A phase II study of cisplatin, etoposide and gemcitabine in an unfavourable group of patients with carcinoma of unknown primary site

Background: The aim of this phase II study was to determine toxicity, response rate, time to progression, and overall survival of cisplatin, etoposide and gemcitabine in patients with carcinoma of unknown primary tumour site. Patients and methods: Thirty patients with no previous chemotherapy and not belonging to a treatable group were treated with cisplatin 70 mg/m(2) on day 1, etoposide 70 mg/m(2) on days 1 and 2, and gemcitabine 700 mg m(2) days 1 and 8, administered every 3 weeks. Stable or responding patients received a maximum of eight cycles. Twenty patients (67%) had more than three affected sites, and 25 patients (84%) had adenocarcinomas. Results: Overall response rate was 36.6% (11 patients), including four complete responses (13.3%) and seven partial responses (23.3%), with a 95% confidence interval of 19.9-56. Median survival was 7.21 months and eight patients remained alive for >1 year. Myelosuppression was the most important toxicity, with grade 3-4 neutropenia in 18 patients (60%) in 32% of the cycles: eight patients had neutropenic fever and 10 patients had thrombopenia in 11% of cycles. No non-haematological grade 4 toxicity occurred. Conclusions: Cisplatin, etoposide and gemcitabine is an active combination, inducing objective responses in a subset of heavily advanced disease patients with carcinoma of unknown primary site. The role of adding gemcitabine to cisplatin and etoposide remains to be resolved as to the best schedule to diminish toxicity for the three-drug combination.