Adherence and awareness of the therapeutic intent of oral anticancer agents in an outpatient setting.

The aim of the present study was to clarify the adherence and awareness of oral anticancer agents by type and therapeutic purpose in outpatients prescribed with tegafur/gimeracil/oteracil potassium (S-1) or capecitabine. Outpatients undergoing treatment with the S-1 or capecitabine oral anticancer agents at Ogaki Municipal Hospital (Ogaki, Japan) in June 2013 completed a questionnaire survey and the survey findings were evaluated. No significant differences in medication adherence were identified between the patients administered S-1 and the patients administered capecitabine (P=0.4586). In addition, no significant differences were identified in therapeutic purpose between adjuvant therapy, and advanced and recurrent therapies. However, for S-1 and capecitabine, medication adherence was significantly higher in those undergoing combination therapy compared with those undergoing monotherapy (P=0.0046). In addition, for patients taking S-1, the median age for good adherence was significantly lower than that for insufficient adherence (66.1±10.5 vs. 72.1±7.9 years, respectively; P=0.0035). Furthermore, a significant negative correlation was identified between the awareness score of research regarding the medication and age (n=109; P=0.0045). In conclusion, for patients treated with S-1 or capecitabine, the type and therapeutic purpose of oral anticancer agents did not affect medication adherence. Elderly patients expressed a low interest in medications and typically exhibited insufficient medication adherence. Therefore, patient guidance by pharmacists is important, as it may result in improved medication adherence and an improved understanding of the treatment side-effects in patients self-administering prescribed drugs.

Oral anticancer agent medication adherence by outpatients.

In the present study, medication adherence and factors affecting adherence were examined in patients taking oral anticancer agents. In June 2013, 172 outpatients who had been prescribed oral anticancer agents by Ogaki Municipal Hospital (Ogaki, Gifu, Japan) completed a questionnaire survey, with answers rated on a five-point Likert scale. The factors that affect medication adherence were evaluated using a customer satisfaction (CS) analysis. For patients with good and insufficient adherence to medication, the median ages were 66 years (range, 21-85 years) and 73 years (range, 30-90 years), respectively (P=0.0004), while the median dosing time was 131 days (range, 3-3,585 days) and 219 days (24-3,465 days), respectively (P=0.0447). In 36.0% (62 out of 172) of the cases, there was insufficient medication adherence; 64.5% of those cases (40 out of 62) showed good medication compliance (4-5 point rating score). However, these patients did not fully understand the effects or side-effects of the drugs, giving a score of three points or less. The percentage of patients with good medication compliance was 87.2% (150 out of 172). Through the CS analysis, three items, the interest in the drug, the desire to consult about the drug and the condition of the patient, were extracted as items for improvement. Overall, the medication compliance of the patients taking the oral anticancer agents was good, but the medication adherence was insufficient. To improve medication adherence, a better understanding of the effectiveness and necessity of drugs and their side-effects is required. In addition, the interest of patients in their medication should be encouraged and intervention should be tailored to the condition of the patient. These steps should lead to improved medication adherence.

[Continuation of chemotherapy with bevacizumab for advanced and recurrent colorectal cancer].

We evaluated the association between the number of treatment courses with the concomitant use of bevacizumab(BV) and the reasons for discontinuation of the regimen in patients who received FOLFOX with or without BV as first-line chemotherapy and FOLFIRI with or without BV as second-line chemotherapy for advanced and recurrent colorectal cancer. In first-line treatment, 12 (2-46) and 10 (2-60) treatment courses were administered with and without BV, respectively, and this difference was not significant (p=0.60). In second-line treatment after first-line treatment with the concomitant use of BV, 11 (1-23) and 3 (1-12) treatment courses were administered with and without BV, respectively, and this difference was significant (p<0.01). Discontinuation due to adverse reactions was more frequent for first-line treatment (34.9%) than for second-line treatment (6.2%; p<0.01). The reasons for discontinuation due to adverse reactions during first-line treatment with BV were often associated with BV, and those during first-line treatment without BV were most often associated with peripheral neuropathy. Therefore, we conclude that early detection and prevention of adverse reactions are important in first-line treatment and that pharmacists as well should be involved in the monitoring and management of adverse reactions, although continued administration of BV even during second-line treatment after first-line treatment with BV is recommended.

[Tolerable evaluation for chemotherapy with S-1 plus cisplatin in elderly patients with advanced and recurrent gastric cancer].

