Gene expression profiling is a novel approach to identifying where cancers of unknown primary site (CUP) originate. Whether the use of gene expression profiling in directing site-specific therapy improves outcomes for patients with CUP, however, has not been well studied. In this randomized controlled trial, investigators randomized 130 patients to either site-specific therapy or empiric paclitaxel and carboplatin (PC) in order to examine the effect of gene expression profiling directed site-specific therapy on overall survival and progression-free survival at 1 year. Gene expression was used to successfully predict a tissue of origin for all patients. Investigators found that the median overall survival was 9.8 months (95% CI 5.7 months to 13.8 months) for the site-specific therapy group, and 12.5 months (95% CI 8.9 months to 16.1 months) for the empiric PC group (HR 1.028, 95% CI 0.678 to 1.560, p=0.896). The estimated progression-free survival was 5.1 months (95% CI 1.9 months to 8.3 months) for the site-directed therapy group in comparison to 4.8 months for the empiric PC group (95% CI 3.3 months to 6.5 months) (HR 0.884, 95% CI 0.590 to 1.326, p=0.550). In terms of subgroups, no subgroups showed a benefit of site-specific treatment for overall survival. An effect of site-specific treatment on PFS was suggested in patients with more-responsive tumor types, but results did not reach statistical significance (HR 0.696, 95% CI 0.316 to 1.534, p=0.396). Taken together, the results from this study suggest that site-directed therapy based on microarray profiling does not improve overall survival or progression-free survival compared to empirical treatment, although this study was limited in that there was an imbalance in predicted tumor types between the two arms. Stratification based on predicted tumor types may also be useful in future studies.
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