BACKGROUND: Cancer of unknown primary (CUP) lacks established therapy although 
it affects 3% of cancer patients. We evaluated the irinotecan-oxaliplatin 
combination (IROX regimen) in previously untreated patients with non-favorable 
subsets of unknown primary carcinomas.
METHODS: This was a multicenter phase-II trial. Protocol treatment consisted of 
oxaliplatin 80 mg/m(2) followed by irinotecan 160 mg/m(2) administered every 3 
weeks. The primary end points were response rate and toxicity, and secondary end 
points were time to progression and survival.
RESULTS: Forty-seven patients with liver, bone or multiple visceral metastases 
entered into the trial and received a median 6 chemotherapy cycles (1-11). The 
regimen was very well tolerated with one febrile neutropenia case and six cases 
with diarrhea grade 3 (16%). In intent-to-treat analysis the tumor response rate 
was 13% (95% CI = 4.8-25.7%) and 12 patients (27%, 95%CI 13.9-40.4%) had at 
least 4 months' duration of disease stabilization. The median time to 
progression was 2.7 months and the median survival was 9.5 months, with 40% of 
patients alive at 1 year.
CONCLUSIONS: The IROX regimen demonstrated similar efficacy and a favorable 
toxicity profile compared to other more toxic chemotherapy combinations in 
patients with poor-prognosis CUP.