Cancer of unknown primary site (CUP) is a heterogeneous group of cancers with widely varying natural histories and biological characteristics for which the anatomical site of origin remains occult after detailed investigations.Several clinicopathological subsets with favorable prognosis have been identified.CUP presents a clinical situation quite difficult to manage due to the absence of a standard of care for the initial therapeutic approach, as well as an impossibility to include these cases in randomized clinical trials.Historically, a "favorable subset" designation was made based on a presentation that overwhelmingly suggested a specific primary origin.Although several clinicopathologic subsets with favorable prognosis have been identified, most patients do not fit into any of these subsets.CUP is often associated with a poor prognosis, as patients are usually treated with a non-selective empirical therapy.During the past 3 decades, some phase II trials of platinum-based combination regimens containing newer cytotoxic agents (taxanes, gemcitabine, irinotecan, etc.) resulted in response rates of 20%-60% and median survivals of 6-11 months.In these trials, taxane-based regimens showed better responses and longer survivals.Therefore, taxane-platinum regimens as empiric chemotherapy are widely used for these patients.In the current paper, we summarize both the therapeutic challenges for patients with CUP as well as the current available therapeutic options, and introduce our trial currently in progress for this population.
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