Clinical Oncology

Development of malignant ascites is common in patients with ovarian cancer, and few therapeutic options exist for women with ascites whose tumors become resistant to chemotherapy. Furthermore, in such patients symptom palliation options are limited, and the few available treatments are unpleasant and can result

To determine tumor-related factors that influence the response of metastatic melanoma tumors to treatment with the anti-CTLA-4 antibody ipilimumab, researchers have performed gene-profiling assays on biopsies collected from 45 patients before and after treatment with ipilimumab. In patients who responded to treatment, expression of immune-related

An interesting therapy combination has been uncovered in preclinical studies. In an ovarian cancer cell line, the proteasome inhibitor bortezomib acted synergistically with indole-3-carbinol, a natural compound found in cruciferous vegetables. Treatment with the combination induced cell-cycle arrest and apoptosis and sensitized the cells to

A large population study has been completed in Sweden that aimed to identify whether there is a familial link for acute myeloid leukemia (AKL) and myelodysplastic syndromes (MDS). Interestingly, having a first-degree relative with AML or MDS did not increase the risk of developing either

A recent phase II trial has shown that bevacizumab is tolerated by patients with nasopharyngeal carcinoma. The trial assessed patients with grade IIB–IVB disease and combined treatment with bevacizumab and cisplatin with intensity-modulated radiation therapy. There were no grade 5 adverse events, which was one

Harbeck, N. Nat. Rev. Clin. Oncol.9, 10–12 (2012); doi:10.1038/nrclinonc.2011.193In the version of this article initially published online the author's name in the citation line was spelled incorrectly. The error has been corrected for the

B-cell chronic lymphocytic leukemia (CLL) is the most common type of leukemia and it is characterized by the accumulation of impaired mature B lymphocytes in the blood and bone marrow. Although it progresses slowly in many cases and these patients may have normal active lives

Peritoneal carcinomatosis resulting from metastatic colorectal cancer (pcCRC) is a relatively common and under recognized condition with a very poor prognosis. The presentation of pcCRC is distinct from hepatic or pulmonary metastases yet most studies do not differentiate CRC subtypes. The lack of a widely

Before the advent of HER2-targeted therapies, the 20–25% of patients with breast tumors that overexpressed HER2 had a poor prognosis. The approval and use of the HER2-targeted monoclonal antibody trastuzumab has gone some way to ameliorating this problem; however, more treatment options are still needed.

Despite the fact that up to 10% of colorectal cancers (CRC) have mutations in the Val600 codon of BRAF, the clinical response to treatment with the V600E B-Raf targeted agent vemurafenib has not been encouraging. Researchers based at Roche (the developing company of vemurafenib)

Glioblastoma multiforme (GBM) is the most common and aggressive brain tumor in adults, and it is very difficult to treat as it is resistant to most conventional therapies, probably due to its heterogeneous nature. Tumorigenesis of GBM is commonly driven by gene amplification of tyrosine

Androgen-deprivation therapy (ADT) is widely used for the treatment of patients with prostate cancer, but has been suggested to increase a patient's risk of dying from cardiovascular complications. However, in a meta-analysis of eight prospective, randomized trials with over 4,000 patients, a team of researchers

Highly clinically relevant ovarian cancer clinical research in 2011 focused on an increased understanding of the biology of the malignancy, limitations of strategies for early detection and screening, and the provocative reports of alternative primary and second-line management strategies.

Options to treat late-stage castration-resistant prostate cancer continued to increase in 2011, as three agents with different mechanisms of action prolonged life and a fourth reduced the morbidity of skeletal metastases. These outcomes contrasted with the heightened controversy generated by the recommendation against PSA screening and other early detection strategies.

2011 saw improvements in our understanding of B-cell malignancies: insights into the genomic basis of chronic lymphocytic leukemia were achieved; reduced treatment intensity caused fewer toxic effects in early-stage Hodgkin lymphoma; first-line rituximab maintenance therapy improved outcome in follicular lymphoma; and selected patients with diffuse large-cell lymphoma benefited from the addition of bortezomib.

