Reviews & Analysis

There is extensive in vitro and in vivo preclinical evidence that bisphosphonates, particularly zoledronic acid and ibandronate, have antitumor activity, can reduce skeletal tumor burden, and might potentially have antitumor activity outside the bone microenviroment. The authors of this review highlight the importance of correct sequencing of these compounds when used in conjunction with cytotoxic drugs, targeted molecular therapies, and radiotherapy. The need to identify new molecular targets of nitrogen-containing bisphosphonates is discussed in this context and the correct sequence and the timing of drug administration could help drive molecular research and determine the efficacy of the therapy, both in advanced disease and in the adjuvant setting.

No single indicator provides unambiguous information regarding the population burden and dynamics of breast cancer. Milena Sant and co-authors discuss the trends in incidence, survival and mortality for patients with breast cancer in Western Europe and suggest a strategy for analysis of these data.

Several randomized trials have demonstrated improved survival rates and local control when concurrent cisplatin-based chemotherapy was added to radiation therapy in patients with locoregionally advanced cervical cancer. Randomized trials that investigated the administration of neoadjuvant chemotherapy before radiation therapy, however, have failed to demonstrate a benefit of this approach. Based on clinical trial evidence cisplatin-based chemoradiation should be considered a standard treatment for most patients with locoregionally advanced carcinoma of the cervix who do not have medical contraindications to this aggressive treatment.

Despite the impressive results seen in phase II trials of trastuzumab, many tumors that overexpress HER2 show resistance to the drug. Understanding the molecular mechanisms underlying primary or treatment-induced trastuzumab resistance is critical to improving the survival of patients with metastatic breast cancer with aggressive HER2 overexpressing tumors. This review discusses the novel therapeutic strategies that target the aberrant molecular pathways, and explains how these strategies could greatly improve the duration of response to trastuzumab.

Proteomics can help to define and identify patients that will most benefit from the increasing number of molecular-targeted agents. In particular, reverse phase protein microarray provides detailed information about the state of the cellular 'circuitry' from small samples such as patient biopsy specimens. This review discusses the clinical applications of this emerging technology and how it could be used to help guide individualized treatment approaches.

Although the epidermal growth factor receptor tyrosine kinase inhibitors gefitinib and erlotinib can produce dramatic and durable tumor responses, not all patients with non-small-cell lung cancer (NSCLC) benefit from these drugs. This Viewpoint discusses the molecular correlates of response for these agents in patients with NSCLC.

For the treatment of advanced non-small-cell lung cancer, randomized controlled trials have shown that platinum-based chemotherapy and radiotherapy provide a measurable survival benefit compared with radiotherapy alone. Newer drugs that target growth factor receptors might further synergize with ionizing irradiation, although convincing data from multicenter phase III are currently lacking. The authors discuss why concurrent chemoradiation followed by consolidation platinum-based chemotherapy is an attractive approach for treating patients with inoperable tumors.

Recent advances in tumor cytogenetics and molecular biology have clarified that renal-cell carcinoma is not a single entity but comprises a variety of tumors with different histological features, genetic patterns and varying clinical course. Since many cancer molecular markers have been described, this information could help to discriminate aggressive tumors from indolent lesions. The authors describe the benefits of predictive nomograms for improving risk assessment, and discuss the prospects for individual customized follow-up protocols based on tumor molecular characteristics.

The use of central venous catheters (CVC) has improved the management of patients with cancer but this procedure is associated with complications such as infections and upper limb deep-vein thrombosis. This review describes the epidemiology of CVC-related thrombosis and the risk factors associated with this problem. The authors comment on the diagnosis and presentation of CVC-related thrombosis and consider how cancer patients with this complication can be appropriately managed with long-term anticoagulant therapy.

When is chemotherapy too well tolerated? This Viewpoint discusses the possibilities that some patients receive inadequate doses of chemotherapy using the conventional dose calculation method based on body surface area and that a correlation between hematological toxicity and treatment efficacy could be used to titrate therapy.

The myoepithelial cell exerts profound effects on breast tumor cell behavior and resides close to abnormally proliferating breast epithelial cells in precancerous ductal carcinomain situ(DCIS) tumors. These cells also form a natural border separating breast epithelial cells from stromal angiogenesis. Barsky and Karlin discuss the role myoepithelial cells may have in inhibiting the progression of DCIS to invasive breast cancer, and the functional studies that are elucidating the anti-invasive and anti-angiogenic phenotypes of these cells.

Anemia can be a debilitating problem that negatively influences overall quality of life, and it can worsen the prognosis for cancer patients. The requirement for red-blood cell transfusions is reduced in patients receiving erythropoietin therapy. This review discusses quality of life issues, the thromboembolic complications associated with erythropoietin treatment, and provides a critical appraisal of the clinical trial data and evidence-based guidelines for erythropoietin treatment.

Glioblastoma multiforme (GMB) is a devastating neoplasm that nearly always culminates in death within 1–2 years of diagnosis. Despite decades of intensive clinical and laboratory research, progress has been slow, partly because of limited drug delivery and tumor heterogeneity. David Reardon describes an innovative chemoradiation approach that has improved overall survival for newly diagnosed GBM patients, and details a number of promising therapeutic strategies under evaluation.

The Investigational New Drug (IND) process was established to ensure that the FDA is informed of any new treatment before use in humans. The process is now used for approval rather than notification. The time from conception to approval for a new drug is estimated at over 15 years, of which two-thirds is devoted to pre-IND testing. In the meantime the patient is denied access to the investigational treatment. A centralized IND procedure, when the public are already protected by processes within academic centers of excellence, is redundant and costs lives.

Cancer mortality is highest in cancer patients aged 65 years or older. Optimal chemotherapy dosing and regimens for these patients pose a significant challenge because of changes that occur with aging, as well as other comorbidities. This review discusses the important considerations for tailoring chemotherapy to the individual's performance and functional status.