Pre-therapeutic DPYD pharmacogenetic test to prevent fluoropyrimidines (FL)-related toxicities is not yet common practice in medical oncology. We aimed at investigating the clinical validity of DPYD genetic analysis in a large series of oncological patients. Six hundred three cancer patients, treated with FL, have been retrospectively tested for eight DPYD polymorphisms (DPYD-rs3918290, DPYD-rs55886062, DPYD-rs67376798, DPYD-rs2297595, DPYD-rs1801160, DPYD-rs1801158, DPYDrs1801159, DPYD-rs17376848) for association with Grade 3 toxicity, developed within the first three cycles of therapy. DPYD-rs3918290 and DPYD-rs67376798 were associated to Grade 3 toxicity after bootstrap validation and Bonferroni correction (p 5 0.003, p 5 0.048). DPYD-rs55886062 was not significant likely due to its low allelic frequency, nonetheless one out of two heterozygous patients (compound heterozygous with DPYD-rs3918290) died from toxicity after one cycle. Test specificity for the analysis of DPYD-rs3918290, DPYD-rs55886062 and DPYD-rs67376798 was assessed to 99%. Among the seven patients carrying one variant DPYD-rs3918290, DPYD-rs55886062 or DPYD-rs67376798 allele, not developing Grade 3 toxicity, 57% needed a FL dose or schedule modification for moderate chronic toxicity. No other DPYD polymorphism was associated with Grade 3 toxicity. Our data demonstrate the clinical validity and specificity of the DPYD-rs3918290, DPYDrs55886062, DPYD-rs67376798 genotyping test to prevent FL-related Grade 3 toxicity and to preserve treatment compliance, and support its introduction in the clinical practice.The identification of the genetic bases of inter-individual variability in terms of response or toxicity to pharmacological treatments is a key point in the field of personalized therapy. Specifically, in the oncological setting the high variability observed in the tumor response to treatment and in the severity of toxicity emphasizes the importance of improving the knowledge on the clinical validity of the pharmacogenetic tests.Fluoropyrimidines (FL) are listed among the drugs with pharmacogenetic warnings. 1 Despite the acknowledged efficacy of these drugs in the treatment of different solid tumors, 2 the FL treatment remains challenging as a result of a considerable inter-patient variability in terms of efficacy and toxicity. 3,4 The pharmacogenetic research, aimed at defining predictive markers of FL response, mainly focused on the dihydropyrimidine dehydrogenase (DPD), which is the first and rate-limiting enzyme of FL catabolic pathway. Up to date, 160 single nucleotide polymorphisms (SNPs) that alter the DPD aminoacids sequence have been identified within the gene (DPYD) codifying for this enzyme 5,6 and many clinical studies have been trying to investigate their association with FL-related severe toxicities. 3,[7][8][9][10][11] Recently the discussion in the scientific community about the clinical effectiveness of pharmacogenetics has given rise to the publication of drug dosing guidelines with indications and recommendations about drug...

We report on the first case of a catheter-related recurrent bacteremia caused by Kocuria kristinae, a gram-positive microorganism belonging to the family Micrococcaceae, in a 51-year-old woman with ovarian cancer. This unusual pathogen may cause opportunistic infections in patients with severe underlying diseases. CASE REPORTIn December 1999, a 51-year-old woman with abundant ascites and an irregular pelvic mass was referred to the Centro di Riferimento Oncologico of Aviano. Histologic examination of the pelvic mass revealed the presence of a poorly differentiated ovarian carcinoma. In January 2000, a permanent central venous catheter (CVC) was implanted and the patient began chemotherapy. In June 2000, after five courses of chemotherapy, the patient was readmitted for febrile neutropenia and sepsis. Complete clinical and microbiological diagnostic procedures were performed, and four pairs of blood specimens were collected from peripheral blood and the CVC for culture (both aerobic and anaerobic). A gram-positive microorganism identified as Kocuria kristinae grew from three samples cultured aerobically. The patient was empirically treated with meropenem; after the isolation of gram-positive cocci from the bloodstream, a glycopeptide was added, resulting in prompt clinical improvement. No further bacterial isolates were obtained from blood or other clinical samples. The patient was discharged from the hospital, but 1 month later she was readmitted to the Centro di Riferimento Oncologico of Aviano for another febrile episode. Among 11 blood specimens drawn from peripheral blood and the CVC, 7 specimens cultured aerobically again revealed K. kristinae; antibiotic therapy with ciprofloxacin and clindamycin was started, with resolution of fever and negativity of blood cultures. A third febrile episode occurred 1 month later. One of the two blood samples collected from the CVC and cultured aerobically yielded K. kristinae. The CVC was removed and sent to the microbiology laboratory; a gram-positive coccus, which was identified as K. kristinae, was isolated from the culture of the catheter tip. Soon after catheter removal the patient became afebrile and her clinical status improved. After 6 months of monitoring, the patient is alive and well and is in complete remission of the primary disease. Microbiology.Cultures of blood from peripheral veins and the CVC were performed with a BACTEC system (BACTEC 9210; Becton Dickinson) with BACTEC PLUS Aerobic/F and PLUS Anaerobic/F culture vials. The CVC tip was cultured by the quantitative technique of Cleri et al. (5). Briefly, after catheter removal, a 5-cm segment of the tip was vortexed for 30 to 60 s in 5 ml of tryptic soy broth. Three aliquots of the broth (100, 10, and 1 l) were spread onto three sheep blood agar plates. The plates were incubated at 37°C for 18 h. More than 1,000 CFU was counted; this value is considered representative of a catheter infection. The microorganisms isolated from the peripheral blood and the CVC during the different septic episodes and from t...

Defining biomarkers that predict therapeutic effects and adverse events is a crucial mandate to guide patient selection for personalized cancer treatments. In the present study, we applied a pharmacometabolomics approach to identify biomarkers potentially associated with pathological complete response to trastuzumab-paclitaxel neoadjuvant therapy in HER-2 positive breast cancer patients. Based on histological response the 34 patients enrolled in the study were subdivided into two groups: good responders (n = 15) and poor responders (n = 19). The pre-treatment serum targeted metabolomics profile of all patients were analyzed by liquid chromatography tandem mass spectrometry and the differences in the metabolomics profile between the two groups was investigated by multivariate partial least squares discrimination analysis. The most relevant metabolites that differentiate the two groups of patients were spermidine and tryptophan. The Good responders showed higher levels of spermidine and lower amounts of tryptophan compared with the poor responders (p < 0.001, q < 0.05). The serum level of these two metabolites identified patients who achieved a pathological complete response with a sensitivity of 90% [0.79–1.00] and a specificity of 0.87% [0.67–1.00]. These preliminary results support the role played by the individual patients' metabolism in determining the response to cancer treatments and may be a useful tool to select patients that are more likely to benefit from the trastuzumab-paclitaxel treatment.

EMI is as frequent as rest ischemia during 5-FU infusion. Patients undergoing 5-FU continuous infusions should be adviced to avoid unusual efforts, to refer any cardiac symptom, and should be investigated for EMI.