Abstract 910P
Background
Pantoprazole inhibits the H+/K+ ATP pump, decreasing acidity of the tumor microenvironment, and possibly sensitizing cells to cytotoxic agents.
Methods
A phase I/II randomized controlled trial in adult patients with advanced squamous cell carcinoma of head and neck planned for first-line palliative chemotherapy. Patients included had ECOG PS 0-2 and primaries in oral cavity, oropharynx, hypopharynx, larynx, or cervical adenopathy of unknown origin. The primary objective in the first phase was to determine the safe dose of intravenous pantoprazole combined with systemic therapy. Primary endpoint in phase II was progression free survival; key secondary endpoints were response, toxicity, overall survival and QOL. Stratification was based on primary site, ECOG PS and type of systemic therapy (intravenous cisplatin 75 mg/m2 every 21 days or oral metronomic chemotherapy [OMCT] consisting of oral celecoxib 200 mg twice daily and oral methotrexate 15 mg/m2 weekly). Patients were randomized to chemotherapy alone or intravenous pantoprazole with chemotherapy. Study was approved by institutional ethics committee and registered with Clinical Trials Registry-India (CTRI/2018/02/011824).
Results
The dose of intravenous pantoprazole established in phase I was 240 mg. We recruited 120 patients in phase II from Nov 2018 to Oct 2020, 59 on pantoprazole and 61 on standard arm. Median age was 51 years (range, 27 to 73), 80% were men. Commonest primary site was oral cavity in 73%. Systemic therapy was intravenous cisplatin in 22% and OMCT in 78%. Addition of pantoprazole did not prolong the PFS; 2.20 months (pantoprazole) versus 2.37 months (standard); HR, 0.895; 95% CI, 0.611-1.312; p=0.57. Response rate was similar; pantoprazole-10.4%, standard-8.89%; p=0.346. Overall survival was also similar; 6.75 months (pantoprazole) versus 5.45 months (standard); HR, 0.834; 95% CI, 0.529-1.315; p=0.435. There was no difference in grade ≥ 3 toxicities between the two arms, 46% (pantoprazole) and 43% (standard), p=0.95.
Conclusions
Intravenous pantoprazole when added to systemic therapy does not improve outcomes in patients with advanced head and neck squamous cell cancer.
Clinical trial identification
Registered with Clinical Trials Registry India- CTRI/2018/02/011824.
Editorial acknowledgement
None
Legal entity responsible for the study
Tata Memorial Center, Mumbai, India.
Funding
Lung Cancer Consortium Asia.
Disclosure
V. Noronha: Financial Interests, Institutional, Research Grant, Research grant paid to the institution: Amgen; Financial Interests, Institutional, Research Grant, Research grant paid to the institution: Sanofi India Ltd.; Financial Interests, Institutional, Research Grant, Research grant paid to the institution: Dr. Reddy’s Laboratories Inc; Financial Interests, Institutional, Research Grant, Research grant paid to the institution: Intas Pharmaceuticals ; Financial Interests, Institutional, Research Grant, Research grant paid to the institution: AstraZeneca Pharma India Ltd. K. Prabhash: Financial Interests, Institutional, Research Grant, Research grant paid to the institution: Biocon Ltd.; Financial Interests, Institutional, Research Grant, Research grant paid to the institution: Dr. Reddy's Laboratories Inc.; Financial Interests, Institutional, Research Grant, Research grant paid to the institution: Fressenius Kabi India Pvt Ltd; Financial Interests, Institutional, Research Grant, Research grant paid to the institution: Alkem Laboratories; Financial Interests, Institutional, Research Grant, Research grant paid to the institution: Natco Pharma Ltd.; Financial Interests, Institutional, Research Grant, Research grant paid to the institution: BDR Pharmaceuticals India Pvt. Ltd.; Financial Interests, Institutional, Research Grant, Research grant paid to the institution: Roche Holding AG. All other authors have declared no conflicts of interest.