Although neither of these patients had a response, they both had stable disease (5, 7 mo). It is unclear if there is any benefit in K-ras wild type patients as there were too few patients to analyze in this subset analysis. There are no published clinical trials LDN193189 assessing the utility of sequential therapy with panitumumab after progression on cetuximab or vice versa. There has been one published Inhibitors,research,lifescience,medical study of lapatinib use after monoclonal antibody failure and this study failed to show any clinical benefit with lapatinib monotherapy (21). The optimal arena to test this combination therefore may be prior to EGFR antibody administration in the treatment

of k-ras wild type tumors. There are pre-clinical data suggesting that lapatinib, a tyrosine kinase inhibitor that inhibits the EGFR pathway along with HER-2, may act synergistically with capecitabine through the down regulation of resistance factors such as TS. Our study did not show activity with this regimen, Inhibitors,research,lifescience,medical suggesting that lapatinib was unable to overcome fluoropyrimidine resistance. Our study was designed using the two-stage Simon-Optimal study design. Although the study was designed to be terminated if there were 0 or 1 responses in the first 18 patients, the study Inhibitors,research,lifescience,medical was also designed not to be delayed while the first 18 patients were evaluated for a response. This led to an Inhibitors,research,lifescience,medical additional

11 patients enrolled in our study, for 0 responses in a total of 29 patients. While eliminating suspension of accrual pending an interim analysis can lead to faster accrual, it can also unnecessarily enroll additional patients in studies where the efficacy is in question. We would advocate for halting studies for interim analysis to reduce the number of patients unnecessarily treated with ineffective investigational therapies in clinical studies. The relatively rapid accrual rate, however, highlights the ongoing need for more therapeutic options in this patient

population. In summary, the combination of capecitabine and lapatinib failed Inhibitors,research,lifescience,medical to show any clinical activity in heavily pretreated patients with colorectal adenocarcinoma. Further PD184352 (CI-1040) studies could be considered to evaluate this combination as an oral alternative therapy to an intravenous monoclonal antibody in patients with K-ras wild type tumors without prior monoclonal antibody therapy. Funding This research was supported in part by P30 CA14520. Acknowledgements The investigators appreciate the participation of the members of the Wisconsin Oncology Network in the design conduct of the study. Footnotes No potential conflict of interest.
In this issue of Journal of Gastrointestinal Oncology, Frank et al. present their experience with capecitabine and lapatinib in patients with chemo-resistent colorectal adenocarcinoma (1).