A phase II study to evaluate the efficacy and toxicity of oxaliplatin in combination with gemcitabine in carcinoma of unknown primary

Background: Preclinical and clinical data suggest synergy for gemcitabine and oxaliplatin. These agents were tested in several known cancers that also comprise the common carcinoma of unknown primary (CUP) subtypes; namely, lung and pancreaticobiliary profiles. Methods: The study enrolled 29 patients of whom 28 patients were eligible for treatment. Gemcitabine was given at 1,000 mg/m² as a fixed dose rate infusion and oxaliplatin was infused at 100 mg/m² every 2 weeks with restaging performed after 3 cycles at 6 weeks. Results: The study reported one complete response (CR) (4%), 6 patients with a partial response (PR) (25%), and 13 with stable disease (SD) (54%); and 4 patients had progressive disease (PD) (17%) on restaging. Median overall survival (OS) and progression-free survival were 12.8 months (95% confidence interval [CI] 8.5-18.5) and 3.1 months (95% CI 1.7-6), respectively. The 1-year OS was 54%. The most common grade 3 toxicities were nausea (22%), vomiting (15%), and fatigue (11%). There were no grade 4 toxicities. This study was closed early as we moved from an empiric therapy platform to a more individualized approach. Conclusions: Gemcitabine and oxaliplatin is a well-tolerated regimen in CUP with similar outcomes to previously documented CUP studies. In selected good performance status patients this combination may serve as a first-line doublet chemotherapy option for CUP patients (clinicaltrials.gov ID:NCT00353145).