S-1/CDDP combination chemotherapy is conducted in many institutions, but most patients are hospitalized at the time of CDDP administration. We performed S-1/CDDP combination chemotherapy in 15 patients with advanced gastric cancer, and CDDP was administered in the outpatient department for 8 outpatients out of the 15 patients without renal failure or dysfunction. If outpatient chemotherapy can safely perform a regimen based on evidence, it brings about improvement in the QOL of the patient, and there are considerable advantages for economical care delivery. S-1/CDDP combination chemotherapy for outpatients was regarded as feasible with appropriate patient guidance.

Oral drug delivery is generally the most desirable means of administration, mainly because of patient acceptance, convenience in administration. Intestinal absorption mechanisms of anionic drugs have been mainly explained by the passive diffusion of nonionized compounds. However, several studies have suggested the involvement of specific transporters in intestinal absorption of weak acids including monocarboxylates. (-)-N-(trans-4-Isopropylcyclohexanecarbonyl)-D-phenylalanine (nateglinide) is a oral hypoglycemic agent possessing a carboxyl group and a peptide-type bond in its structure. Although nateglinide quickly reaches the maximal serum concentration after oral administration, nateglinide itself is not transported by PepT1 or MCT1. We demonstrated that nateglinide transport occurs via a single system that is H(+) dependent but is distinct from PepT1 or MCT1. In clinical, patients usually take many kinds of drugs at the same time. Thus, drug-drug interactions involving transporters can often directly affect the therapeutic safety and efficacy of many drugs. However, there have been few studies on food-drug interactions involving transporters. Dietary polyphenols have been widely assumed to be beneficial to human health. Polyphenols are commercially prepared and used as functional foods. We reported that ferulic acid, which is widely used as a functional food, affects the transport of clinical agents. The major dose-limiting toxicity after administration of irinotecan hydrochloride, 7-ethyl-10-(4-[1-piperidino]-1-piperidino)-carbonyloxycamptothecin (CPT-11) is severe diarrhea. We have found that a specific transport system mediates the uptake of active metabolite 7-ethyl-10-hydroxycamptothecin (SN-38) across the apical membrane in Caco-2 cells. Baicalin and sulfobromophthatlein inhibit this transporter. Inhibition of this transporter would be a useful means for reducing late-onset diarrhea.

Bone marrow suppression after intensive chemotherapies in patients with myeloid leukemia is severe, resulting in the reduction of the number of white blood cells, red blood cells, and platelets. Supportive therapies are indispensable for the management of these leukemia patients. The improvement of blood cell transfusion can decrease side effects of chemotherapies and establish the safety. But we still have notable side effects of transfusion such as TRALI (transfusion-related acute lung injury), platelet immunologic refractory state, and so on. Cytokine therapy especially with G-CSF (granulocyte colony-stimulating factor) administration, changed the treatment of myeloid leukemia. G-CSF can shorten the duration of neutropenia and decrease the risk of infection. Recently the effects of Epo (erythropoietin) on chemotherapy-induced anemia have been demonstrated. We discuss here the indications of blood cell transfusion and cytokine therapies in the treatment for myeloid leukemia.

A 78-year-old man was admitted for obstructive jaundice and unresectable bile duct cancer on March 4, 2008. Since biliary drainage was extremely difficult, he began 2 treatment courses of gemcitabine hydrochloride (GEM 800 mg/m(2) on days 1, 8, 15 every 4 weeks). He suffered from dry cough and dyspnea on May 13, 2008. He was diagnosed as GEM-induced interstitial pneumonia with severe hypoxemia by CT scan and arterial blood gas examination. He recovered with two courses of steroid pulse therapy, diuretics and antibiotics. Alternatively, he was given oral S-1 ( 80 mg/m(2) 4 weeks on and 2 weeks off) from June 12, 2008. His QOL was well kept without jaundice for as long as a half year. This is the first report of GEM-induced interstitial pneumonia in bile duct cancer. In conclusion, interstitial pneumonia must be taken into consideration as a rare adverse reaction when GEM is used for biliary neoplasms.