This retrospective study examined the extent to which S-1 plus cisplatin is applicable to the elderly as a primary therapy for advanced or recurrent gastric cancer. Subjects under age 70 were categorized as the L group(n=42), and those age 70 and over were categorized as the O group(n=18). The 2 groups were compared in terms of their creatinine clearance(Ccr), performance status(PS), dose intensity(DI), reasons for regimen modification or discontinuation, and adverse reactions. The DI of S-1 was 100(50-100)% in the L group and 83(67-100)% in the H group(p<0. 0001), and the DI of cisplatin was 100(70-100)% in the L group and 87(75-100)% in the H group(p<0. 0001). The incidence of adverse reactions was similar for both groups. However, the S-1 plus cisplatin regimen was discontinued either at the patient's request, or based on the physician's determination that there were adverse reactions such as fatigue or anorexia. There were significantly more of these reactions in the H group(72. 2%)in comparison to the L group(42. 9%)(p=0. 0369). The elderly often had complications, and a decrease in PS as a result of repeatedly undergoing chemotherapy was noted(p=0. 0185). In conclusion, the elderly may have a low tolerance to S-1 plus cisplatin. When administering cancer chemotherapy to the elderly aged 70 and older, the patient's renal function, PS and Ccr, should be studied, and a regimen and dosage should be carefully selected.

[The frequency and risk factor of herpes zoster infection in non-Hodgkin's lymphoma patients].

The chemotherapy treatment of non-Hodgkin's lymphoma(NHL)is associated with an increased risk of infection because of the intensity of the treatment. We examined the frequency of herpes zoster infections in 170 non-Hodgkin's lymphoma patients who had completed a chemotherapy course. Furthermore, we examined the risk factors contributing to these infections. This study took place in the Department of Hematology at Ogaki Municipal Hospital. Of the 170 patients treated in our facility, 25 developed herpes zoster(14. 7%), 19 of whom developed symptoms within 30 days of starting the chemotherapy treatment. Significant risk factors for the development of herpes zoster were post-autologous peripheral blood stem cell transplantation, relapsing patients, ten or more total treatments and the use of two or more regimens. In these cases the average interval of the treatments had to be extended from 6. 6 days to 14. 2 days due to the infection(comparing post - infection to pre-infection). We recommend the prophylactic use of low-dose acyclovir in patients with a higher risk of herpes zoster infection. We also recommend further monitoring of other opportunistic infections associated with chemotherapy usage.

[Continuous administration and safety of S-1 in adjuvant chemotherapy for gastric cancer].

Patients taking more than 8 courses of S-1 were classified in the continuous group (n=30) and those in whom S-1 was discontinued or reduced due to adverse reactions in the discontinuation/reduction group (n=29). Factors affecting the continuous administration of S-1 as the adjuvant chemotherapy were examined in the two groups. 10 cases in the continuous group and 8 cases in the discontinuation/reduction group began with a stage 1 reduction of the S-1 regimen. Significant factors which affected the reduction or discontinuation of S-1 due to adverse reactions were 1) serum albumin value (Alb) (odds ratio 9.227; 95% confidence interval 1.056-80.603, p=0.0196) and 2) creatinine clearance value (Ccr) (odds ratio 5.850; 95% confidence interval 1. 222-27.995, p=0.0221). Among the reasons for reduction or discontinuation, non-hematotoxicities including malaise, nausea and diarrhea accounted for 24/59 cases (40.7%) and hematotoxicities such as leukopenia for 5/59 cases (8.5%). The present study revealed that most of the reduction or discontinuation of S-1 was due to non-hematotoxicity such as malaise and suggested that these risks increased when Alb decreased to less than 3.5 g/dL and Ccr to less than 80 mL/min. Prognosis is reportedly satisfactory when administration of S-1 is continued for one year even if withdrawal or reduction is necessary during the period. Serious adverse reactions will have ill effects on future compliance with to administration in patients who have experienced them. The above results indicate that the occurrence of non-hematotoxicity should be observed carefully in patients with Alb less than 3.5 g/dL and Ccr less than 80 mL/min at the beginning of S-1 administration, and these patients should receive appropriate guidance. Modification or reduction of S-1 regimen at the beginning may be one way to alleviate hematotoxicity.

[Comparative safety evaluation of first- and second-line therapy with carboplatin + paclitaxel for advanced non-small cell lung cancer].

