Cetuximab-based treatment of metastatic anal cancer: correlation of response with KRAS mutational status.

Background: No standard chemotherapy regimen can be defined for patients with metastatic squamous cell carcinoma of the anus due to the low incidence of this disease and the high cure rate of localized tumors. Anal cancers universally express the epidermal growth factor receptor (EGFR) and KRAS mutations have not been reported in anal cancer thus far.
Methods: We report on 7 patients with metastatic anal cancer treated with cetuximab - a chimeric antibody against EGFR - on a compassionate use basis along with the results of KRAS mutational analysis.
Results: Marked tumor shrinkage was noted in several patients using cetuximab monotherapy or cetuximab/irinotecan combination as first or subsequent treatment line (usually after failure of cisplatin-based regimens). Two out of seven patients harbored KRAS mutations. Both patients had progressive disease receiving cetuximab, while the remaining 5 patients had either a partial remission (n = 3), a minor remission (n = 1) or no change lasting > or =6 months after previous rapid tumor progression.
Conclusion: Cetuximab-based treatment appears to be a valuable treatment option for patients with metastatic KRAS wild-type anal cancer after failure of or as an alternative to cisplatin/5-fluorouracil-based therapy.
(Copyright 2009 S. Karger AG, Basel.)