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

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Abstract

Pantoprazole decreases the acidity of the tumor microenvironment by inhibiting proton pumps on the cancer cell. This possibly leads to increased sensitivity to cytotoxic therapy. We conducted a phase I/II randomized controlled trial in adult patients with head and neck squamous cell carcinoma (HNSCC) planned for first-line palliative chemotherapy. Patients were randomized to chemotherapy + / − intravenous (IV) pantoprazole. The 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. The dose of IV pantoprazole established in phase I was 240 mg. Between Nov’18 and Oct’20, we recruited 120 patients in phase II, 59 on pantoprazole and 61 on the standard arm. Median age was 51 years (IQR 43–60), 80% were men. Systemic therapy was IV cisplatin in 22% and oral-metronomic-chemotherapy (OMC) in 78%. Addition of pantoprazole did not prolong PFS, which was 2.2 months (95% CI 2.07–3.19) in the pantoprazole arm and 2.5 months (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. Overall survival was also similar; 5.6 months (95% CI 4.47–8.51) in the pantoprazole arm and 5.4 months (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. Thus, pantoprazole 240 mg IV added to systemic therapy does not improve outcomes in patients with advanced HNSCC.

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Funding

This study was supported by the Lung Cancer Consortium Asia.

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Authors and Affiliations

  1. Department of Medical Oncology, Tata Memorial Hospital, Homi Bhabha National Institute, Mumbai, India

    Vanita Noronha, Nandini Menon, Ajaykumar Singh, Minit Shah, Supriya Goud, Kunal Jobanputra, Kavita Nawale, Srushti Shah, Oindrila Roy Chowdhury, Vijayalakshmi Mathrudev, Shweta Jogdhankar, Madhu Yadav Singh & Ashish Singh

  2. Department of Medical Oncology, P D Hinduja Hospital & Medical Research Centre, Khar & Mahim, India

    Vijay Patil

  3. Department of Clinical Operations, ImmunoAdoptive Cell Therapy Private Limited, R-977, Rabale Navi, Mumbai, 400701, India

    Devanshi Kalra

  4. Department of Clinical Operations, Senior Clinical Study Monitor, DAVA Oncology LP, 2700 W Plano Pkwy, Plano, TX, 75075, USA

    Supriya Adak

  5. Department of Clinical Medicine, Danish Center for Particle Therapy, Aarhus University Hospital, 8200, Aarhus, Denmark

    Mayuri Sandesh

  6. Department of Cardiothoracic and Vascular Surgery, JIPMER, Puducherry, India

    R. Arunkumar

  7. Department of Radiodiagnosis, Tata Memorial Hospital, Homi Bhabha National Institute, Mumbai, India

    Suman Kumar

  8. Department of Radiodiagnosis, The Clatterbridge Cancer Centre NHS Foundation Trust, University of Liverpool, Liverpool, UK

    Abhishek Mahajan

  9. Department of Medical Oncology, Solid Unit, Tata Memorial Hospital, Homi Bhabha National Institute, Parel, Mumbai, 400012, India

    Kumar Prabhash

  10. Department of Clinical Medicine, Aarhus University, 8200, Aarhus, Denmark

    Mayuri Sandesh

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  1. Vanita Noronha
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Correspondence to Kumar Prabhash.

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Conflict of interest

Vanita Noronha has received funding from Amgen (Inst); AstraZeneca (Inst); Dr. Reddy's Laboratories (Inst); INTAS (Inst); Sanofi/Aventis (Inst). Vijay Patil received funding from AstraZeneca (Inst); Eisai Germany (Inst); INTAS (Inst); Johnson & Johnson/Janssen (Inst); NATCO Pharma (Inst); Novartis (Inst). Kumar Prabhash has received funding from Alkem Laboratories (Inst); BDR Pharmaceutics (Inst); Biocon (Inst); Dr. Reddy's Laboratories (Inst); Fresenius Kabi (Inst); NATCO Pharma (Inst); Roche (Inst). None of the other authors declared any conflict of interest.

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Noronha, V., Patil, V., Menon, N. et al. Repurposing pantoprazole in combination with systemic therapy in advanced head and neck squamous cell carcinoma: a phase I/II randomized study. Med Oncol 41, 26 (2024). https://doi.org/10.1007/s12032-023-02234-z

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