A 67-year-old woman was diagnosed with chronic lymphocytic leukemia (CLL) in October 2001. In August 2004, she received chemotherapy consisting of fludarabine and cyclophosphamide (FC therapy). After three cycles of FC therapy, the number of tumor cells was markedly decreased. However, anemia progressed. She was diagnosed with pure red cell aplasia (PRCA) by bone marrow examination and was successfully treated with cyclosporin A (CsA). In October 2008, anemia progressed with the exacerbation of CLL and she received three cycles of fludarabine therapy. Although the number of tumor cells diminished, the anemia did not improve. She was diagnosed with PRCA recurrence and was again successfully treated with CsA. PRCA is a rare complication in patients with CLL and has been attributed to T cell-mediated mechanisms. Six cases with PRCA that developed after fludarabine therapy for CLL have already been reported. Fludarabine therapy may be toxic to Treg, resulting in the loss of self-tolerance. It is important to consider the possibility of PRCA in patients with progressive anemia after fludarabine therapy for CLL.

Chemotherapy-induced oral mucositis (CIOM) is a severe adverse event resulting from cancer chemotherapy. Toxic free radicals and pro-inflammatory cytokines produced by anticancer drugs have been reported to be associated with CIOM. Rebamipide has been shown to increase gastric endogenous prostaglandin E2 and I2, to promote gastric epithelial mucin, and to behave as an oxygen free-radical scavenger in addition to other anti-inflammatory actions. We developed a gargle solution of rebamipide, adding ultrahydrogel for mucosal protection and to maintain rebamipide on the oral mucosa. A 300 mL rebamipide gargle solution combines 600 mg rebamipide, 3 g high molecular-weight polyethylene oxide, 1.2 g carrageenan, pineapple flavoring, and water. The efficacy of the rebamipide gargle was evaluated in 175 patients with CIOM from November 2009 to December 2012, each instructed to use the rebamipide gargle 5-6 times daily. The severity of CIOM was assessed according to the National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE, version 4.0). Their CTCAE scores (3/2/1/0) changed from n=13/64/98/0 to 0/10/103/62, respectively, after initiation of the rebamipide gargle (p<0.01; paired t-test). The median duration to best response was 14 days (range: 1-49). CTCAE scores decreased in 132 patients (75.4%), including 62 (35.4%) who achieved grade 0. There were no unexpected safety events. Rebamipide gargle was well tolerated and demonstrated to have significant therapeutic efficacy against CIOM.

Severe stomatitis caused by chemotherapy and radiotherapy is accompanied by severe pain and results in a poor quality of life. We used a spray preparation of indomethacin (IM; 0.25% IM dissolved in phosphate buffer, pH 7.4), a nonsteroidal anti-inflammatory drug (NSAID) to control the pain associated with stomatitis at the University of Tsukuba Hospital. This review specifically aimed to collect information on the use of the IM spray preparation, from our previous studies, to facilitate its proper use in a hospital setting. On studying the stability of the IM spray preparation, we concluded that the preparation should be kept in the refrigerator for daily use, and that it can be stored for at least 2 months at 4°C, and for 24 months at -20°C. To evaluate the efficacy of the IM spray preparation, we retrospectively surveyed its analgesic effects. Using the 10-grade Visual Analogue Scale in 23 patients, we found that pain associated with stomatitis was reduced from 10 to 4.7 after application of the spray. In conclusion, our study results on the stability and efficacy of the IM spray preparation have led to the proper use of the spray in cancer patients with stomatitis caused by chemotherapy and radiotherapy.

We report a case of a 56-year-old woman admitted to our hospital for status epilepticus. Three months before hospitalization, the patient underwent gross total removal of a glioblastoma with BCNU wafer implantation in the left parietal lobe. The cavity was subsequently lined with five BCNU wafers. After admission, magnetic resonance imaging(MRI)showed cyst formation accompanied by strong edema, with no recurrence of glioblastoma. She was initially administered antiepileptic drugs and glycerol with betamethasone, after which her seizures stopped but recurred one month later due to a decrease in betamethasone. The BCNU wafers were removed four months after the initial surgery, after which the seizures completely stopped. Histopathological examination of the cavity indicated the presence of inflamed tissue and no recurrence of glioblastoma. Neurosurgeons should be aware of the possibility of cyst formation after BCNU wafer implantation for malignant gliomas. In this manuscript, we provide a case presentation and a review of the literature.

