The aim of the study was to assess the clinical activity and toxicity of oxaliplatin and leucovorin in combination with bolus and continuous infusion of 5-fluorouracil treated every 2 weeks (modified FOLFOX-6 regimen) in patients with adenocardinoma of unknown primary (ACUP).
Previously untreated ACUP patients were enrolled and treated with oxaliplatin 100mg/m2 and leucovorin 200mg/m2 simultaneously as 2-hour infusion followed by bolus administration of 5-fluorouracil 400mg/m2 and continuous infusion of 5-fluorouracil 2400mg/m2 every 2 weeks. Response evaluation was performed every 3 cycles according to the response assessment in solid tumours version 1.1, and toxicities were assessed using the National Cancer Institute Common Toxicity Criteria for adverse events version 3.0 every 2 weeks.
Data from 23 patients who had been enrolled in this multicenter phase II trial between May 2009 and Nov 2014 was collected for an interim analysis. A total of 134 cycles of modified FOLFOX-6 were treated in these 23 patients. The median number of cycles of modified FOLFOX-6 was 5 (range, 1–12). Among 20 patients whose tumor responses were evaluable, 7 patients showed partial response (no complete response), which objective response rate was 35.0% (95% confidence interval: 13.2 - 52.9). The median duration of response was 3.9 months (range, 3.0–19.8). Median progression-free survival was 3.0 months (95% CI: 1.8–6.7 months) in whole patients, which was 2.4 months for non-responders and 5.8 months for responders, respectively. Adverse events of all grade occurred in 22 patients (95.7%), and a grade ≥ 3 event occurred in 7 patients (30.4%). Grade ≥ 3 hematologic toxicities occurred in 4 patients (17.4%), and grade ≥ 3 non-hematologic toxicities occurred in 6 patients (26.1%), respectively. Most common hematologic toxicities were anemia and neutropenia (78.3% and 65.2%, respectively), while nausea was most frequent non-hematologic toxicity (47.8%).
Modified FOLFOX-6 showed modest activity in treatment-naÃ¯ve patients with ACUP. Future prospective large scale study incorporating parallel molecular prediction marker study is warranted.
Clinical trial identification
WHO-ICTRP ID: KCT0000410
All authors have declared no conflicts of interest.