Third, the study assumes no differences between various arms of 5-FU-based therapy in the chemotherapy arm, a finding refuted by prior randomized studies. Is Bax prognostic? In the surgical group that did not receive chemotherapy, patients with elevated Bax had an improved survival.

This would suggest that Bax overexpression is a positive prognostic factor. This could only be hypothesized if the high and Inhibitors,research,lifescience,medical low-Bax patients in the surgery-only arm were matched by stage, grade, and other relevant risk factors. This was not the case. Is Bax/bcl-2 predictive of 5-FU response? In the patient undergoing surgery followed by 5-FU, patients with low bax/bcl-2 has a superior outcome than patients with high Bax/Bcl2. This would suggest that high bax/blc-2 is predictive of 5-FU resistance. This can only be hypothesized if the two groups were matched for other risks of recurrence or progression. This was not the case. Stage heterogeneity, small sample Inhibitors,research,lifescience,medical size, and the heterogeneity of 5-FU-based therapy, significantly limit the results from this study. In addition, Inhibitors,research,lifescience,medical the results do not support

findings from a larger series evaluating the impact of Bax and Bcl2 expression on 5-FU-treated colorectal cancer patients (2). In a study of 188 patients treated with 5-FU based chemotherapy, low Bax expression was associated with a worsened outcome and patients with high Bax expression and low Bcl2 had the best outcome Inhibitors,research,lifescience,medical (2). How do we move forward? This study illustrates the limitations of analyzing subjectively graded variables in a heterogeneous colorectal cancer population. It is time to recognize the complex interactions between variable prognostic markers of progression and disease resistance. Such interactions can only be tested in large patient populations whose baseline characteristics and outcomes were collected in a prospective controlled manner. A quantitative multi-gene RT-PCR

assay for the prediction of recurrence in stage II colon cancer was recently developed by Genome Science using the QUASAR study population (3). While this assay is Inhibitors,research,lifescience,medical somewhat successful in categorizing stage II colon cancer into 3 distinct categories of risk of relapse, it failed to predict for benefit or lack off with 5-FU therapy. Oncotype DX profiling is one step in the right direction, but more work is clearly needed.
Colorectal cancer is the third most common cancer and the second leading cause of cancer death in the United States. In 2010, it is estimated that there will be 142,570 new cases Clinical Microbiology Reviews and 51,370 will die from the disease (1). Because of earlier diagnosis through screening and more effective selleck chemicals llc treatment modalities including surgery, chemotherapy and radiation, over the past 30 years, mortality from colorectal cancer has decreased. Fluoropyrimidines have remained the backbone of standard therapy for colorectal cancer. Common toxicities include diarrhea, stomatitis, and hand-foot syndrome with diarrhea being a dose limiting toxicity in clinical trials.