[Establishment of a Needle-Removal Method Considering Anticancer Drug Exposure after Continuous Administration of Fluorouracil Using an Infusion Pump].

In recent years, attention has been focused on environmental exposure of anticancer drugs, and guidelines for occupational exposure measures in cancer drug therapy have been created in Japan. Exposure measures related to the preparation and administration of anticancer drugs are being standardized. Although exposure measures have been implemented for the preparation and administration of the infusion pump(IP)used for continuous fluorouracil administration for 46-hour in FOLFOX and FOLFIRI therapies, which are standard chemotherapies for colorectal cancer, needle-removal procedures after the end of administration have not been investigated. Therefore, in this study, we investigated anticancer drug exposure at the time of IP needle removal to establish a safe needle-removal procedure from the viewpoint of anticancer drug exposure countermeasures. The results suggest that the IP's clamp lock position and the pulsing flush of the Huber needle may reduce antineoplastic exposure. In the future, we would like to consider this an educational method for needle-removal techniques.

[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.

[Examination of continuity of S-1 adjuvant chemotherapy for gastric cancer patients after gastrectomy].

Next to ACTS-GC (Adjuvant Chemotherapy Trial of S-1 for Gastric Cancer), adjuvant chemotherapy with S-1 is the standard treatment for stage II or III gastric cancer patients.In this study, we retrospectively examined the continuity and adverse reaction of S-1 adjuvant chemotherapy in 30 gastric cancer patients who visited our hospital from 2007 to 2008, and compared them with those of patients treated with ACTS-GC. Whereas the persistent rate of S-1 adjuvant chemotherapy for one year in ACTS-GC was 65.8%, it was 86.7% in our hospital.The RP (Relative performance) value in cases who completed S-1 adjuvant therapy for one year in ACTS-GC and for one year in our hospital was 81.2% and 88.5%, respectively. Grade 3/4 adverse events in our hospital were leukopenia (3.3%), neutropenia (16.7%), and anorexia(6.7%). In conclusion, our hospital has shown a far greater continuity with S- 1 adjuvant chemotherapy than with ACTS-GC, a result suggesting that S-1 adjuvant chemotherapy is feasible in clinical practice.

[Equalization of breast cancer chemotherapy at general hospital( II )-evaluation of safety in FEC and TC regimens].

The safety of epirubicin (75 mg/m(2)), 5-fluorouracil (500 mg/m(2)) plus cyclophosphamide (500 mg/m(2)) (FEC75 therapy) and docetaxel (75 mg/m(2)) plus cyclophosphamide (600 mg/m(2)) (TC therapy) every three weeks as neoadjuvant or adjuvant chemotherapy was evaluated. Six or 9 patients received FEC75 or TC therapy, respectively. The nadir of white blood cells and neutrocyte counts in FEC75 and TC therapy were after 11-15 days and 8-11 days of chemotherapy, respectively. On the other hand, those of monocyte and reticulocyte counts were after 8-11 and 4-8 days for FEC75 and TC therapy, respectively. This suggests that there is a lag time in these parameters for the evaluation of myelosuppression in each chemotherapy regimen, resulting in the prediction of the degree of myelotoxicity by these profiles. Although 2 patients who received TC therapy encountered febrile neutropenia, the symptoms were improved by quinolones, and so granulocyte colony-stimulating factor was not needed. In addition, remarkable non-hematological side effects were not observed, and, therefore, almost all chemotherapy was performed as scheduled. From these results, FEC75 and TC therapy are considered to be safe.

[Assessment of chemotherapy-induced nausea and vomiting(CINV)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 cessation of treatments, antiemetic therapy has been thought important. Recently, the development of new antiemetic agents and the antiemetic guidelines provided by ASCO, NCCN, and MASCC etc. allow us to palliate CINV with appropriate antiemetic therapy. For appropriate antiemetic therapy, the patient must obtain accurate CINV information, particularly regarding whether it will be acute or delayed. MASCC first developed and posted the MASCC Antiemesis Tool (MAT) in 2004. The MAT is an eight-term scale for the assessment of acute and delayed nausea and vomiting, and is completed once per chemotherapy course. Although it is now validated in the US and UK and used worldwide, few reports have been available in Japan to use assessment tools including the MAT for acute and delayed CINV. We prospectively investigated the utility of the MAT. Fifteen ambulatory patients with breast cancer were subjected to evaluation, aged 29 to 73(median 58)years. In the results, the MAT allowed us to easily find patients treated with inappropriate antiemetic therapy. At the same time, it was easy to determine acute or delayed CINV, resulting in more appropriate treatment. The scale questions were unfamiliar to patients, but they clearly understood by means of a detailed explanation. Thus, it was suggested that the MAT is useful to assess antiemetic therapy. Consequently, it could contribute to completion of the chemotherapy.

[A case of paclitaxel-induced peripheral neuropathy successfully treated by H2-blocker, lafutidine].

