Predictive testing for erythropoietin induced tumor progression in head and neck cancer

Abstract

11007 Background: Although anemia is an independent poor prognostic factor in cancer, its correction using erythropoietin (Epo) may promote cancer progression and reduce survival, as suggested by several recent Phase III trials. We tested whether measuring Epo receptor (EpoR) mRNA levels in head and neck cancer could identify patients susceptible to Epo induced tumor growth. We also examined whether endogenous Epo might stimulate tumor growth. Methods: We measured EpoR mRNA levels in tumors from a previously reported Phase III trial in which 351 patients irradiated for head and neck cancer were randomized to Epo or placebo (Henke et al., Lancet 2003). 154 of these tumors had been evaluated previously with a polyclonal antibody raised against the human EpoR (C20) (Henke et al., J Clin Oncol 2006), but which also cross reacts with non-EpoR proteins (Elliott et al., Blood 2006). EpoR mRNA levels were measured in 106 tumors. We examined the relationship between EpoR mRNA level and locoregional progression free survival (LPFS), the primary study endpoint, in subjects assigned to Epo versus placebo. For patients enrolled in the placebo arm we also compared baseline serum Epo levels, C20 status, EpoR mRNA levels, and LPFS. Results: Epo-treated patients with unresected tumors that expressed above-median EpoR mRNA levels experienced a reduction in LPFS compared to the placebo group (p=0.02, n=s effect was not observed in patients with unresected tumors that expressed below-median EpoR mRNA levels (p=0.80, n=14). EpoR mRNA levels had no effect in patients with completely resected or partially resected tumors. In placebo patients with unresected or incompletely resected tumors, increased Epo levels were associated with impaired LPFS if their tumors were C20 positive (p=0.02, n=22), and improved LPFS if their tumors were C20 negative (p=0.09, n=15). C20 status and EpoR mRNA levels did not correlate (r=−0.11). Conclusion: Adverse effects of Epo on tumor progression may depend on tumor EpoR expression. Whether a relationship exists between other C20 targets and Epo induced tumor progression deserves further exploration. Our findings present clear hypotheses that should be tested in archival tumors from other Phase III trials. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Hoffman-La Roche