Capecitabine, an oral prodrug of 5-fluorouracil (5-FU), is a promising treatment for colorectal, breast and gastric cancers, but often causes hand-foot syndrome (HFS), the most common dose-limiting toxicity. The current study was conducted to investigate the relationship between HFS and efficacy of capecitabine in 98 patients with metastatic breast cancer. Possible associations between HFS and efficacy endpoints, including time-to-treatment failure (TTF), tumor response in metastatic lesions and changes in tumor markers, were investigated retrospectively using electronic medical records. The TTF of group with HFS of grade 1 and ≥2 was significantly longer than that of group with no HFS, respectively (hazard ratio (HR), 0.39; 95% confidence interval (CI), 0.18-0.87 for group with grade 1; HR, 0.42, 95% CI, 0.19-0.90 for group with grade ≥2). Significantly higher disease control rates for the liver metastasis were observed in patients with HFS (grade 1 and greater) than in those without HFS (92.9 vs. 42.9%, p 0.009). Furthermore, prevention of increases in tumor marker levels (carcinoembryonic antigen (CEA), carbohydrate antigen 15-3 (CA15-3) and National Cancer Center-Stomach-439 (NCC-ST439)) was evident in patients with HFS. This study clearly showed a significant correlation between HFS and some efficacy markers of capecitabine therapy in patients with metastatic breast cancer, and suggests that early dose adjustment based on severity of HFS might improve efficacy. Studies are needed to explore predictive biomarkers for HFS/efficacy, so that capecitabine therapy can be further tailored to patient response.Key words capecitabine; hand-foot syndrome; efficacy; electronic medical record Capecitabine is administered as an oral fluoropyrimidine prodrug in the treatment of a number of cancers, including breast and gastrointestinal cancers. 1) Capecitabine generates 5-fluorouracil (5-FU) preferentially in tumor tissue through a three-step enzymatic process. In the first step, capecitabine is hydrolyzed by carboxylesterase (CES) in the liver to produce the 5′-deoxy-5-fluorocytidine (5′-DFCR). In the second step, 5′-DFCR is converted to 5′-deoxy-5-fluorouridine (5′-DFUR) by cytidine deaminase (CDA), which is highly active in liver and tumor tissues.2) In the final step, 5′-DFUR is converted to 5-FU by thymidine phosphorylase (TP), a rate-limiting enzyme. Dihydropyrimidine dehydrogenase (DPYD), a ratelimiting catabolic enzyme of the pyrimidines, is also involved in the degradation pathway of capecitabine.1,3) Since TP activity is 3-10 times higher in tumor cells than in the normal tissues, 2,4) selective conversion of capecitabine to 5-FU in tumor tissues minimizes systemic exposure to 5-FU relative to exposures associated with intravenous (i.v.) 5-FU/leukovorin regimens. Thus, capecitabine is associated with a lesser incidence of 5-FU-related severe toxicities, such as diarrhea, stomatitis, nausea, alopecia and neutropenia, while maintaining equivalent or superior efficacy compared with the IV regimens. 5-7)The most com...

Background Objective evaluation of the physical activity (PA) in patients with chronic obstructive pulmonary disease (COPD) is important. We validated a triaxial accelerometer, Active Style Pro HJA-750C® (HJA), and evaluated the necessary conditions for obtaining reproducible data. Methods The PA measured by HJA was compared with that measured by two already validated accelerometers in 11 patients with COPD (age: 76.6 ± 6.9, FEV1% predicted: 57.6 ± 18.6). Then, the influence of weather and holidays on the PA and the required number of days to obtain repeatability were examined in 21 patients with COPD (age: 73.0 ± 8.0, FEV1% predicted: 58.7 ± 19.0). Results The PA values measured by HJA and those by DynaPort Move Monitor® (DMM) or Actimarker® (AM) were significantly correlated at all intensities (p=0.024 at ≥4.0 METs by DMM and p < 0.0001 at the rest) except at ≥4.0 METs by AM, though the values measured by HJA were higher than those by AM which was reported to underestimate PA. The durations of PA on rainy days were significantly shorter than those on nonrainy days, but those on holidays were not different from those on weekdays. The values of ICC for 3, 4, or 5 days were higher than 0.8 at all intensities. The PA measured by HJA was correlated with the dyspnea scale FVC and age and tended to correlate with FEV1. Conclusions The HJA was validated for evaluating the PA in patients with COPD. This trial is registered with UMIN000016363.

What is known and Objective: Demonstration of the utility of electronic medical records (EMRs) for pharmacovigilance (PV) has been highly anticipated. Analysis using appropriately selected EMRs should enable accurate estimation of adverse drug event (ADE) frequencies and thus promote appropriate regulatory actions. Statin-induced myopathy (SIM) is a clinically important ADE, but pharmacoepidemiological methodology for detecting this ADE with high predictability has not yet been established. This study aimed to develop a detection algorithm, highly selective for SIM using EMRs. Methods: We collected EMRs on prescriptions, laboratory tests, diagnoses and medical practices from the hospital information system of Kobe University Hospital, Japan, for a total of 5109 patients who received a statin prescription from April 2006 to March 2009. The current algorithm for extracting SIM-suspected patients consisted of three steps: (i) event detection: increase in creatine kinase (CK) and subsequent statin discontinuation, (ii) filtration by exclusion factors (disease diagnosis/medical practices) and (iii) refinement by the time course of CK values (baseline, event and recovery). A causal relationship between the event and statin prescription (probable/possible/unlikely) was judged by review of patient medical charts by experienced pharmacists. The utility of the current algorithm was assessed by calculating the positive predictive value (PPV). In a comparative analysis, subjects screened in step 1 were extracted by the diagnostic term/code for 'myopathy/rhabdomyolysis', and the PPV of this diagnostic data approach was also estimated. Results and Discussion: Five subjects with suspected SIM were identified using our proposed algorithm, giving a frequency of 0Á1% for the adverse event. Review of the medical charts revealed that the causal association of SIM with statin use was judged as 'Likely (probable/possible)' for all five suspected patients; thus, the PPV was estimated as 100% (95% confidence interval: 56Á6-100%). The higher utility of the current algorithm compared with the diagnostic data approach was also shown by assessing the PPV (100 vs. 33Á3%). What is new and Conclusion:We report on a detection algorithm with high predictability for SIM using EMRs. Combined use of exclusion criteria for disease, medical practice data and time course of CK values contributes to better prediction of SIM. The utility of the proposed algorithm should be further confirmed in a larger study.

The MPM patients with PS 0-2 and Hb concentration >12.1 or ≤12.1 g dL(-1) without chest pain had favourable prognoses.

The PFS-HR and OS-HR were strongly correlated in advanced NSCLC patients treated with post-first-line anticancer agents, with a SPP of less than 6 months.