We report a 75-year-old female gastric cancer patient with paclitaxel-induced peripheral neuropathy, which was successfully treated by the H2-blocker, lafutidine. From December 2007, she underwent second-line chemotherapy using paclitaxel (80 mg/m/2 day 1, 7, 14/28 days) for peritoneal dissemination which had been refractory to first-line chemotherapy using S-1 (80 mg/m / 2, day 1-28/42 days). After 2 courses, CT showed a complete response (CR) of the peritoneal dissemination. However, at the same time peripheral neuropathy appeared, which was aggravated to grade 3 at the 6th course. Beginning with the 7th course, we administered lafutidine (10 mg/day) for peripheral neuropathy, which recovered to grade 1 after 14 days of lafutidine administration. Lafutidine was administered until July 2008, when peripheral neuropathy kept grade 1 without lafutidine. After 9 courses, paclitaxel therapy failed because of general fatigue.

Synergistic action of statins and nitrogen-containing bisphosphonates in the development of rhabdomyolysis in L6 rat skeletal myoblasts.

OBJECTIVES: Nitrogen-containing bisphosphonates, which are widely used to treat osteoporosis, act as inhibitors of farnesyl pyrophosphate synthase, one of the key enzymes of the mevalonate pathway, and thus may have the potential to enhance the effect of statins (inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A reductase). In this study, we evaluated the synergistic effect of two nitrogen-containing bisphosphonates, alendronate and risedronate, in statin-induced apoptosis in rat skeletal L6 myoblasts. METHODS: L6 rat myoblasts were differentiated with drugs. DNA fragmentation was measured and small GTPase was detected by immunoblotting. KEY FINDINGS: Alendronate and risedronate caused dose-dependent apoptosis of L6 myoblasts. Risedronate induced detachment of rho GTPase from the cell membrane, followed by activation of the caspase-8-related cascade. Risedronate-induced apoptosis was synergistically enhanced with atorvastatin and significantly reduced by addition of geranylgeraniol. By contrast, alendronate did not reduce membrane GTPases and the apoptosis was caspase independent. CONCLUSIONS: These results suggest that risedronate-induced apoptosis is related to geranylgeranyl pyrophosphate depletion followed by rho detachment, whereas alendronate affects are independent of rho. Our results suggest a risk of synergistic action between nitrogen-containing bisphosphonates and statins in the development of rhabdomyolysis when treating osteoporosis in women with hyperlipidaemia.

[A case of bleeding tendency due to warfarin in a patient treated with chemotherapy by S-1].

A 82-year-old male patient had suffered from a cancer of the papilla of Vater. After the operation, he received 4 courses of gemcitabine(GEM)adjuvant chemotherapy and warfarin(WF)administration because of thrombosis in the left internal jugular vein. Since the tumors re-grew, GEM was discontinued, and chemotherapy including S-1 and GEM was examined. However, the chemotherapy could not be continued because of edema in both lower legs and tassel midway in the 2nd course. Because of a bleeding tendency(non-measurable INR(international normalized ratio of prothrombin time)), WF administration was discontinued on the 11th day after S-1/GEM combined therapy was suspended. On the following day, although the INR value recovered to 1.7, it gradually worsened and the symptoms of pulmonary embolism developed on the 13th day. Then, INR was controlled by continuous infusion of heparin. Since the INR level decreased after that, in addition to heparin, re-medication of WF was performed. We tried to analyze the genotype of a patient, who had a tendency to bleed by coadministration of WF with S-1, in terms of hepatic cytochrome P-450(CYP)2C9 and vitamin K epoxide reductase complex subunit 1(VKORC1). We also measured the plasma concentration of S-and R-WF by HPLC after obtaining informed consent from the patient. We found that he is homozygous for CYP2C9 1/1 and for A/A of VKORC1(-1639G>A). The obtained data did not show the abnormalities of blood coagulation. Because the genotype of a patient with a tendency to bleed was a major type in a Japanese population, fine monitoring of INR is required in order to prevent side effects of blood coagulation by S-1 and WF coadministration, regardless of patient genotypes.

[Management of hand-foot syndrome in patient treated with capecitabine].

Capecitabine is one of the most effective oral regimens of chemotherapy against advanced or recurrent breast cancer. In addition, capecitabine could widely be used for treatment of colon cancer. It appears that more patients will be administered capecitabine because of its QOL benefits. However, Hand-Foot Syndrome(HFS)may appear to be about 50% of the patients who take this regimen. As a result, the patient's QOL is hindered and led to a reduction of the dosage or discontinuation of the treatment depending on the grade of adverse event. This time, we evaluated the efficacy of topical emollients, creams and vitamin B6 for prevention and reduction of HFS symptoms for patients who received capecitabine. We found the efficacy of preventative measures that the occurrence of HFS grade 1 or above could be decreased and delayed. We also noticed that these preventative measures appear to be decreased the occurrence of HFS grade 2 or above, which led to a reduction of dosage or discontinuation of the treatment. For continuation and completion of the treatment and securing of patient's QOL, the supportive measures are needed to control a variety of side effects, such as HFS and others, and a team care support is indispensable.

