Non-steroidal anti-inflammatory drugs induce severe hematologic toxicities in lung cancer patients receiving pemetrexed plus carboplatin: A retrospective cohort study.

PURPOSE: As the major toxicity induced by pemetrexed plus carboplatin is severe hematologic toxicities, the aim of this study was to determine the risk factors for severe hematologic toxicities in lung cancer patients. METHODS: We retrospectively investigated data from lung cancer patients who had received pemetrexed plus carboplatin, with or without bevacizumab. This observational study was carried out at Ehime University Hospital using electronic medical records dating from July 2009 to March 2015. Severe hematologic toxicities were defined as grade 3 or 4, according to the Common Terminology Criteria for Adverse Events, version 4.0. RESULTS: Forty-two patients were included in the study. The incidence of grade 3 or 4 hematologic toxicities during the first cycle of chemotherapy and during all cycles was 19.0% and 16.1%, respectively. Multivariate time-depend generalized estimating equations logistic regression analysis revealed that regular use of non-steroidal anti-inflammatory drugs (NSAIDs) was significantly associated with an increased risk of severe hematologic toxicities during all cycles (adjusted odds ratio (OR): 8.32, 95% confidence interval (CI): 1.27-54.38; p = 0.03), whereas creatinine clearance of <45 mL/min was not significantly associated with an increased risk of severe hematologic toxicities during all cycles (adjusted OR: 0.91, 95% CI: 0.25-3.34; p = 0.88). CONCLUSIONS: The results suggest that severe hematologic toxicities in patients receiving carboplatin-based pemetrexed may be significantly induced by the inhibition of renal tubular pemetrexed secretion through drug-drug interactions between NSAIDs and pemetrexed rather than through glomerular filtration of pemetrexed, even with moderate to sufficient renal function.

Risk factors for discontinuation of s-1 adjuvant chemotherapy for gastric cancer.

PURPOSE: The aim of this study was to clarify the risk factors for discontinuing tegafur/gimeracil/oteracil potassium (S-1) adjuvant chemotherapy following gastrectomy in patients with gastric cancer. METHODS: We retrospectively investigated patients with curatively-resected gastric cancer who received S-1 adjuvant chemotherapy. S-1 was administered orally at 80-120 mg/day, depending on body surface area, on days 1-28 every 6 weeks for 1 year. The dose and treatment schedule were modified at the clinicians' discretion, according to toxicity. RESULTS: Seventy-one patients were included in the study, 26 of whom discontinued S-1 therapy. The relapse-free survival rates in the S-1-completed and S-1-discontinuation groups at 5 years post-surgery were 88.1% and 55.8%, respectively. The overall survival rates in the S-1-completed and S-1-discontinuation groups at 5 years post-surgery were 89.4% and 59.8%, respectively. The hazard ratios for relapse and death were significantly lower in the S-1-completed group compared with those in the S-1-discontinuation group (0.18; p<0.001 and 0.19; p=0.002, respectively). Multivariate logistic regression analysis revealed that S-1 discontinuation was significantly associated with an initial overdose of S-1, having stage I cancer, creatinine clearance <66 mL/min, and a side effect of nausea. CONCLUSIONS: These results suggest that assessing renal function to avoid initial overdose of S-1, together with the early management of side effects, may support the continuation of S-1 adjuvant chemotherapy in patients with gastric cancer.

[Evaluation of experience-oriented hospital practical training by an examination].

Ehime University Hospital has been conducting a four-week practical hospital training course, consisting of 18 programs, for undergraduate students. The course includes experience-oriented programs, such as drug counseling training using case-based learning procedures (CBL practice), evidence based medicine (EBM practice) based on the provision of drug information, and training to avoid adverse drug reactions (pre-avoid practice). A previous study based on a questionnaire survey showed that experience-oriented programs enhanced students' understanding of the hospital practical training, while also increasing their satisfaction. In this trial, written examinations were given to 24 students to evaluate their clinical knowledge and problem-solving abilities at the start and the end of the practical hospital training course to evaluate the educational effects of this curriculum objectively. The problem-solving abilities were examined using a test of a case analysis, which required the students to answer multiple clinical problems or proposals. The examination scores on the clinical knowledge at the end of the practical hospital training course had significantly increased by 9.5% (p<0.01) in comparison to that at the start. In addition, the accuracy rate regarding their problem-solving abilities markedly increased by 28.8% (p<0.001). Moreover, the number of answers also significantly increased by about 1.5-fold (p<0.001). These results suggested that the experience-oriented programs for hospital practical training increased the clinical knowledge and the problem-solving abilities of these students.