Our aim was to clarify the side effects of irinotecan which occurred in patients admitted to Showa University Hospital to investigate whether the UGT1A1 genetic polymorphism status was reflected in the discontinuation or dose reduction of irinotecan. We retrospectively investigated UGT1A1 genetic polymorphisms, irinotecan dosage, dose discontinuance or reduction, and laboratory results from May 1 2009 to April 30 2010. The analysis of UGT1A1 genetic polymorphisms in 23 patients showed that frequencies of the UGT1A1*6 and UGT1A1*28 polymorphisms were 35% (eight patients) and 22% (five patients), respectively, and 17% (three patients) were UGT1A1*6/UGT1A1*28 compound heterozygotes. Of all patients who received irinotecan, dose reduction occurred in six patients (38%) and discontinuance in two patients (13%) due to neutropenia and other factors. Of these eight patients, seven (88%) had the UGT1A1*6 and/or *28 polymorphism. The most common irinotecan dose reduction was about 25% of the initial dose. Grade 4 neutropenia was observed in two patients who had the UGT1A1*6 and/or *28 mutation (13%), and one patient was a compound heterozygote. Our investigation confirmed that the UGT1A1 genetic polymorphism status of the patients was reflected in the discontinuance or dose reduction of irinotecan. Our results suggest that Grade 4 neutropenia may occur in patients who are compound heterozygotes and that these patients may need careful selection of treatment regimens possibly involving discontinuance or reduction in irinotecan dosage.

This paper presents a man in his 80's with pancreatic cancer(cStage IV). He suffered from nausea duringS -1 therapy, and therefore, prochlorperazine maleate at a daily dose of 15 mgwas administered. However, refractory nausea was diagnosed because it did not improve, and mirtazapine at a daily dose of 7. 5 mgbefore bedtime was started. Nausea was improved in the next morning, and the patient ate almost all of his breakfast. After that, no nausea appeared, and his food intake was robust. Mirtazapine is a new antidepressant called noradrenergic and specific serotonergic antidepressant(NaSSA)and blocks 5-HT3 receptors to improve nausea. Mirtazapine is usually started at a daily dose of 15 mg, but this dose induces somnolence. Therefore, mirtazapine was administered at a low daily dose of 7. 5 mgin the present case. No somnolence or disturbance of daily life was seen, and administration was safely continued. We conclude that low-dose mirtazapine is one effective option for refractory nausea duringS -1 therapy.

We set out to see if nutritional assessment(management)using MUST could be useful for patients undergoing outpatient chemotherapy.

The efficacy and safety of aprepitant(APR)were examined in cancer patients who received chemotherapy including cisplatin(CDDP)at a dose of ≥ 50mg/m2.APR was administered concomitantly with conventional antiemetic therapy to 20 patients(APR group)in a prospective study performed from May to July 2010. In addition, a retrospective study based on medical records of 20 patients(conventional therapy group)from February to April 2010 was performed.These patients received antiemetic therapy with a serotonin receptor antagonist and dexamethasone. Significantly more patients did not vomit in the 5-day study period(days 1-5).Also, severity of vomiting was significantly improved over the 5-day period and in the late phase(days 2-5)in the APR group, compared to the conventional therapy group. Loss of appetite was significantly improved over the 5-day period and the acute(day 1)and late phases, leading to increased food intake during the 5-day period and late phase. There were no adverse events with suspected involvement of APR, and the tolerability was favorable. These results suggest that APR is useful for nausea, vomiting, and appetite loss caused by CDDP, which is a highly emetic drug, and that such guideline-based antiemetic therapy might improve the quality of life of patients.

Bortezomib (Velcade(®)), a proteasome inhibitor, was launched for the treatment of relapsed or refractory multiple myeloma in Japan in December 2006. Prior to approval in Japan, high incidence (15.2%) and mortality (6.5%) of bortezomib therapy-related lung disorders were reported with private import treatment. Therefore the Velcade Lung Disorder Panel (the Panel) was established and the cases have been reviewed. A total of 3,556 patients, including 823 post-marketing surveillance (PMS) patients, have received bortezomib since April 25, 2009. The incidence of lung disorders associated with bortezomib therapy was 2.33% (3.77% in case of PMS). The panel reviewed the detailed information of 70 cases and classified the CT and X-ray images as follows: (1)Interstitial pneumonia; diffuse alveolar damage pattern, hypersensitivity pneumonia pattern and others (2)Vascular hyperpermiability; (non-cardiogenic) pulmonary edema pattern and capillary leak syndrome-like pattern (3)Hypoxia. These post-marketing data showed that the incidence of lung disorders in Japan was lower than expected based on private import data.