The study was carried out to compare the incidence of hematological toxicity between 14 cases with CDDP+VNR as first line therapy followed by CBDCA+PTX as second-line therapy, and 21 cases with CBDCA+PTX as first-line therapy for nonsmall cell lung cancer. The incidences of thrombocytopenia were 78. 6% in the second-line and 42. 9% in the first-line with a significant difference (p=0. 0364). The incidences of neutropenia at grade 3 or more in the second-line and the first-line were 71. 4% and 52. 4%, respectively, with a tendency to be higher in the second-line. When creatinine values increased by 25%or more, even though they were within normal limits, following the CDDP+VNR in the first-line, the occurrence of neutropenia at grade 3 or more was significant (p=0. 016) in the first-course of the second-line therapy comprising CBDCA+PTX. The present findings suggest that when CBDCA+PTX therapy is performed following CDDP+VNR therapy, renal functions must be observed carefully, including changes in creatinine, during the CDDP+VNR therapy. When doses are determined for CBDCA+PTX as second-line therapy, dose reduction may be one of methods used to avoid serious hematological toxicity.

[Clinical evaluation of calculating carboplatin doses using modification of diet in renal disease (MDRD) estimate and adverse events].

A modified diet in renal disease (MDRD), a formula to estimate glomerular filtration rate (GFR), was proposed by Levey in 2006. In this study, we compared the dosage of carboplatin (CBDCA) calculated using MDRD with that calculated by conservative creatinine clearance (Ccr), and investigated the actual dosage given and the incidence of its adverse effects. In the 101 patients undergoing chemotherapy including CBDCA, the dosage calculated from the estimated GFR was 16% lower than that based on the estimated Ccr. This difference was greater in those under 65 years, women and those with a body mass index (BMI) > or =25. The most prominent incidence of adverse effects was thrombocytopenia in patients with lung cancer. In men, a serum creatinine level of > or =0. 6 mg/dL, GFR of <50 mL/min/1. 73 m(2) and a combined use of gemcitabine were cited as the factors responsible for the development of thrombocytopenia. It was concluded that the MDRD formula is an effective tool for evaluating patients with impaired renal function. It was suggested, on the other hand, that the dosage for medication should be decided by giving due consideration to factors other than renal functions.

Increased in vitro release of interferon-gamma from ampicillin-stimulated peripheral blood mononuclear cells in Stevens-Johnson syndrome.

Stevens-Johnson syndrome (SJS) was diagnosed in a 39-year-old woman, treated with ampicillin (4000-8000 mg daily), phenytoin (250 mg daily), and furosemide (20-40 mg daily) for 25, 21, and 20 d, respectively, before the appearance of the eruption. The lymphocyte stimulation test with the MTT [3-(4,5-dimethyl thiazol-2-yl)-2,5-diphenyl tetrazolium bromide] assay on ampicillin, phenytoin, and furosemide showed a low value of stimulation index, which indicated negative reactivity. An in vitro IFN-gamma release test was conducted on the patient with SJS and on two healthy controls. IFN-gamma release increased by 52% following the in vitro challenge of the patient's peripheral blood mononuclear cells (PBMCs) with 15 microg/ml of ampicillin, but not with phenytoin or furosemide. Neither of the controls experienced increased IFN-gamma release. In the present case, increased in vitro IFN-gamma release was observed on ampicillin-stimulated PBMCs, which may indicate the role of ampicillin as the drug responsible for the induction of SJS, and may imply the role of IFN-gamma in the pathogenesis of SJS.

[Effects of pesticides on cytokines production by human peripheral blood mononuclear cells--fenitrothion and glyphosate].

In patients with pesticides poisoning, human immune system seems to be damaged. However, the effects of pesticides on human immune system, especially on cytokines production, have not been understood well. We investigated the effects of fenitrothion (MEP), an organophosphorus insecticide, and glyphosate (GLP), a phosphorus containing amino acid-type herbicide, on cytokines production by human peripheral blood mononuclear cells (PBMC). MEP inhibited the proliferative activity of PBMC at ranging from 1 to 500 microM in a concentration-dependent manner, whereas GLP had a slight inhibitory effect even at 1000 microM. The production of IFN-gamma and IL-2 was inhibited by MEP in a concentration-dependent manner, but GLP slightly inhibited their production only at 1000 microM. The production of TNF-alpha and IL-1 beta was not affected by MEP and GLP at the concentrations which significantly inhibited the proliferative activity and T cell-derived cytokine production. MEP inhibited the production of T cell-derived cytokine (IFN-gamma and IL-2), which indicates that MEP might have the potential of immunosuppressive action. On the other hand, GLP might be a pesticide with only a little damage to the immune system, according to the results in cytokines production. These results suggest that pesticides inhibit the immune system differently, and the grasp of immune condition might be useful for the prognostic presumption and the infectious danger of degree in patients with pesticides poisoning.