Repurposing pantoprazole in combination with systemic therapy in advanced head and neck squamous cell carcinoma: A phase I/II randomized study

Abstract Background: Pantoprazole decreases acidity of the tumor-microenvironment by inhibiting proton pumps on the cancer cell. This possibly leads to increased sensitivity to cytotoxic therapy. Methods: We conducted a phase I/II RCT in adult head and neck squamous cell carcinoma(HNSCC) patients planned for first-line palliative chemotherapy. Patients were randomized to chemotherapy +/- Intravenous Pantoprazole. Primary endpoint in phase I was to determine the maximum safe dose of Intravenous Pantoprazole whereas it was progression free survival(PFS) in phase II. Results: The dose of IV Pantoprazole established in phase I was 240mg. Between Nov’18 and Oct’20, we recruited 120 patients in phase II, 59 on Pantoprazole and 61 on Standard arm. Median age was 51 years (IQR 43-60), 80% were men. Systemic therapy was Intravenous Cisplatin in 22% and Oral-Metronomic-Chemotherapy(OMC) in 78%. Addition of Pantoprazole did not prolong PFS, 2.2months (95%CI, 2.07-3.19) in the Pantoprazole arm and 2.5months (95%CI, 2.04-3.81, HR, 1.14; 95%CI 0.78-1.66; P=0.48) in the standard arm. Response rates were similar; Pantoprazole arm 8.5%, standard arm 6.6%; P=0.175. OS was also similar; 5.6months (95%CI, 4.47-8.51) in the Pantoprazole arm and 5.4months (95%CI, 3.48-8.54, HR 1.06; 95%CI 0.72-1.57; P=0.75) in the standard arm. Grade >3 toxicities were similar. Conclusion: Intravenous Pantoprazole 240mg added to systemic therapy does not improve outcomes in patients with advanced HNSCC.