Assessment of renal function is important to determine the appropriate dose for cisplatin (CDDP)-based chemotherapy. Many previous CDDP-based chemotherapy trials for bladder cancer have required a creatinine-clearance (Ccr) ≧60 ml/min for entry. However, there is little evidence on renal function assessed by estimated glomerular filtration rate (eGFR) using the 4-variable Modification of Diet in Renal Disease Study Equation (MDRD), which has recently been introduced, to determine the eligibility for CDDP-based chemotherapy. To evaluate the proportion of patients with invasive urothelial carcinoma(UC) who would be ineligible ("unfit") to receive CDDP-based chemotherapy based on eGFR criteria (eGFR ＜60 ml/min/1.73 m2), and to determine the side effects of chemotherapy in these "unfit" patients, we conducted a retrospective clinical study. Our study population consisted of 61 consecutive patients who underwent 100% dose CDDP-based chemotherapy for invasive UC with 24 h-Ccr≧50 ml/min between June 2001 and July 2009. We assessed renal function using 3 equations (eGFR, Ccr according to Cockcroft-Gault formula (C-G Ccr), and Ccr examined by 24-hour urine collection (24 h-Ccr)) as well. Mean values of eGFR, C-G Ccr, and 24 h-Ccr were 58.6, 68.9, and 82.8 ml/min, respectively (P＜ 0.001). In total, 29/61(48%) patients were ineligible ("unfit") to receive chemotherapy based on eGFR criteria. However, there was no difference in the frequency of side effects between eGFR ≧60 ml/min/ 1.73 m2 and eGFR ＜60 ml/min/1.73 m2 groups. Our observations suggest that 24 h-Ccr≧50 ml/min would be a reasonable cutoff for CDDP-based chemotherapy even when eGFR ＜60 ml/min/1.73 m2.

We report here the experience of the treatment with sorafenib for advanced hepatocellular carcinoma (HCC) in our department. Forty patients received the therapy of sorafenib until April 2011. Twenty seven unresectable advanced HCC, 7 lung metastasis, 6 bone metastasis, 3 abdominal lymph node metastasis, and 2 peritoneal dissemination were included. The median duration of sorafenib treatment was 197 days. Grade 3 adverse event occurred in 9 patients (22.5%), and grade 4 adverse event occurred in 1 patient (3%). The response rate and disease control rate were 5% and 55%, respectively (CR 2, PR 0, SD 20, PD 9). The median overall survival was 15.2 months, and median recurrence-free survival was 3.7 months. These results suggested that a prevention of adverse events would lead to a continued treatment with sorafenib, and could expect to have a prolonged survival in patients with advanced HCC.

We report a case of GIST successfully treated with resection after a long-term control medication by molecular targeted drugs. A 59-year-old man underwent an un-complete resection for multiple abdominal tumors. The patient was treated with imatinib at a dose of 400 mg/day for high risk GIST. Since he had PD 22 months after the treatment, sunitinib was administered at a dose of 50 mg/day. However, abdominal tumor grew, and melena and intra-abdominal hemorrhage were appeared. After 27 months from the first treatment, a resection of tumors was performed to control abdominal hemorrhage. After the operation, abdominal tumor was successfully controlled with the treatment of imatinib.

We report a case of encephalopathy that was suspected to be caused by chemotherapy for liver metastasis from sigmoid colon cancer. A 72-year-old male was suspected that he had drug-induced eukoencephalopathy because he was presented with physical disorders during the FOLFOX/bevacizumab therapy. Although a brain MRI revealed Alzheimer disease, leukoencephalopathy was not excluded from the diagnoses due to a fact that his findings could not be compared before and after the chemotherapy. If leukoencephalopathy was suspected, chemotherapy should have been discontinued as soon as possible. Although a partial response was achieved, chemotherapy had to be discontinued in this case. The cases whose physical and neurological disorders were at risk due to a past history need an examination for nervous system in order to make a comparison with the findings before and after chemotherapy.

