Cisplatin alone or combined with gemcitabine in carcinomas of unknown primary: Results of the randomised GEFCAPI 02 trial

Purpose To compare the overall survival rates of good-prognosis carcinomas of an unknown primary site (CUPS) patients treated with cisplatin alone (C) or in combination with gemcitabine (CG). Patients and methods Good prognosis was defined according to the GEFCAPI (Groupe d’Etude Francais des Carcinomes de site Primitif Inconnu) classification by PS (Performance Status) ⩽1 and LDH (Lactate Deshydrogenase) within the normal range. Patients were randomly assigned to receive C or CG. Patients in the C arm received cisplatin 100 mg/m2 repeated every 3 weeks. In the CG arm, chemotherapy consisted of gemcitabine 1250 mg/m2 on days 1 and 8 and cisplatin 100 mg/m2 IV on day 1, repeated every 3 weeks. The original plan was to accrue 192 patients in order to detect a 20% difference in overall survival. Results Fifty-two patients were enrolled (arm A: 25; arm B: 27). The trial was stopped early due to insufficient accrual. The median overall survival (OS) rate was 11 months [95% confidence interval: 9–20] and 8 months [95% CI: 6–12], in the CG arm and in the C arm, respectively. The 1-year survival rate was 46% [95% CI: 28–64] in the combination arm and 35% [95% CI: 19–56] in the C arm (log rank test: p = 0.73). The median progression-free survival (PFS) rate was 5 [95% CI: 3–11] and 3 [95% CI: 1–8] months in the CG and in the C arm, respectively. The 1-year PFS rate was 29% [95% CI: 15–48] in the combination arm and 15% [95% CI: 5–35] in the C arm (log rank test: p = 0.27). No toxic deaths occurred. Grade 3–4 neutropenia (63% versus 12%) and grade 3–4 thrombocytopenia (37% versus 4%) were more frequent in the CG arm than in the C arm. Conclusion A non-significantly better outcome was observed with CG as compared to C in patients with CUP and a non-unfavourable prognosis. The toxicity profile of the combined arm was represented by haematologic toxicity with thrombocytopenia and leuconeutropenia. International collaboration is required to conduct phase III trials in patients with CUP.