Melanoma has emerged as the paradigm tumor for drug development through mutation-targeted therapies (inhibitors targeting BRAF, MEK, and c-KIT) and immunotherapy. Exploring the combinations of both approaches is a challenge that will require scientific rationale and the cooperation of the pharmaceutical industry. But, with these challenges comes another opportunity to change the paradigms in drug development.

Bone-targeting treatments have transformed the quality of life of patients with metastatic bone disease. 2011 saw the emergence of denosumab—a RANK ligand-specific antibody—as a more-effective alternative treatment to bisphosphonates and of data on the use of bone-targeting treatments to prevent metastasis from breast and prostate cancers.

Metastases in the central nervous system (CNS) are identified in up to 30% of patients at autopsy. Rates of CNS involvement in metastatic cancer are believed to be increasing, possibly owing to better control of systemic disease with novel chemotherapies or improved metastasis detection. The

Despite the development of drugs inhibiting the oncogenic proteins that cancer cells are dependent on, attempts to match targeted therapies to the genetic makeup of individual tumors is proving more difficult than expected. Until now, the paradigm has been a binary correlation between a mutated

The advent of targeted anticancer therapies over the past few decades has reinvigorated the field of cancer therapeutics, with the promise of increased cancer cure rates accompanied by decreased toxicity. But, has that promise been fulfilled? The short answer is definitely 'no', both because of

Elucidation of the molecular pathways underlying bone turnover has revealed potential therapeutic targets, including receptor activator of nuclear factor-κB ligand (RANKL), which is a mediator of osteoclast formation, function and survival. Denosumab is a fully human monoclonal antibody that binds to and inhibits RANKL. This

In 2009, the Union for International Cancer Control issued the seventh edition of the well-used T (tumor), N (node), and M (metastasis) classification guidelines. There has been a continual refinement of the staging for colorectal cancer since this system for assessing tumor stage was initially

Hematological cancer: A new option for patients with PTCL Nature Reviews Clinical Oncology. doi:10.1038/nrclinonc.2012.11 Author: Rebecca Kirk

Lung cancer: How to switch on a tumor suppressor Nature Reviews Clinical Oncology. doi:10.1038/nrclinonc.2012.18

Head and neck cancer: Salivary biomarkers for early detection of oral cancer Nature Reviews Clinical Oncology. doi:10.1038/nrclinonc.2012.20

Head and neck cancer: Good old acupuncture Nature Reviews Clinical Oncology. doi:10.1038/nrclinonc.2012.19

Despite advances in treating multiple myeloma with the proteasome inhibitor bortezomib and the immunomodulatory drugs thalidomide and lenalidomide, most patients eventually relapse. In this Review, the authors discuss how next-generation inhibitors and immunotherapy agents have been developed based on an improved understanding of the biology of the disease, and highlight the challenges associated with these therapeutic approaches.

In terms of drug development, the main driving force should be optimized benefit–risk to patients; however, no drug can be of real benefit unless it has achieved approval from the regulatory agencies. This Perspectives allows us a peek behind the door of one of those agencies (EMA) and outlines the hurdles that exist and that need to be overcome before we can have an efficient, biomarker-driven drug development program. Points for discussion in the community are raised and suggestions are put forward.

Urological cancer: Are we redeemed from aggressive treatment for prostate cancer? Nature Reviews Clinical Oncology. doi:10.1038/nrclinonc.2012.10 Author: M. Teresa Villanueva

Clinical trials have consistently demonstrated the superior sensitivity of human papillomavirus (HPV) testing compared with cytology (Pap) testing for identifying women at risk of cervical cancer. Rijkaart et al. have now shown that adding HPV testing to routine cervical cancer screening can further reduce the risk of cervical cancer compared to Pap testing alone.

The BOLERO-2 and CLEOPATRA trials evaluated everolimus for estrogen receptor-positive and pertuzumab for HER2-positive metastatic breast cancer. Both agents enhanced the efficacy of standard therapy, were relatively well tolerated and should be approved for therapeutic use. These data confirm that targeting both major driver and escape pathways improves treatment outcomes.