[Induction of liaison-clinical pathway for patients with gastric cancer undergoing adjuvant chemotherapy using S-1 after curative gastrectomy].

The efficacy of adjuvant chemotherapy using S-1 for one year after curative surgical treatment for patients with gastric cancer of stage II or III was reported as the result of randomized controlled trial named ACTS-GC in 2007. Therefore the number of patients undergoing this adjuvant chemotherapy is predicted to be rapidly increasing in near future. On the other hand, the government promotes to construct the liaison-clinical pathway for patients with major carcinoma as a policy in 2007. According to these two backgrounds, liaison-clinical pathway for patients with gastric cancer undergoing adjuvant chemotherapy using S-1 after curative gastrectomy has been induced in our institute from November 2007. Not only alliance among doctors, nurses and pharmacologist in our institute but also communication with clinic is important to construct and manage this pathway. Three patients have been undergoing this pathway until now. All of them are satisfied with this pathway because of reliable feelings supported by intensive alliance between our institute and local clinic.

[Comparative survey on current status and the differences of treatment using modified FOLFOX6 regimen in patients with colorectal cancer in two general hospitals].

We surveyed the current status and the differences of treatment of colorectal cancer using modified FOLFOX6 regimen, in two general hospitals, Sakai City Hospital (A hospital) and Takarazuka Municipal Hospital (B hospital) between April 2005 and November 2006, retrospectively. The numbers of examined patients were 33 and 17 in A and B hospitals, respectively. The grade of myelosuppression and peripheral neuropathy were evaluated according to Common Terminology Criteria for Adverse Events v 3.0(CTCAE v 3.0)and Neurotoxicity Criteria of DEBIOPHARM(DEB-NTC). The setting of dosage was differed in two hospitals. In A hospital, the dosages of oxaliplatin, 5-FU bolus and 5-FU continuous infusion were more than 90% of the standard one at first time, and were reduced with almost same degree in the appearance of adverse effects. On the other hand, in B hospital, the dosages of these drugs were reduced about 20% even at first administration and, especially, the dose of 5-FU bolus tended to be remarkable reduction. Of adverse events, the rates of the appearance of neutropenia more than grade 3 was 21.2% and 47.1%, in A and B hospitals, respectively. No difference in peripheral neuropathy was detected at both hospitals. In conclusion, the differences in these two hospitals were detected in the dosage setting and myelosuppression, not in non-hematological adverse effects.

[Determining S-1 dosage at hospitals prioritizing cancer chemotherapy].

Although it is recommended that the standard S-1 dosage should be based on how large the body surface area is, an on-site setting of the appropriate dosage is often lower than the standard one, depending on the individual's condition and considering possible side effects and so, on. Here, we investigated usage conditions for S-1 as a part of field training for expert pharmacists at our hospital that performs total clinical treatments. Decreases in dosage per day for elderly patients were although the standard dosage is generally determined according to the amount of a patient's body surface. We conducted a retrospective survey with a total 90 patients by creating a tree-diagram to identify a reduction standard. It was found that the S-1 dosage was decreased when there were side effects, aggravation in performance status, decrease in kidney function, old age, combined injection chemotherapy, and a decrease in radiation therapy performance. The dosage decreases without such medical reasons were seen in only 4 of the 90 patients. The individual target dosage on the basis of daily medical examination.

[Equalization of spread of breast cancer chemotherapy regimen at general hospitals--with EC and FEC regimens].

We investigated the differences in safety and management of adverse events of chemotherapy among three hospitals, Sakai Municipal Hospital, Takarazuka Municipal Hospital and National Hospital Organization Osaka-minami Medical Center. The main purpose of this study was to equalize the spread of breast cancer chemotherapy regimen. The following three regimens were evaluated; epirubicin (75 mg/m(2)) /cyclophosphamide (500 mg/m(2)) (EC75), epirubicin (75 mg/m(2)) /cyclophosphamide (500 mg/m(2)) /5-fluorouracil (500 mg/m(2)) (FEC75) and epirubicin (100 mg/m(2)) / cyclophosphamide (500 mg/m(2)) /5-fluorouracil (500 mg/m(2)) (FEC100). Sixty-three patients were evaluated. We studied the level of myelosuppression after each regimen. As a result, there was no significant difference in neutrocyte counts at nadir after chemotherapy among hospitals and regimens. However, the values tended to be ranked EC75>FEC75>FEC100. In addition, we examined the risk of febrile neutropenia (FN) according to the multi- national association for supportive care in cancer (MASCC) scoring system. Almost all patients (61/63) were in the low risk group of FN, and only two patients had developed FN. At one hospital, patients receiving chemotherapy were prescribed ciprofloxacin tablets prophylactically for prexia over 38 deg C, and the patients learned from it. Thus, no marked difference in the safety (side effects such as myelosuppression) was recognized. However, management of side effects was different among these hospitals. In conclusion, it is very important to provide patients with adequate information on side effects.