High dose lansoprazole combined with metronomic chemotherapy: a phase I-II study in companion animals with spontaneously occurring tumorsReportar como inadecuado




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Journal of Translational Medicine

, 12:225

Combination strategies

Abstract

BackgroundThe treatment of human cancer has been seriously hampered for decades by resistance to chemotherapeutic drugs. A very efficient mechanism of tumor resistance to drugs is the proton pumps-mediated acidification of tumor microenvironment. Metronomic chemotherapy has shown efficacy in adjuvant fashion as well as in the treatment of pets with advanced disease. Moreover, we have shown in veterinary clinical settings that pre-treatment with proton-pumps inhibitors PPI increases tumor responsiveness to chemotherapeutics. In this study pet with spontaneously occurring cancer have been recruited to be treated by a combination of metronomic chemotherapy and high dose PPIs and their responses have been matched to those of a historical control of ten patients treated with metronomic chemotherapy alone.

MethodsSingle arm, non randomized phase II open study, with historical control group, evaluating safety and efficacy of the combination of metronomic chemotherapy and alkalization. Twenty-four companion animals 22 dogs and 2 cats were treated adding to their metronomic chemotherapy protocol the pump inhibitor lansoprazole at high dose, and a water alkalizer. Their responses have been evaluated by clinical and instrumental evaluation and matched to those of the control group.

ResultsThe protocol was overall well tolerated, with only two dogs experiencing side effects due to gastric hypochlorhydria consisting with vomiting and or diarrhea. In terms of overall response, in the alkalized cohort, 18 out of 24 had partial or complete responses 75%, two patients had a stable disease and the remaining patients experienced no response or progressive disease. On the other hand, only one patient in the control group experienced a complete response 10% and three other experienced short lived responses. Median time to terminal event was 34 weeks for the experimental group versus 2 weeks in the controls p= 0.042.

ConclusionsPatient alkalization has shown to be well tolerated and to increase tumor response to metronomic chemotherapy as well the quality of life in pets with advanced cancer. Further studies are warranted to assess the efficacy of this strategy in patients with advanced cancers in companion animals as well as in humans.

KeywordsChlorambucil Cyclophosphamide Lansoprazole Piroxicam Proton pump Water alkalizer Electronic supplementary materialThe online version of this article doi:10.1186-s12967-014-0225-y contains supplementary material, which is available to authorized users.

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Autor: Enrico P Spugnini - Sabrina Buglioni - Francesca Carocci - Menicagli Francesco - Bruno Vincenzi - Maurizio Fanciulli - Stef

Fuente: https://link.springer.com/







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