Critical Reviews in Oncology/Hematology 84 (2012) 213–223 Management of “unfavourable” carcinoma of unknown primary site: Synthesis of recent literature Eric Yaovi Amela a , Géraldine Lauridant-Philippin a , Sophie Cousin a , Thomas Ryckewaert a , Antoine Adenis a,b , Nicolas Penel a,c,∗ a Department of medical oncology, Centre Oscar Lambret, 3 rue Combemale, 59020 Lille cedex, France b Catholic University Hospital, Lille, France c Research Unit (EA2694), Medical School University, Lille-Nord de France University, France Accepted 14 March 2012 Contents 1. Introduction ......................................................................................................... 214 2. Materials and methods ................................................................................................ 214 2.1. Prognostic scores .............................................................................................. 214 2.2. Phase II clinical trials ........................................................................................... 214 2.3. Phase III trial .................................................................................................. 214 3. Results .............................................................................................................. 214 3.1. Prognostic scores .............................................................................................. 214 3.2. First-line chemotherapy ......................................................................................... 216 3.2.1. General ............................................................................................... 216 3.2.2. Single-agent versus combination chemotherapy ........................................................... 216 3.2.3. Cisplatin-based regimens ............................................................................... 216 3.2.4. Carboplatin-based regimens ............................................................................. 216 3.2.5. Other first-line regimens ................................................................................ 218 3.2.6. Dose-dense, high-dose and complex sequential regimens ................................................... 218 3.3. Second-line regimens ........................................................................................... 218 3.4. Role of molecular targeted therapies ............................................................................. 220 3.5. Phase III trial .................................................................................................. 220 4. Discussion ........................................................................................................... 221 References .......................................................................................................... 221 Biography ........................................................................................................... 223 Abstract Carcinomas of unknown primary (CUP) approximately represent 2–3% of all adult cancers. Various clinicopathological subsets of CUP have been identified, which may be treated with tailored approaches. Nevertheless, 80% of CUP do not fall into these subsets. Even when at least 4 prognostic models have been developed and validated in independent patient cohorts, there is no consensus or reliable guidance for estimating the prognosis of these “unfavourable” CUP. Consequently, targeting patients who benefit from palliative chemotherapy is difficult. Thirty-eight ∗ Corresponding author at: Department of Medical Oncology, Centre Oscar Lambret, 3 rue F Combemale, 59020 Lille, France. Tel.: +33 3 20 29 59 20; fax: +33 3 20 29 59 63. E-mail addresses: n-penel@o-lambret.fr, scientifique@o-lambret.fr, s-marchant@o-lambret.fr (N. Penel). 1040-8428/$ – see front matter © 2012 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.critrevonc.2012.03.003