therapy. Thalidomide–doxorubicin–dexamethasone combination therapy improved response rate; however, the development of drug resistance remains a concern.

The optimum approach for the treatment of rare anaplastic gliomas following surgical resection is uncertain. A recent study has now provided a greater understanding of the heterogeneous tumor biology of these tumors and has emphasized the prognostic importance of chromosome 1p19q deletion, IDH mutation and MGMT promoter methylation. The importance of radiotherapy and chemotherapy for treating these heterogeneous tumors is being elucidated for subgroups of patients.

Investigators found that denileukin diftitox, which targets the interleukin-2 receptor, achieves objective response rates in 44% of patients with cutaneous T-cell lymphoma, with a median duration of response of 7.8 months and 2% incidence of severe vascular leak syndrome. The inclusion of a placebo arm in the study revealed several additional interesting observations.

A phase III trial investigated the efficacy of carboplatin and a taxane with and without cetuximab, a monoclonal antibody against EGFR, in patients with advanced non-small-cell lung cancer. This trial did not reveal an improvement in the primary end point of progression-free survival (according to an independent radiological review committee) with the addition of cetuximab to the carboplatin and taxane regimen. A retrospective investigation of potential biomarkers did not reveal any significant association between these biomarkers and cetuximab efficacy.

Brain metastases are a frequent complication in patients with advanced breast cancer. Whole-brain radiation therapy (WBRT) is the standard treatment for these patients, but it can cause neurocognitive damage, and results are suboptimal. Therapies that reduce toxic effects, improve local control, and prevent recurrences are needed. The authors of this Review outline the current strategies and novel developments in WBRT, and discuss new irradiation modalities that are improving outcomes in breast cancer patients with brain metastases.

Modern cancer treatment is a complex process that requires the cooperation of individuals with a range of specialties and backgrounds. In this Perspective, a multidisciplinary team of authors propose a conceptual model to improve patient-centered cancer care. This model describes the roles of the active caregivers (for example, physicians), basic supportive caregivers (for example, psychologists) and community support (for example, advocacy groups) in providing the full continuum of the cancer treatment experience.

Chronic lymphocytic leukemia has long been regarded as an incurable disease of the elderly. Consolidation strategies using non-cross resistant agents have improved the success rates of patients with residual disease at the end of induction treatment. This Review discusses chemoimmunotherapy regimens that contain purine analogs and rituximab and considers new developments in induction and consolidation strategies that are leading the path towards cure.

Castleman's disease is an infectious disease of the lymph node that causes either local symptoms or a systemic inflammatory syndrome. This Review discusses the viral causes of the disease and the mechanisms of its subsequent progression. The efficacy of established treatment options for this disease and of potential novel therapies is outlined.