Journal of Medical Diagnostic Methods
Open Access

Abstract

Multicenter, Open-Label, Phase I/II Study of Tocilizumab, an Anti–Interleukin-6 Receptor Monoclonal Antibody, Combined with Gemcitabine in Patients with Advanced Pancreatic Cancer

Mitsunaga S, Okusaka T, Ikeda M, Ozaka M, Ohkawa S, et al.

Background: To assess the efficacy, safety and pharmacokinetics of tocilizumab + gemcitabine in patients with advanced pancreatic cancer.

Methods: Patients with treatment-naive advanced pancreatic cancer and high inflammatory burden (C-reactive protein ≥ 2 mg/dl) without obvious infections received tocilizumab (8 mg/kg) intravenously every 2 weeks with intravenous gemcitabine (1,000 mg/m2) on days 1, 8 and 15 of each 4-week cycle until disease progression or study withdrawal. Interleukin-6 signalling inhibition biomarkers were measured. Efficacy analyses included overall survival, progression-free survival, tumour response and clinical symptoms. Adverse events and laboratory parameters were also assessed.

Results: Fifteen patients received tocilizumab+gemcitabine. Tumour response was observed in two patients (13%). Six patients (40%) died within 2 months of treatment start. Median overall survival was 2.5 months (95% confidence interval, 1.4-5.8); median progression-free survival was 1.8 months (95% confidence interval, 0.8-3.6). Overall and progression-free survival tended to be longer in patients with modest than in patients with higher elevations of baseline C-reactive protein. Changes in C-reactive protein and IL-6 occurred. Although tocilizumab +gemcitabine was tolerable, results were inconclusive because of the brevity of the evaluation period resulting from the death or premature withdrawal of patients. Dose interruption attributed to haematologic toxicity was frequently observed.

Conclusions: Tocilizumab+gemcitabine failed to show a clear clinical benefit in patients with advanced pancreatic cancer and high inflammatory burden. To evaluate conclusively the benefit of tocilizumab, future study designs should use a comparator treatment that does not interfere with interleukin-6 signalling and that includes better patient selection criteria.