Guidelines for antiemetic therapy, such as the American Society of Clinical Oncology (ASCO) guidelines, recommend that aprepitant, an NK1 receptor antagonist, should be used in addition to conventional antiemetic therapy for acute and delayed nausea/vomiting caused by highly emetogenic chemotherapy. However, only few studies have been conducted to evaluate the efficacy of aprepitant in patients receiving moderately emetogenic chemotherapy. Therefore, we examined the antiemetic effects of additional doses of aprepitant in the next course in patients with lung cancer who were undergoing chemotherapy with carboplatin and who developed chemotherapy-induced nausea and vomiting (CINV) despite the preventive administration of a 5-HT3 receptor antagonist and dexamethasone. Consequently, the incidences of vomiting and nausea significantly decreased from 59% to 0% and from 91% to 64%, respectively, during the entire study period. Furthermore, a significant improvement in dietary intake during the entire study period was confirmed. These results suggest that the additional administration of aprepitant has high antiemetic effects in patients with lung cancer who are undergoing chemotherapy with carbo- platin and who show insufficient control of nausea/vomiting.

Toxicity and efficacy of pemetrexed monotherapy in advanced non-small-cell lung cancer patients with impaired renal function treated between May 2009 and May 2012 at Gifu University Hospital were retrospectively analyzed. A total of 10 and 17 patients had a creatinine clearance rate (Ccr) of <45 mL/min and ≥45 mL/min, respectively. The median age was higher in the Ccr<45 mL/min group (78.9 years) than in the ≥45 mL/min group (65.2 years). The rate of neutropenia above Grade 3 was 30% in the Ccr<45 mL/min group and 6% in the ≥45 mL/min group. Therefore, reducing the dose of pemetrexed should be considered in patients with impaired renal function. Non-hematologic toxicities were not correlated with the renal function. There was no treatment-related death, and most of the toxicities were mild and tolerable. Stable disease was observed in 6 patients (60%) in the Ccr<45 mL/min group, and in 12 patients (70%) in the Ccr≥45 mL/min group, although some patients in both groups showed neither complete nor partial responses. The disease control rate and median progression-free survival time were 60% and 2.8 months in the Ccr<45 mL/min group, and 70% and 2.9 months in the Ccr≥45 mL/min group, respectively. Thus, in this analysis, treatment with pemetrexed resulted in clinically equivalent efficacy in advanced non-small-cell lung cancer patients regardless of the state of renal function.

We investigated the relationship between vascular pain and various characteristics (age, sex, cancer stage, performance status [PS], height, weight, body mass index [BMI], body surface area, oxaliplatin dose, and presence and absence of the initial administration of dexamethasone) in colorectal cancer patients who were administered initial doses of oxaliplatin intravenously. The study population included 29 patients treated at Higashi Totsuka Memorial Hospital between June 2010 and April 2014. One-way analysis of variance showed that vascular pain was significantly associated with weight (p=0.015), body surface area (p=0.013), and oxaliplatin doses (p=0.0026), where the significance level was p=0.05. Logistic regression analysis and the likelihood ratio test demonstrated that the likelihood of vascular pain increased with the increase in the oxaliplatin dose. According to the cut-off value of vascular pain determined using the receiver operating characteristic (ROC) analysis, a single dose of oxaliplatin was determined to be 175 mg or more. According to the cut-off value established using the ROC analysis, a single dose of oxaliplatin at which vascular pain is expressed was determined to be 175 mg or more. At this dose, 13 patients complained of vascular pain and 8 did not. At doses less than 175 mg, none of the 8 patients complained of vascular pain. These results suggest that lowering the diluted concentration and reducing the infusion rate of intravenously administered oxaliplatin may reduce vascular pain.

