Proton pump inhibitors as anti vacuolar-ATPases drugs: Preliminary findings in companion animals with spontaneous neoplasms treated with metronomic chemotherapy

Abstract

Event Abstract Back to Event Proton pump inhibitors as anti vacuolar-ATPases drugs: Preliminary findings in companion animals with spontaneous neoplasms treated with metronomic chemotherapy Enrico Spugnini1* and Stefano Fais2 1 Regina Elena Cancer Institute, Italy 2 Istituto Supriore di Sanita, Italy Background and aim. The vacuolar ATPases are ATP-dependent proton pumps whose functions include the acidification of intracellular compartments and the extrusion of protons through the cell cytoplasmic membrane. These pumps play a pivotal role in the regulation of cell pH in normal cells and, to a much greater extent, in tumor cells. In fact, the glucose metabolism in hypoxic conditions by the neoplasms lead to an intercellular pH drift towards acidity. The acid microenvironment is modulated through the over-expression of H+ transporters that are also involved in tumor progression, invasiveness, distant spread and chemoresistance. Aim of the study was the evaluation of tolerability and efficacy of high dose proton pump inhibitors in dogs carrying relapsing or chemoresistant neoplasms. Methods. Dogs and cats with down/staged spontaneous neoplasms or with chemoresistant tumors were treated with omeprazole at the dose of 5 mg/kg from Monday through Wednesday and 1 mg/kg from Thursday to Saturday, combine with metronomic chemotherapy and a water alkalizer. Gastro-intestinal toxocity was scored accordingly to the Veterinary Comparative Oncology Group guidelines. Response to treatment was assessed on the basis of clinical evalutation and confirmatory biopsies. Results. Fourteen pets (thirteen dogs and one cat) have been recruited over a 18 months period. Age ranged from 8 to 15 years. Tumor types included: 1) anal sac carcinoma with sublumbar metastases T3N1M0; 2) thyroid carcinoma T4N0M1; 3) Liver sarcoma T3N1Mx; 4) Liver carcinoma T4N0M0; 5) Neck soft tissue grade III sarcoma TiN0M0; 6) Splenic HSA T3N1Mx; 7) Splenic HSA T3N0Mx; 8) inflammatory mammary carcinoma T3N1M0; 9) Metastatic mammary carcinoma T3N1M0; 10) Mammary carcinoma grade III T0NxMx (adjuvant therapy); 11) Soft tissue limb sarcoma T3NxM1; 12) Adenocarcinoma of nasal sinuses (T2N0M0); 13) Foreleg grade III anaplastic sarcoma T0NxMx (adjuvant therapy); 14) The cat had nasal chondrosarcoma T2N0M0. The treatment was overall well tolerated, one dog had mild diarrhea but continued the therapy albeit at a decreased dose. The responses were: Three complete remissions, 7 partial responses, 6 no evidence of disease (adjuvant therapy group). Conclusions / Discussion. The pump inhibitor lansoprazolo, administered at high dose has proven to enhance chemosensitivity and to prolong survival time in a spontaneous pet tumor modes and could be a useful addition to the current options for refractory neoplasms in consideration of its low cost, limited toxicity, and ease of administration.