Carboplatin, doxorubicin and etoposide in the treatment of tumours of unknown primary site

Unknown primary tumours (UPTs) are now recognised as an autonomous, although heterogeneous, nosographic entity, with considerable clinical relevance, as they account for 5% of all tumours. Until recently they were approached with more emphasis on diagnosis than on treatment. Much emphasis was placed on trying to ascertain the site of origin of the tumour. This approach is slowly being discarded, at least in reported series, although it widely resists in clinical practice, in particular in non-specialised centres. There are two main reasons for abandoning extensive investigation in an attempt to find the site of origin. Extensive diagnostic procedures cause discomfort for the patient, require time and cause delay of treatment. In addition, they are often fruitless (Hainsworth and Greco, 1993; Abbruzzese et al, 1995; Schapira and Jarrett, 1995). For the minority of tumours that have been identified in the last two decades as being potentially sensitive to chemotherapy (van der Gaast et al, 1990; Pavlidis et al, 1992; Abbruzzese et al, 1995; Lenzi et al, 1997; Greco and Hainsworth, 2001b), the diagnostic procedures will delay these patients from receiving effective treatment. By restricting diagnostic procedures to a minimum, and with an early start of chemotherapy, median survival has improved from 3–6 months of the past (Altman and Cadman, 1986; Alberts et al, 1989) to around 1 year in recently reported series (Briasoulis et al, 2000; Greco et al, 2000a). We have conducted a multicentre phase II trial in patients with UPT, where diagnostic procedures were limited and where treatment was started soon after presentation. Although in autopsy series the majority of patients with UPT are diagnosed with diseases poorly responsive to treatment (Nystrom et al, 1977), there is a substantial minority of patients with primary tumours that are sensitive to chemotherapy, such as germ cell tumours, ovarian and breast cancer. The regimen chosen for this study, a combination of carboplatin, doxorubicin and etoposide, contains drugs active against these more chemosensitive tumours, and employed at dosages potentially able to induce major responses We considered that if an improvement of response rate occurred, this might result in improved outcome for an unselected group of patients with UPTs, and that this would justify the anticipated toxicity of the regimen. This paper describes the results with emphasis on response to treatment, toxicity and survival.