A 73-year-old man with advanced descending colon cancer and peritoneal metastases underwent a self-expandable metallic stent placement under fluoroscopic guidance on October 2007. The stent placement was successful without early complication. After 6 courses of FOLFOX4 followed by 7 courses of FOLFIRI, he received Bevacizumab-based chemotherapy from August 2008. In April 2009, he was admitted to our hospital with severe abdominal pain due to perforation of descending colon. Although emergent surgery was performed, he developed DIC and died on the 21 postoperative days. This case suggests that metallic stent placement for colorectal cancer cases might increase the risk of bowel perforation during Bevacizumab-based chemotherapy.

We have developed a pulmonary arterial infusion therapy for lung metastasis of colorectal cancer. Catheterization into pulmonary artery followed by occlusion with ballooning enabled the stasis of blood flow in the unilateral lung for 30 minutes. CDDP was infused via catheter to occluded pulmonary artery. Although no serious adverse events occurred in 5 cases, a tumor reduction in size was not observed. Loco-regional therapy for lung metastasis of colorectal cancer is limited because of recent progress of systemic therapy. However, a development of the procedure of pulmonary arterial infusion may enable a future success of local therapy for lung metastasis of colorectal cancer with a new drug, which is effective in such a short time disposure to tumor as 30 minutes.

As chemotherapy advances, patients who had liver metastases often come to receive liver resection after their chemotherapy, including oxaliplatin-based chemotherapy. We experienced a case of an acute hypersensitivity reaction to reintroduced-oxaliplatin at the second course of oxaliplatin-based adjuvant chemotherapy, after neoadjuvant chemotherapy for liver metastases originating from colon cancer. There is a report that hypersensitivity reactions are frequent in the second course of the reintroduced-oxaliplatin-based regimen. It is thought that the prevention is necessary at the second course even if there is no significant symptom at the first course. Similar cases will increase as neoadjuvant therapies spread in the future; therefore, prescriptions for preventing hypersensitivity are necessary when administering reintroduced-oxaliplatin base chemotherapy.

Hyponatremia is one of the major side effects that occurs after CDDP-based cancer chemotherapy. However, RSWS has rarely been reported as a cause of hyponatremia occurring after chemotherapy containing CDDP. A 70-year-old female who had recurrent lung adenocarcinoma after surgery was treated with CDDP, pemetrexed and bevacizumab-containing chemotherapy. She suffered from acute-onset consciousness disturbance and hyponatremia on day 3 of chemotherapy. Although SIADH was considered at the time of onset, the patient was subsequently diagnosed with RSWS, based on observations of dehydration, high levels of urinary sodium excretion and evidence of renal tubule failure. She recovered from these conditions without any residual disability after infusion of hypertonic saline fluid on day 13 of chemotherapy. In this report, we have described RSWS, which is rare complication that may follow CDDP-based chemotherapy. It is important, but not very easy, to distinguish between SIADH and RSWS clinically for the selection of an appropriate treatment.

Because it is considered that there is a close connection between gustation and olfactation, and that a decline in the function of either sensation influences the other one, it would be useful to clarify the relation between gustatory and olfactory disorders in patients receiving cancer chemotherapy. Therefore, we investigated the frequency of gustatory and olfactory disorders in patients administered anticancer drugs at the Division of Outpatient Chemotherapy of Kanazawa University. Among 136 patients who consented to participate in the investigation, 75 patients (55%) complained of a gustatory disorder, and 26 patients (19%) complained of an olfactory disorder. The occurrences of olfactory disorder were significantly greater in patients who had gustatory disorder than in patients who did not. The expression frequency of gustatory disorders was significantly higher among those taking docetaxel (85%) when compared with patients on other regimens. Although not statistically significant, the incidence of olfactory disorder was higher in patients taking docetaxel (31%), irinotecan+l-leucovorin (l-LV)+5-fluorouracil (5-FU) (31%), l-oxaliplatin+l-LV+5-FU (28%), trastuzumab (23%), and weekly paclitaxel (22%). Medical staff should recognize that olfactory disorders are similar to gustatory disorders, as they both have adverse reactions induced by anticancer drugs.