[Efficacy of AboundTM for hand-foot syndrome caused by capecitabine].

Hand-foot syndrome( HFS) has been reported to be the most common adverse effect of capecitabine, with an incidence of more than 50%. AboundTM, containing ß-hydroxy-ß-methyl butyric acid( HMB), L-glutamine, and L-arginine is effective in the treatment of decubitus ulcers and in wound healing; however, whether AboundTM is efficacious for HFS caused by capecitabine is not clear. This study aimed at evaluating the effectiveness of AboundTM in the recovery from HFS caused by capecitabine. Capecitabine administration was discontinued in 6 patients with more than grade 2 HFS, and AboundTM was administered. The time to recovery was examined. The median time to recovery to less than grade 1 HFS was 10 days( range, 4-14 days). The grade of HFS decreased following the administration of AboundTM. The findings of this study suggest that AboundTM is effective against HFS caused by capecitabine.

[Evaluation of outpatient clinical pathway, including the supportive therapy of S-1+cisplatin combination therapy for gastric cancer].

S-1+cisplatin (CDDP) combination therapy is a standard regimen for advanced gastric cancer and is usually administered within the hospital environment. Recently, ambulatory chemotherapy has been applied to treat various cancers. For the realization of outpatient treatment, it is necessary to strengthen supportive therapy. We developed a comprehensive and supportive care clinical pathway. The use of this pathway in combination with the expertise of pharmacists has resulted in enhanced supportive therapy, reduced side effects, and increased treatment intensity.

[Examination of factors influencing continuity of S-1 adjuvant chemotherapy for gastric cancer patients].

After Adjuvant Chemotherapy Trial of S-1 for Gastric Cancer(ACTS-GC), adjuvant chemotherapy with S-1 is a standard treatment for stage II or III gastric cancer patients. In this study, we retrospectively examined factors that influence the continuity of S-1 adjuvant chemotherapy. We analyzed the clinical documentation of 27 gastric cancer patients being treated with S-1 adjuvant chemotherapy. Patients who completed the treatment without reduction dose were classified into a complete group(n=14), and those for whom S-1 was discontinued or reduced due to adverse reactions were classified into a reduced/discontinuation group(n=13). First, we examined the background factors at baseline between these two groups. Univariate logistic regression analysis revealed that the operative procedure, leukocyte count, and serum creatinine level at baseline were identified as factors that influence the continuity of S-1 chemotherapy. Next, we investigated the hematological and nutritional conditions of these patients during the treatment period. The loss of body mass index(BMI)during the treatment period was remarkable in the reduced/discontinuation group regardless of the operative procedure. This result suggests that an early nutritional intervention might be important for gastric cancer patients undergoing S-1 adjuvant chemotherapy.

[Gastrojejunostomy followed by chemotherapy with S-1 in unresectable gastric cancer with pyloric stenosis].

We investigated the efficacy of gastrojejunostomy followed by S-1-based chemotherapy for unresectable gastric cancer with pyloric stenosis. We performed gastrojejunostomy and S-1-based chemotherapy in 14 unresectable gastric cancer patients with gastric outlet obstructions between April 2006 and June 2010. Although there were two complications after surgery, no treatment-related deaths were observed. The response rate of the S-1-based chemotherapy was 41.7%, and the median survival after surgery was 12.3 months. All patients were tolerating a regular diet and a significant improvement in oral intake lasted for at least 6 months. In conclusion, gastrojejunostomy followed by chemotherapy with S-1 appears to be an effective treatment modality for unresectable gastric cancer with pyloric stenosis. It enables us to practice S-1-based standard chemotherapy for advanced gastric cancer and improve the quality of life of patients.

[Assessment of nausea and vomiting during FEC regimen for breast cancer after the novel antiemetic agent - introduction using MASCC antiemesis tool].

Chemotherapy-induced nausea and vomiting(CINV)is one of the side effects causing significant psychological and physical suffering in patients receiving chemotherapy. Because CINV often impairs patients' quality of life and leads to discontinuation of treatments, antiemetic therapy has been considered important. The MASCC Antiemesis Tool(MAT)was proposed for the assessment of acute and delayed nausea and vomiting after, we evaluated the actual situation of nausea and vomiting for Japanese patients. In a previous investigation, even conventional antiemesis therapy was a highly effective treatment during the acute phase, but the control of nausea and vomiting during the delayed phase proved difficult. Recently, a new5 -HT3 receptor blocker(palonosetron)and an NK1 receptor blocker(aprepitant) were introduced, and an effective treatment of nausea and vomiting for the delayed phase is non expected. In this examination, we evaluated the usefulness of the new antiemetic drugs(palonosetron and aprepitant)in 12 prospective patients with breast cancer(40-69 years old, median age 53 years old)for whom FEC therapy was given as an ambulant treatment using MAT. No vomiting occurred in the acute and delayed phase. Nausea during the acute phase was controlled, and was mild during the delayed phase, also. It was confirmed that the onset of acute and delayed nausea and vomiting were relieved by the newantiemetic agents compared with the previous MAT evaluation.

