Carcinoma of unknown primary site.

Background: The long term survival and toxicity associated with the chemotherapy combination of paclitaxel, carboplatin, and extended-schedule etoposide used for the treatment of patients with metastatic carcinoma of unknown primary site were evaluated.

Methods: Seventy-one patients were treated between March 1995 and November 1996 with paclitaxel, carboplatin, and oral etoposide every 21 days. Stable or responding patients received four to eight courses of therapy. The following histologies were represented: well differentiated adenocarcinoma (34 patients); poorly differentiated adenocarcinoma or poorly differentiated carcinoma (30 patients); poorly differentiated neuroendocrine carcinoma (6 patients); and squamous cell carcinoma (1 patient).

Results: Forty-eight percent of assessable patients had major responses to therapy (95% confidence interval, 39%-55%), and 10 patients (15%) had complete responses. There were no response differences among the major histologic types. The median survival for all 71 patients was 11 months, and the 1-year, 2-year, and 3-year survival rates were 48%, 20%, and 14%, respectively. The minimum follow-up period was 34 months (range, 34-50 mos). The regimen was tolerated well with no treatment-related deaths and only 12 hospitalizations for neutropenia and fever. There was no serious long term toxicity.

Conclusions: In this large Phase II trial, the combination of paclitaxel, carboplatin, and oral etoposide produced major responses or stable disease status in nearly 80% of patients who had carcinoma of unknown primary site. The median survival and 1-year, 2-year, and 3-year survival rates were noteworthy. The current study obtained similar or superior results to those seen with chemotherapy for many other groups of patients, such as those who had well defined advanced malignancies, those who were considered to have responsive tumors, and those who had obtained substantial benefits from cytotoxic therapy. Although the regimen reported in the current study can become an attractive option for many patients with carcinoma of unknown primary site, there remains a need for further clinical trials.