Reviews & Analysis

Rini and colleagues provide additional data on bevacizumab and interferon-α in clear-cell carcinoma of the kidney; a comparison of these results with the findings from contemporary trials suggests that bevacizumab and interferon-α is another clinically useful treatment option for patients with metastatic renal-cell carcinoma.

Preclinical studies have shown that new agents such as bortezomib not only demonstrate anti-multiple-myeloma activity as single agents but also enhance the efficacy of both chemotherapy and steroids. A randomized trial has established that bortezomib not only improves response rates but also prolongs the lives of patients with multiple myeloma who are not candidates for high-dose chemotherapy.

The disappointing results of the large, randomized, controlled trials showing no benefit of vaccines in patients with advanced and metastatic melanoma call for a reassessment of the development of therapeutic vaccines and the importance of better immune monitoring methodology, such as adoptive T-cell therapy with lymphodepletion.

In the movement towards individualized treatment regimens, Rothenberg et al. validate XELOX as another available systemic therapy for patients being treated with second-line treatment for metastatic colorectal cancer. This paper adds to a growing body of data in the first-line and second-line setting that confirms the noninferiority of oral fluoropyrimidine-containing regimens.

A prospective subgroup analysis of two prospective, randomized, double-blind, placebo-controlled phase III clinical trials showed that the combination of lenalidomide plus dexamethasone is superior to dexamethasone alone in patients with relapsed or refractory multiple myeloma who had been previously treated with thalidomide; the implications for clinical practice are discussed.

The EICESS-92 trial compared the efficacy of cyclophosphamide and ifosfamide in patients with Ewing sarcoma. Subgroup analysis suggested that patients with large, localized tumors benefited from the addition of etoposide, whereas patients with metastases did not.

MSH2mutations are associated with the development of colorectal cancer and are a common cause of Lynch syndrome. Jeans et al. describe the case of a 37-year-old woman with a germline MSH2mutation who developed rectal adenocarcinoma and 7 years later presented with a primitive neuroectodermal tumor. The authors suggest that diagnosis of Lynch syndrome should be considered in cases where individuals with previous malignancies associated with this syndrome present with cerebral tumors.

The development of novel molecularly targeted agents requires a re-evaluation of the current drug development paradigm. Gutierrez et al. discuss the opportunities and challenges facing drug development in the oncology field, such as optimum clinical trial design, patient selection, optimal biologic dose versus maximum tolerated dose, and definition of response criteria and suitable endpoints for clinical trials.

The recently reported results of the IPASS trial showed superior progression-free survival for gefitinib compared with carboplatin and paclitaxel chemotherapy as first-line treatment in Asian patients with non-small-cell lung cancer who were non-smokers and had adenocarcinoma histology. Saijo et al. examine the reasons for the differences in the effects of molecular-targeted drugs and cytotoxic antineoplastic agents observed in this trial and other studies, and consider how this could affect future clinical trial design and analysis.

Endoscopic ultrasound and endobronchial ultrasound are new tools for the mediastinal staging of non-small-cell lung cancer. These techniques allow minimally invasive and accurate sampling of mediastinal lymph nodes. Navani et al. discuss the current methods available for mediastinal lymph-node staging, focusing on endoscopic and endobronchial ultrasound. The authors present a new diagnostic algorithm incorporating these techniques for the intra-thoracic staging of non-small-cell lung cancer.

A number of clinical studies have demonstrated that patients with high-risk squamous-cell carcinoma of the head and neck benefit from the addition of EGFR inhibitors to chemotherapy and radiotherapy. The rationale for using targeted therapies based on inhibition of EGFR and angiogenesis, and the most recent pre–clinical and clinical evidence for the role of these agents in the management of head and neck cancers is discussed.

The molecular characterization of disseminated tumor cells and circulating tumor cells opens a new avenue for understanding cancer dormancy and might contribute to the identification of metastatic stem cells with important implications for future therapies. This Review focuses on the clinical relevance of the latest research results on blood-borne cancer micrometastasis in patients with cancer.

The findings from a multicenter, screening trial of CT colonography for the detection of large adenomas demonstrated the benefit of this noninvasive technique for assessing patients with an average risk of colorectal cancer.

Patients with a immunohistochemically defined, germinal-center tumor subtype have an improved outcome compared with patients with the non-germinal-center phenotype when treated with CHOP only, according to a prospective study. The benefit was not observed in those treated with the rituximab combination therapy.

Zoledronic acid is effective in the prevention of bone loss in premenopausal women with breast cancer being treated with endocrine therapy. The benefit of zoledronic acid probably extends for some years after cessation of therapy.

Substantial progress has been made in radical cystectomy in the past 25 years, and development of orthotopic lower urinary tract reconstruction has been an important step in the continued progress of urinary diversion. The orthotopic neobladder should be considered the gold standard with which other forms of diversion are compared.

Resistance to chemotherapy remains one of the major challenges in the treatment of patients with multiple myeloma. Chim et al. report the case of a 59-year-old woman with multiple myeloma, who progressed after treatment with conventional chemotherapeutic agents. Addition of bortezomib to her treatment regimen resulted in complete regression of her disease. The authors suggest that bortezomib can restore chemosensitivity of myeloma cells in heavily pretreated, chemorefractory patients with multiple myeloma.

Transurethral resection of the bladder and adjuvant chemoradiation can permit eradication of the tumor and micrometastases. Close monitoring by sequential cystoscopy and biopsy can achieve similar survival outcomes to radical cystectomy, and could avoid invasive treatment.

Comparison of circulating tumor cell numbers before and after treatment is predictive for overall survival in patients with metastatic castration-resistant prostate cancer; this comparison is more helpful than prostate-specific antigen detection, according to a recent study.

Most brain tumors secrete high levels of vascular endothelial growth factor, which can lead to an abnormally permeable tumor vasculature. This hyperpermeability causes vasogenic cerebral edema and increased interstitial fluid pressure, which can prevent adequate penetration of chemotherapy agents to the tumor. This Review focuses on the pathophysiology of vasogenic edema and the potential utility of agents that target angiogenesis, and particularly the vascular endothelial growth factor pathway.