Should dynamic contrast-enhanced (DCE)-MRI be used in the assessment of drug-development of antivascular agents? In this Review, O'connor et al. discuss whether data from DCE-MRI are reliable and reproducible biomarkers of drug efficacy, and whether they assist in dose selection and drug scheduling in the design of early clinical trials.

DNA repair as a therapeutic target has received considerable attention in the treatment of non-small-cell lung cancer (NSCLC). In this Review, Postel-Vinay et al. discuss how optimizing treatment of NSCLC according to DNA-repair biomarkers, such as ERCC1, BRCA1 or RRM1, may aid clinical decision making and improve the outcome of patients with NSCLC.

Antiangiogenic therapies have secured a role in the treatment of multiple cancers. However, the success of this targeted therapy is not as great as originally anticipated. In this Perspectives article, the authors use data from clinical trials to uncover where some of the problems with this therapy lie, discuss exciting recently published data and look to what the next steps should be.

Breast cancer: Anastrozole sets the STAGE for premenopausal women Nature Reviews Clinical Oncology. doi:10.1038/nrclinonc.2012.13 Author: Lisa Hutchinson

Lung cancer: Practical assay to predict survival Nature Reviews Clinical Oncology. doi:10.1038/nrclinonc.2012.17 Author: Lisa Hutchinson

Gynecological cancer: DOvE pilots its way to intriguing results Nature Reviews Clinical Oncology. doi:10.1038/nrclinonc.2012.12 Author: Rebecca Kirk

Targeted therapies: Smart tumor, smarter treatment Nature Reviews Clinical Oncology. doi:10.1038/nrclinonc.2012.4 Author: M. Teresa Villanueva

Late toxicities from radiation therapy are frequent in patients with Hodgkin lymphoma and can hamper survival. These late toxicities should decrease with modern radiation therapy but results are not mature and so the importance of this decrease is still unknown. Hence, all studies in Hodgkin lymphoma must report long-term outcome.

The increasing reliance on hazard ratios for the assessment of clinical trial data prompted this Perspectives article, designed to outline the uses and misuses of this popular statistical value. The authors use real trial data and synthetic examples to explain how the hazard ratio is derived and why the numerical value of a survival measure should also be published alongside it.

Urological cancer: TKIs strike back: complete remission in kidney cancer Nature Reviews Clinical Oncology. doi:10.1038/nrclinonc.2012.5 Author: Lisa Hutchinson

Urological cancer: Cause and effect in prostate cancer Nature Reviews Clinical Oncology. doi:10.1038/nrclinonc.2012.6 Author: Rebecca Kirk

Patients with cancer who also have hepatitis B virus (HBV) or hepatitis C virus (HCV) infection have a significant morbidity and mortality. HBV reactivation is a serious but preventable complication of immunosuppressive therapy. The authors discuss the epidemiology, pathogenesis, risk factors, and clinical and laboratory manifestations associated with the reactivation of HBV and HCV during immunosuppressive therapy, and discuss strategies for the prevention and treatment of viral reactivation.

Randomized controlled trials (RCTs) pose dilemmas in terms of the tension between the therapeutic obligations of the physician and the scientific obligations of the investigator. Clinical equipoise is often regarded as a solution to this problem. The authors critically evaluate clinical equipoise and highlight its flaws as an ethical requirement for RCTs and propose an alternative method of risk–benefit assessment.

If a targeted therapy demonstrates convincing efficacy in early clinical testing, can randomized phase III trials be avoided? Sharma and Schilsky discuss when it is reasonable to consider foregoing randomized phase III trials before drug approval and also highlight the caveats. They explore the consequences of such an approach and propose criteria that the drugs must meet to be approved without a phase III trial.

The size, length and cost of phase III clinical trials are prompting oncology researchers and pharmaceutical companies to look for other options. This Review outlines adaptive clinical trial designs that can address many questions at once. A wholly new paradigm for drug development exemplifying personalized medicine is evinced by an adaptive trial called I-SPY2, in which drugs from many companies are evaluated in the same study and are matched with their biomarker signatures