We retrospectively investigated the frequency and severity of adverse events in 124 patients with colorectal cancer who were treated by mFOLFOX6 regimen from August, 2005 to December, 2006. The incidences of grade 3/4 adverse events were; leucopenia 16%, neutropenia 40%, anemia 11%, thrombocytopenia 7%, febrile neutropenia 7%, nausea 3%, vomiting 2%, anorexia 2%, diarrhea 4%, fatigue 7%, and alopecia 0%. The incidences of all grades and grade 3/4 hypersensitivity reaction were 35% and 4%, and the median number of course when it firstly appeared was 6(range, 1-21). The incidences of all grade and grade 3 peripheral sensory neuropathy were 74% and 6%, and the median number of course when it firstly appeared 11(range, 6-16). The incidences of adverse events in this cohort were similar or lower than those reported in Western countries. Our investigation shows that mFOLFOX6 regimen is tolerable in clinical practice in Japan. The informed consent form was revised based on these results. The incidences of adverse events were renewed to provide useful information and improve self-care ability. The symptoms and the time to appearance of the hypersensitivity reaction and peripheral sensory neuropathy were added. We think it is important to provide the information based on the clinical practice.

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.

The efficacy of S-1 as part of a 2nd/3rd-line therapy in cases of advanced recurrent colon cancer was studied.

Recently, the significant efficacy of S-1 monotherapy or S-1 plus CDDP combination therapy has been reported. Docetaxel also has been reported to have favorable efficacy in gastric cancer. In addition, docetaxel can be administered in outpatient clinics. We investigated the efficacy and safety of S-1 plus docetaxel combination therapy for 35 naive patients with advanced gastric cancer. Docetaxel was administered at a dose of 40 mg/m(2) on day 1, and oral S-1 was administered at the full dose of 80 mg/m(2) twice daily for two weeks followed by one week rest. MST was 300 days, and the response rate was 42. 9%. Although leucopenia was observed in 31%, all patients were able to be continue this therapy. In conclusion, we considered that this S-1 plus docetaxel combination therapy was effective and safe in advanced gastric cancer, and convenient for outpatients.

The present retrospective study aimed to evaluate the anti-tumor activity and toxicity of combination chemotherapy with gemcitabine (GEM) and oral S-1 or UFT in patients with advanced or metastatic pancreatic cancer. Ninety-four patients received chemotherapy. Among them, sixty-three were treated with GEM alone, twenty-two with UFT and GEM (UFT/GEM), and nine with S-1 and GEM(S-1/GEM). The median survival time was 8.7 months with GEM, 7.3 months with UFT/GEM, and 23.3 months with S-1/GEM. The overall response rate was 11.1%, 10.0%, and 22.2%, respectively. The 1-year survival rate was 29.5%, 36.4%, and 85.7%, respectively. Although the treatment-related adverse effects were not infrequent in patients treated with S-1/GEM, they were moderate in intensity. The combination chemotherapy with S-1/GEM was well tolerated and yielded a high response rate in patients with pancreatic cancer.

The aim of this study was to evaluate retrospectively chemotherapy of weekly carboplatin and paclitaxel with concurrent radiation therapy for patients with locally advanced non-small cell lung cancer (NSCLC).

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.

A 72-year-old male with gastric cancer was referred to our hospital. The patient had been administered warfarin for cerebral infarction, aspirin and clopidogrel sulfate after percutaneous coronary intervention (PCI). Distal gastrectomy was performed for the lesion after discontinuing these drugs. After operation, warfarin was administered again as soon as possible, and on the other hand, we started treating the patient with S-1 for adjuvant chemotherapy carefully, because the interaction of each drug had been described before. On the sixth day after starting S-1, we reduced the amount of warfarin because PT-INR was elevated to a extremely high level of 6.84. Seven days later, PT-INR recovered to a slightly high level of 2.17. With continuation of S-1, PT-INR showed large fluctuations, so we needed to regulate the amount of warfarin carefully. It is important that we recognize the possibility of immediate interaction of two drugs and, before these drugs are administered, inform the patient about it.

