title: Association Between Proton Pump Inhibitors and Metronomic Capecitabine as Salvage Treatment for Patients With Advanced Gastrointestinal Tumors: A Randomized Phase II Trial.
abstract: The acidification of extracellular compartment represents a conceivable mechanism of drug resistance in malignant cells. In addition, it has been reported to drive proliferation and promote invasion and metastasis. Experimental evidence has shown that proton pump inhibitors can counteract tumor acidification and restore sensitivity to anticancer drugs. Moreover, early clinical data have supported the role of proton pump inhibitors in anticancer treatments. Metronomic capecitabine has demonstrated beneficial effects as salvage chemotherapy for heavily pretreated or frail patients with gastrointestinal cancer. The present study (EudraCT Number: 2013-001096-20) was aimed at investigating the activity and safety of high-dose rabeprazole in combination with metronomic capecitabine in patients with advanced gastrointestinal cancer refractory to standard treatment. A total of 66 patients will be randomized 1:1 to receive capecitabine 1500 mg/daily, continuously with or without rabeprazole 1.5 mg/kg twice a day, 3 days a week until disease progression, undue toxicity, or withdrawal of informed consent. The primary endpoint is progression-free survival. The secondary endpoints are clinical benefit, which reflects the proportion of patients with complete response, partial response, and stable disease, and overall survival. Progression-free and overall survival will be evaluated using a log-rank test to determine the effect of rabeprazole independently at the 2-sided α-level of 0.05. Other assessments will include the frequency and severity of adverse events and changes in laboratory parameters to measure the safety, and the pharmacokinetics of capecitabine. The results are expected in 2016.
authors.affiliation: Department of Molecular and Clinical Medicine, Sapienza University of Rome, Rome, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Marchetti
authors.affiliation: Department of Molecular and Clinical Medicine, Sapienza University of Rome, Rome, Italy.
authors.forename: Annalisa
authors.initials: A
authors.lastname: Milano
authors.affiliation: Department of Molecular and Clinical Medicine, Sapienza University of Rome, Rome, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: D'Antonio
authors.affiliation: Department of Molecular and Clinical Medicine, Sapienza University of Rome, Rome, Italy.
authors.forename: Adriana
authors.initials: A
authors.lastname: Romiti
authors.affiliation: Department of Molecular and Clinical Medicine, Sapienza University of Rome, Rome, Italy. Electronic address: rsfalcone@libero.it.
authors.forename: Rosa
authors.initials: R
authors.lastname: Falcone
authors.affiliation: Department of Molecular and Clinical Medicine, Sapienza University of Rome, Rome, Italy.
authors.forename: Michela
authors.initials: M
authors.lastname: Roberto
authors.affiliation: National Institute of Health, Rome, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Fais
mesh_terms: D059250:Administration, Metronomic; D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects; D000069287:Capecitabine / Q000008:administration & dosage / Q000009:adverse effects; D018572:Disease-Free Survival; D005260:Female; D005770:Gastrointestinal Neoplasms / Q000188:drug therapy* / Q000401:mortality; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D054328:Proton Pump Inhibitors / Q000008:administration & dosage / Q000009:adverse effects; D064750:Rabeprazole / Q000008:administration & dosage / Q000009:adverse effects; D012107:Research Design; D016879:Salvage Therapy / Q000379:methods*
chemical_list: D054328:Proton Pump Inhibitors; D064750:Rabeprazole; D000069287:Capecitabine
keywords: Acidity; Low-dose chemotherapy; Rabeprazole; Refractory disease; Salvage chemotherapy