Volume 7 Issue 2, February 2010

Activating mutations in EGFR are characteristic of patients with lung cancer who have high sensitivity to EGFR tyrosine kinase inhibitors, such as gefitinib and erlotinib. The randomized IPASS study by Mok and colleagues confirmed that patients with EGFR mutations have a higher response rate, longer progression-free survival and improved quality of life when treated with first-line gefinitib instead of chemotherapy.

Currently, acquisition of tissue from presumed metastatic deposits in breast cancer is not routine. Instead therapeutic decisions in this setting are based on the features of the tumor at initial diagnosis. As biopsies are diagnostic and changes can occur between the primary and the secondary tumors, the routine biopsy of suspected metastatic deposits needs to be considered. Such biopsies will also be key to translational research, which will underpin future therapeutic advances.

We reviewed the results of the Gynecological Oncology Group 204 (GOG-204) randomized phase III trial, which investigated four cisplatin combination chemotherapy regimens for the treatment of patients with recurrent or metastatic cervical carcinoma. As the overall survival was similar between all arms, treatment recommendations need to be tailored based on toxic effects.

The considerable progress made in the field of clinical neuro-oncology and the understanding of brain tumor biology is generating cautious optimism. Treatment options for patients with glioblastoma multiforme (GBM), the most common form of malignant gliomas, now include anti-angiogenic therapy after failure of standard multi-modality treatments. Furthermore, scientific advancements are providing new insights into disease pathogenesis and point to novel therapeutic approaches for a disease that traditionally lacked treatment options.

Chemotherapy options for patients with extensive-stage small-cell lung cancer (SCLC) are limited. A recent phase III trial assessed the combination of carboplatin and pemetrexed but this regimen produced inferior survival results compared with the standard carboplatin and etoposide regimen. The combination of carboplatin and etoposide remains the standard first-line chemotherapy option for the treatment of patients with extensive-stage SCLC.

Dose-dense chemotherapy has been proposed to improve breast cancer outcome due to its ability to prevent cancer cell repopulation; however, little is known about which patients benefit most from such scheduling. A pooled analysis of studies assessing dose-dense adjuvant chemotherapy has shown that most of the therapeutic benefit derived from dose-dense scheduling arises in patients with node-positive, triple-negative disease.

First-line platinum and taxane chemotherapy improves the prognosis of patients with epithelial ovarian cancer (EOC), however, about 80% of patients relapse and long-term survival is poor. The development of drug resistance is the main cause of treatment failure; therefore, the identification of new compounds that interfere with tumor growth and survival is a priority.

Members of the nuclear receptor superfamily of transcription factors have been implicated in a broad range of normal physiological and disease processes. There is evidence in support of the involvement of these co-regulators in breast cancer progression. The authors review the role of steroid receptor coactivator-3, which is frequently amplified in breast cancer, and discuss its role in breast cancer risk, outcome and response to endocrine therapy in patients with breast cancer.

There has been extensive research evaluating the clinical usefulness of genomic biomarkers. High-throughput genomic technologies have revolutionized genomic research but challenges in biomarker assessment include clinical study design, reproducibility and interpretation of results. This Review explores these challenges, focusing on microarray-based gene-expression profiling, and highlights some common failings in study design that have impacted on the clinical use of putative genomic markers.

Trastuzumab and lapatinib improve survival in patients with HER2-positive breast cancer and there is great interest in developing diagnostic tests that predict which patients are more likely to benefit from specific HER2-directed therapies. This article discusses the predictive role ofHER2mRNA, predictive markers for response to therapy and the mechanisms for overcoming resistance in metastatic disease.

It has been established that intraperitoneal drug administration is advantageous in patients with tumors confined to the peritoneal cavity. The authors of this Review discuss intraperitoneal drug delivery including the optimal drug, dose and schedule.

A 71-year-old male patient was diagnosed with aKIT-positive gastrointestinal stromal tumor (GIST). The patient received adjuvant imatinib but developed several subcutaneous and intra-abdominal tumor lesions after 4 months of treatment. A T-cell lymphoproliferative disorder was suspected. The authors discuss the potential of imatinib to induce reversible clonal T-cell proliferations in patients with GIST who develop new tumor manifestations that are suspicious for relapse.