Reviews & Analysis

Erythropoiesis-stimulating agents are widely used in patients with cancer; however, uncertainty persists over their effect on survival. This article discusses the results of a meta-analysis of randomized, controlled trials of these agents in patients with cancer.

This case study discusses two patients with locally advanced Merkel cell carcinoma. The authors describe how neoadjuvant polychemotherapy was used to treat these patients allowing curative-intent surgery plus radiotherapy.

The costs associated with innovative cancer therapeutics are excessive, placing a barrier between drug discovery and healthcare. The article discusses several strategies that might be effective in reducing the escalating costs and their impact on innovative cancer drug discovery.

With the development of new chemotherapy and targeted agents, neurotoxicity has become increasingly important as a cause of dose-limiting toxicity. The authors review the important and unusual neurotoxicities related to chemotherapy and targeted agents approved since January 1999.

With greater understanding of the biology of pancreatic cancer a role for cancer stem cells is becoming clear. The authors of this Review discuss the current knowledge on pancreatic cancer stem cells and their potential use as targets in therapeutic regimens.

Imatinib is the standard frontline therapy for patients with chronic myeloid leukemia (CML); however, a substantial number require alternative therapy owing to imatinib intolerance or imatinib resistance. Studies have shown that second-generation tyrosine kinase inhibitors are efficacious in restoring cytogenetic responses in patients who require subsequent therapy. Quintás-Cardama et al. discuss the second-generation and third-generation targeted agents that have restored cytogenetic response in patients unresponsive to imatinib, and the strategies being explored to improve the long-term outcome.

Imatinib is known to be effective in the first-line treatment of metastatic gastrointestinal stromal tumors. A randomized, placebo-controlled trial has now shown that imatinib is safe and improves recurrence-free survival when used as adjuvant therapy after surgical resection of a primary gastrointestinal stromal tumor.

Patients with extensive small-cell lung cancer who are treated with prophylactic cranial irradiation experience fewer brain metastases and prolonged survival compared with their counterparts. Slotman and colleagues have presented a detailed analysis of the effects of prophylactic cranial irradiation on health-related quality of life in these patients.

The incidence of tonsillar cancer in the UK has doubled over the past decade and the discovery of the human papillomavirus in tonsillar cancer specimens has been hypothesized to be the cause. We discuss and propose an explanation of how a reduction in tonsillectomy rates may be responsible for this increase in tonsillar cancer.

Central nervous system prophylaxis is recommended with the administration of high-dose methotrexate and/or intrathecal injection of chemotherapy in patients with anaplastic large-cell lymphoma (ALCL). Researchers investigated whether methotrexate dose, infusion duration and intrathecal mode of administration had an impact on the risk of systemic and central nervous system relapses in children with ALCL.

Lasting complete remission from widespread bone metastases is rare. The case of a 41-year-old premenopausal woman diagnosed with right-sided infiltrating ductal breast carcinoma andBRCA2mutation is described. She received high-dose anthracycline-based induction chemotherapy followed by autologous bone marrow transplantation with high-dose alkylator and platin-based conditioning regimens. The authors comment on the reasons for this unusual and sustained complete remission from widely metastatic breast cancer and the patient-specific factors that may have contributed to this outcome.

Bevacizumab has improved survival outcomes in patients with various solid tumors when combined with chemotherapy. The authors discuss the rationale for using bevacizumab and other large-molecule agents that target the VEGF system, and the unanswered questions regarding the use of bevacizumab in the adjuvant setting. The challenges and opportunities in developing new strategies and understanding molecular mechanisms are highlighted.

Cetuximab and panitumumab have been approved for the treatment of metastatic colorectal cancer when used alone or in combination with irinotecan. Although EGFR is expressed in most metastatic colorectal tumors, only a subset of patients derive clinical benefit from treatment with EGFR inhibitors. The experimental and clinical evidence supporting the use ofKRAStesting for selecting patients for treatment with anti-EGFR monoclonal antibodies is discussed.

KRASmutations can be predictive of resistance to anti-EGFR monoclonal-based therapy in patients with colorectal cancer. Only limited studies, however, have assessed the predictive value ofKRAS mutations in response to conventional chemotherapy. In this Review, the authors assess the available literature and propose that KRASmutations have no value in response prediction to conventional chemotherapy in colorectal cancer, non-small-cell cancer and other solid tumors.

Dynamics of cells reactions and behavior between cells can be integrated into models of cancer using systems pathology. Integrating multiple data from the clinic to make models sufficiently robust to be of practical use is a challenge. The difficulties in using mathematics to model cancer are highlighted, and some approaches in systems biology and experimental pathology that may be applied successfully in the clinic are discussed.

Antiangiogenic agents that target the VEGF pathway have become an important part of standard therapy in multiple cancer indications. Although most adverse effects of VEGF inhibitors are modest and manageable, some are associated with serious and life-threatening consequences. This Review examines the toxicity profiles of anti-VEGF monoclonal antibodies and small-molecule inhibitors and considers the potential mechanisms of the adverse effects, risk factors, and the implications for patient management.

Brain metastases are a challenge for the oncologist, with 20–40% of cancer patients developing intracranial metastases during the course of their illness. The incidence of brain metastases is increasing as a result of improvements in systemic therapy and imaging capabilities, and increased use of screening. Brain metastases pose not only a risk to mortality but also a risk of neurologic, cognitive and emotional difficulties.

The role of laparoscopic resection for rectal cancer is currently unclear, with little supportive evidence from randomized trials. A study by Ng et al. in a large series of patients with rectal cancer has shown that laparoscopic resection is safe with good long-term outcomes.

Pelvic lymphadenectomy offers no therapeutic benefit to women diagnosed with early-stage endometrial cancer according to a new study. Lymphadenectomy can only be recommended as part of a clinical trial in this disease setting; however, it can offer valuable staging information in those with advanced disease.

The first-line treatment for patients with unresectable metastatic colorectal cancer is chemotherapy in combination with bevacizumab. Emerging evidence, however, suggests that the addition of cetuximab—an anti-EGFR monoclonal antibody—to chemotherapy might be beneficial to patients with wild-type KRAS tumors.