SN-38, an active metabolite of irinotecan (CPT-11), is glucuronidated into SN-38G mainly by UGT1A1, during detoxification. However, significant interindividual pharmacokinetic variability in SN-38 is caused by factors, including inherited predispositions that may affect the function and expression of UGT1A1. Moreover, these individual differences can contribute to the development of clinical conditions, such as severe leucopenia and diarrhea. Similar to SN-38, bilirubin is excreted into bile after being glucuronidated by UGT1A1. Thus, bilirubin is metabolized by a mechanism similar to that of SN-38. This suggests that the bilirubin level may be an indicator of the adverse effects caused by CPT- 11. On the other hand, the ratio between the AUC of SN-38 and the AUC of SN-38G (AUCSN-38/AUCSN-38G) indicates the ability of SN-38 to be glucuronidated, and is known to correlate with leucopenia and diarrhea. However, many blood sampling points are required to calculate these AUCs. Therefore, the daily estimation of the AUCSN-38/AUCSN-38G values of individual patients is not practical at the clinical level. Thus, the objectives of this study were as follows: (1) to establish whether or not the total bilirubin level is a useful indicator in predicting the development of CPT-11 toxicity. (2) to investigate the correlation of SN-38/SN-38G (the ratio of the serum concentrations of SN-38 and SN-38G) with AUCSN-38/AUCSN-38G. Based on the result of this investigation, it will be discussed whether or not SN-38/SN-38G may be used as an alternative to AUCSN-38/AUCSN-38G. This study included 14 patients with small cell lung cancer or non-small-cell lung cancer, in whom serum concentrations of CPT-11, SN-38, and SN-38G were measured by HPLC. The results demonstrated a significant correlation between the total bilirubin levels prior to chemotherapy and the logarithmic values for AUCSN-38/AUCSN-38G (r2=0.852). Among the cases with high values for both the total bilirubin level and the AUCSN-38/AUCSN-38G ratio, none of the patients had grade-3 diarrhea, while many cases tended to have grade-3 to -4 neutropenia. Additionally, the results of regression analysis suggest that SN-38/SN-38G (2 hr) and SN-38/SN-38G (4 hr) might be preferable as a predictive index for AUCSN-38/AUCSN-38G. These findings suggest that the total bilirubin level and SN-38/SN-38G, 2 to 4 hours after administration might be used as indicators to predict CPT-11-induced neutropenia. These indicators are likely to contribute to the pharmacogenetic analysis of UGT1A1 genes, as well as individualized therapy, in future, and further studies on this subject are expected.

We set out to determine the efficacy of indisetron hydrochloride for the management of chemotherapy-induced nausea and vomiting including carboplatin for lung cancer. Indisetron hydrochloride was given orally to 32 patients (indisetron group), and intravenous 5-HT3 receptor antagonists were given to 24 patients (control group). The number of patients with nausea or vomiting occurring within 24 hours and 24 to 72 hours after chemotherapy was measured. The complete inhibition of the vomiting within 24 hours after chemotherapy was 100% in the indisetron group and 95.8% in the control group. Twenty-four to 72 hours after chemotherapy, the complete inhibition of vomiting rate was 97.1% and 95.8%, respectively. In addition, the complete inhibition of nausea rate within 24 hours after chemotherapy was 87.5% in the indisetron group and that was 95.8% in the control group. The complete inhibition of nausea rate 24 to 72 hours after chemotherapy was 56.3% and 70.8%, respectively. No serious adverse events were observed. The comparison of the efficacy between the indisetron group and control groups did not reach statistical significance (p> 0.05). These findings suggest that prophylactic administration of indisetron hydrochloride is useful for the inhibition of acute and delayed nausea and vomiting caused by chemotherapy in lung cancer patients.

Recently, some new anticancer agents and hormonal agents can be used to treat breast cancer, and more patients are administering combinations of these drugs in clinical practice. Tegafur and Uracil (UFT) have been widely used for the postoperative chemotherapy of breast cancer, and often combined with hormonal agents. However, due consideration has not been given to safety and compliance of the combined use of UFT and aromatase inhibitor (AI). We therefore studied the safety and compliance with UFT alone and in combination with the hormonal agents tamoxifen or anastrozole as postoperative therapy in postmenopausal women with breast cancer. Our results confirmed that longterm postoperative therapy with UFT alone was feasible, provided that early adverse events are carefully monitored. Combined therapy was not associated with a significant increase in the incidence of adverse events or a decrease in compliance, even in older adult patients. Therefore, we consider UFT plus a hormonal agent (especially anastrozole) to be a treatment option for patients with HER2-negative highly or incompletely endocrine responsive disease who require relatively moderate chemotherapy or for older adult patients who require treatment with low toxicity.

Recently, aromatase inhibitors (AI) are widely used in postoperative adjuvant therapy for breast cancer. Nevertheless, studies of postoperative therapeutic strategies for recurrent breast cancer are insufficient.