Volume 2 Issue 11, November 2005

This Viewpoint assesses whether prostate cancer screening within the US is justifiable outside clinical trials. Prostate-specific antigen (PSA) values may fluctuate for physiologic reasons and the natural history of the disease varies between individuals. PSA testing increasingly identifies too many cases of indolent disease that would never have threatened patients' lives.

The evidence for prostate cancer screening using prostate-specific antigen with reference to UK criteria is presented. Such screening might result in considerable over-diagnosis and over-treatment of clinically insignificant prostate cancer. Morbidity associated with treatment of suspected prostate cancer is substantial, so the likelihood of harm may outweigh the prospect of benefit.

The identification of somatic mutations in the epidermal growth factor receptor (EGFR) gene and promising clinical trial data showing a favorable clinical response to associated gefitinib and erlotinib in non-small-cell lung cancer patients was a major breakthrough in the field. Should patient selection for treatment with these drugs, however, be solely based on mutational EGFR status? Giaccone and Rodriguez discuss ways in which mutational analysis could be optimized, highlight factors that might help define sensitivity to EGFR inhibitors, and comment on how to select those patients who would benefit from treatment.

Based on preclinical data, it has been suggested that antiangiogenic compounds could improve cytotoxic drug delivery because of their effects on tumor endothelium. Most of the early clinical testing of these agents was conducted in patients with advanced disease resistant to standard therapies, and while some of the phase III trial data were disappointing, recent studies validated in large clinical trials with the anti-VEGF antibody, bevacizumab, demonstrated significant clinical benefit and renewed enthusiasm for this therapeutic strategy. This review highlights the challenges related to choosing appropriate strategies for the selection of patients, study design, and choice of appropriate endpoints for the study development of these agents.

Prodrugs of 5-fluorouracil (5-FU) have been shown to be as effective as bolus 5-FU and folinic acid (FA) both in the metastatic and adjuvant setting for colon cancer treatment. Currently, oxaliplatin/5-FU is regarded as the standard adjuvant treatment, and improved response rates and prolonged survival support the use of irinotecan or oxaliplatin combined with 5-FU/FA. The use of oral compounds of 5-FU with irinotecan and oxaliplatin in patients with metastatic disease, however, is questionable due to toxicity concerns. Folprecht and Köhne explain why fluoropyrimidines remain an important component of first-line treatment and discuss which patients would benefit from monotherapy with fluoropyrimidines.