Combination regimen with carboplatin, epirubicin and etoposide in metastatic carcinomas of unknown primary site: A Hellenic Co-Operative Oncology Group phase II study

The encouraging results that have been reported for cisplatin combination chemotherapy in a minority of patients with cancer of unknown primary (CUP) together with the previously shown equal activity of carboplatin in this setting, prompted us to investigate the effectiveness of a carboplatin-containing regimen in a phase II clinical trial. Sixty-two evaluable CUP patients entered the protocol. The chemotherapy regimen consisted of carboplatin 300 mg/m(2) IV DI, epirubicin 45 mg/m(2) IV DI and etoposide 120 mg/m(2) IV D1-3 (CEE regimen) administered every 3 weeks. The median age of the patients was 61 years and 36 were male. Thirty-one diagnosed as poorly differentiated carcinomas (pdc) and the rest as adenocarcinomas. By clinicopathological criteria, 14 patients had a predominately nodal disease with pdc or poorly differentiated adenocarcinomas (pda), 3 women peritoneal carcinomatosis, and the remaining 46 patients had a predominately splanchnic involvement (24 pdc, 22 pda). Twenty-three patients responded to chemotherapy with 4 (6.5%) complete and 19 (30.5%) partial responders (RR 37%, 95 % CI 25-49 %). An equal activity of the regimen was observed between the two major histopathological types, the pde and the adenocarcinomas. Nevertheless, significant differences were seen when the CEE regimen was assessed for its activity in the distinct clinicopathological subsets of CUP. Patients with predominately nodal disease of midline distribution with pdc or pda, and women with peritoneal carcinomatosis, achieved a response rate of 64 and 62% respectively, as compared with a 26% response rate for those with predominately splanchnic involvement. Overall median survival was 10 months and for patients with midline distribution 15 months. The regimen was well tolerated. It is concluded that CEE is a relatively non-toxic chemotherapy regimen and easily administered on an outpatient basis. This prospective phase II study confirmed the activity of carboplatin in the chemosensitive subsets of the predominately nodal disease of midline distribution and peritoneal carcinomatosis in women in the CUP syndrome.