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Because cytidine deaminase (CDA) is the key enzyme in gemcitabine metabolism, numerous studies have attempted to investigate impact of CDA status (i.e. genotype or phenotype) on clinical outcome. To date, data are still controversial because none of these studies has fully investigated genotype-phenotype CDA status, pharmacokinetics and clinical outcome relationships in gemcitabine-treated patients. Besides, most patients were treated with gemcitabine associated with other drugs, thus adding a confounding factor. We performed a multicenter prospective clinical trial in gemcitabine-treated patients which aimed at investigating the link between CDA deficiency on the occurrence of severe toxicities and on pharmacokinetics, and studying CDA genotype-phenotype relationships.One hundred twenty patients with resected pancreatic adenocarcinoma eligible for adjuvant gemcitabine monotherapy were enrolled in this study promoted and managed by the Fédération Francophone de Cancérologie Digestive. Toxicities were graded according to National Cancer Institute's Common Terminology Criteria for Adverse Events Version 4. They were considered severe for grade ≥ 3, and early when occurring during the first eight weeks of treatment. CDA status was evaluated using a double approach: genotyping for 79A>C and functional testing. Therapeutic drug monitoring of gemcitabine and its metabolite were performed on the first course of gemcitabine.Five patients out of 120 (i.e., 4.6%) were found to be CDA deficient (i.e., CDA activity

BACKGROUND:Gastrointestinal stromal tumors (GISTs) are rare, but represent the most common mesenchymal neoplasms of the gastrointestinal tract. EPIdemiology GIST, is an observational multicenter longitudinal follow-up cohort study reporting the prescribing patterns of imatinib in patients with GIST and the impact of the treatment in a real-world (standard clinical) setting. METHODS:Eligible patients had a confirmed diagnosis of unresectable or metastatic KIT-positive GIST and started treatment with imatinib for the first time between May 24, 2002, and June 30, 2010. During routine visits, annual collection of clinical characteristics was requested, i.e., age, GIST stage at diagnosis, history, imatinib treatment duration and dosage, adherence, and concomitant medications. Survival outcomes were estimated using the Kaplan-Meier method. Other data were analyzed using descriptive statistics. RESULTS:Of 151 patients enrolled, imatinib was initiated for 126 patients before enrollment and for 25 patients on the day of enrollment or soon after. The patient characteristics were similar to those in published prospective trials. The estimated 1-, 2-, 3-, and 4-year overall survival rates were 90.4% (95% confidence interval [CI; 84.8%-94.0%]), 84.7% (95% CI [78.1%-89.4%]), 73.0% (95% CI [65.0%-79.4%]), and 60.7% (95% CI [51.4%-68.8%]), respectively. The most common adverse events (AEs) were diarrhea (39%), asthenia (39%), eyelid or periorbital edema (32%), abdominal pain (23%), and anemia (21%). Eight of 126 serious AEs were possibly related to the treatment as assessed by investigators. CONCLUSIONS:Study results showed that patients in real-life populations are generally treated in accordance with national and international clinical recommendations and have outcomes comparable to those of patients in clinical trials.