[Evaluation of the S-1 granule forms in gastric cancer patients who received treatment with S-1 capsule-questionnaire survey about drug dosage forms].

The S-1(tegafur/gimeracil/oteracil potassium)granule was developed to meet the needs of patients with cancer. Although the choice of the patients was thought to spread by the addition of the new agent type, the recognition of the S-1 granule is still low and you should adapt yourself to what kind of patients or are unknown. Therefore, we conducted a questionnaire survey of patients with gastric cancer undergoing treatment with S-1 capsules to investigate the adaptation and taste of the patients. As a result, although it was the investigation by the patients during S-1 capsule remedy, it was replied when 21. 3%(13/61 case)'had good granule,'and all cases raised it by the reason of there'not being the sense of incongruity of the throat at taking.'Also, about the global assessment of granule, the proportion of patient who replied'very good'or'good'were 31. 1% and 47%, in all cases and in the cases that felt the sense of incongruity of the throat during S-1 capsule remedy, respectively. Therefore, in the patients treated with the S-1 capsule, there were thought to be the patients who expected treatment with a granule. By the results of this survey, it was found that it is necessary to perform a medical teaching including dosage form to contribute to the adherence improvement of the patients.

Individual differences in rate-limiting reactions during metabolism of irinotecan hydrochloride.

UNLABELLED: Irinotecan hydrochloride (CPT-11) is converted to SN-38 by carboxylesterase, SN-38 is conjugated by UDP-glucuronosyl- transferase (UGT) to SN-38G. Individual differences in enzyme activity influence the efficacy of this anticancer agent and the adverse reactions it induces. In this study, individual differences in the metabolism of this drug were determined by calculating its c 1 on version (CPT-11 to SN-38) and conjugation ratios (SN-38 to SN-38G) from blood concentrations of CPT-11, SN-38, and SN-38G at immediately and 60 min after a 90-min intravenous infusion of CPT-11. Changes in conversion and conjugation during long-term infusion of CPT-11 were also investigated. The median conversion and conjugation ratios were 0.0155 and 2.812, respectively (n=48). Based on these values, the patients were classified into four types: low-low type (10.4%), low-high type (31.2%), high-low type (31.2%), and high high type (27.1%). Prolongation of infusion time resulted in an increase in the conversion ratio in the low-high type and an increase in the conjugation ratio in the high-low type. These changes, however, were very slight in the high-high type. Thus, a longer infusion time made it possible to increase the number of doses in the low-high type and minimize adverse reactions in the high-low type. CONCLUSION: In patients found to have a low SN-38 conversion ratio or SN-38G conjugation ratio based on simple assessment of data obtained by 2-point blood sampling, modification of infusion time may allow pharmacokinetic changes that confer a clinical benefit.

[Improvement of urinary d-glucaric acid assay and its application].

We propose an improved method to measure urinary D-glucaric acid (GA), which might be of value as an indirect index of the activity of cytochrome P450 (CYP). This method was about 20 times more sensitive than existing methods. Beer's law was obeyed in the concentration range 5.5-66 ng ml(-1) for GA, with the effective molar absorptivity at 533 nm and the relative standard deviation being 9.1 x 10(5) dm(3) mol(-1) cm(-1) and 0.69% (n = 6), respectively. In addition, we introduced the correction value {GA/Cr ratio x10} of urinary GA by measuring urinary creatinine (Cr) at the same time. Based on the proposed method, the GA and Cr values in spot urines of healthy persons and cancer patients were subsequently measured and the correction values of both groups subjected to comparison. As a result, a statistically significant difference was recognized between the two groups.

[Support of TS-1, 5-FU preparation containing potent DPD inhibitor by determination of urinary uracil/serum 5-FU clearance].

Though FU-derived anticancer agents are metabolized and detoxicated by dihydropyrimidine dehydrogenase (DPD), its wide distribution of activity is concerned primarily in the antitumor effects or side effects of 5-FU. In recent years, it has become possible to predict the metabolism of FU-derived anticancer agents by DPD activity through the determination of urinary uracil levels. In the present study, therefore, we examined whether or not urinary uracil levels could be used as a predictor for as certaining the efficacy and/or side effects of TS-1, which contains a potent DPD inhibitor. Consequently, the following relationship was revealed to exist between urinary uracil levels and clinical effects of TS-1: 1) The effect of TS-1 administration was generally good in patients whose uracil level was within the standard values with no presentation of serious side effects. 2) The administration of TS-1 was also useful even in patients whose uracil levels were below the standard value. 3) Though no side effects were observed when a conventional FU-derived anticancer agent was administered to patients showing an urinary uracil level below the standard value, some side effects appeared when TS-1 was administered. Under present circumstances where understanding of genome diagnosis and establishment of informed consent are rather difficult, this approach of predicting DPD activities through the determination of urinary uracil levels seems to be of help for deciding a therapeutic regimen based on the patient's constitutional features when a cancer chemotherapy with TS-1 is performed.