A 53-year-old patient with recurrent ovarian clear cell adenocarcinoma developed fever (39°C) and cough on day 28 of liposomal doxorubicin chemotherapy, the 4th cycle of the 4th regimen since initial treatment. Drug-induced interstitial pneumonia was suspected from a chest CT image showing diffuse ground-glass opacities; however, we deduced pneumocystis pneumonia from the elevated serum beta-D-glucan levels. After effective treatment with sulfamethoxazole and amphotericin B, the patient's symptoms and radiological findings improved. Pneumocystis pneumonia is an opportunistic infection that poses a risk not only for patients undergoing aggressive immunosuppressive therapy, those infected with HIV, and those with transplants, but also for patients undergoing chemotherapy. When pneumonia is diagnosed during chemotherapy, it is essential to consider the possibility of pneumocystis pneumonia.

Pneumatosis cystoides intestinalis (PCI) is a relatively rare condition, characterized by subserosal or submucosal air within the bowel wall. Herein, we report a rare case of PCI secondary to treatment with an epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI). A 71-year-old man, who had received gefitinib therapy for 2 years and 5 months for lung adenocarcinoma with metastases to the bones and brain, presented with abdominal pain, diarrhea, and vomiting. Computed tomography of the abdomen revealed intramural air in the small bowel, free air in the abdomen, and moderate ascites. A diagnosis of PCI was made, and the patient was managed conservatively by discontinuing gefitinib treatment, because his vital signs were stable and there was no sign of peritonitis. The patient's symptoms gradually improved, and follow-up CT after 1 week revealed that the initial findings had almost completely resolved. Clinicians should note that treatment with gefitinib might cause PCI.

Cisplatin (CDDP) is a key drug in the systemic treatment of various solid tumors. Brand-name CDDP may differ across generic formulations considering various clinical parameters. Therefore, in this study, we aimed to assess the safety of a generic CDDP formulation. To compare brand-name CDDP with a generic formulation, the incidence of adverse events, especially renal toxicity, was investigated in 500 patients with thoracic malignancies who received chemotherapy with more than 60 mg/m2 of either brand-name or generic CDDP. We compared the maximum serum creatinine (Cr) level after chemotherapy in the 2 groups. The correlation coefficients between the pretreatment Cr and the maximum Cr after CDDP administration did not differ between brand-name CDDP and generic CDDP (0.610 and 0.644, respectively; p=0.528). Furthermore, the correlation coefficients did not differ in subgroup analysis according to sex or adjuvant therapy. The severity of adverse events was similar in the 2 groups. In conclusion, generic CDDP can safely be used as an alternative to brand-name CDDP in the clinical setting.

Nogitecan hydrochloride(topotecan)has shown efficacy in patients with recurrent ovarian cancer, but has not been used widely in Japan. We evaluated the efficacy and adverse effects of topotecan in 12 patients (median age, 62 years) treated for recurrent ovarian cancer between 2000 and 2013. Four patients had relapsed after primary treatment, and 8 had relapsed at least twice. Seven patients had been treated with more than 3 prior regimens. Initial treatment of the 12 patients consisted of intravenous topotecan (1.0-1.4 mg/m2/day) for 5 consecutive days. Initial doses were based on previous chemotherapy and/ or renal function, with reduced doses administered to patients with severe adverse effects during prior courses of treatment. The 12 patients received a total of 54 courses of topotecan(range, 1-15 courses). Of these 12 patients, one achieved a partial response and 6 had stable disease. The median time to progression was 14.4 weeks. All 12 patients had grade 3-4 myelosuppression, while none had febrile neutropenia or severe non-hematologic toxicities. Patients who received higher doses or increased courses of chemotherapy had apparently more severe adverse events. These findings suggested that topotecan should be used as a second- or third-line treatment, rather than later, in patients with tumor recurrence, with its dose reduced according to the physical status of each patient. Such strategies may enhance both the efficacy and safety of topotecan in patients with recurrent ovarian cancer.

In Japan, patients with malignant glioma have been treated with BCNU wafers (Gliadel®) since January 2013. Several adverse events(AEs)associated with implantation of BCNU wafers, including cerebral edema or cyst formation, are recognized. Here, we report a retrospective review of the experience with implantation of BCNU wafers in our institutions and our findings regarding the risk factors for the AEs.

We examined the usefulness of measurement of procalcitonin (PCT) for patients, who developed febrile neutropenia during cancer chemotherapy for urological cancer. Of the Patients who underwent cancer chemotherapy for bladder, renal pelvic or ureteral, and testicular cancer in our department from 2010 to 2013, 51 had febrile events. Their clinical courses and PCT values were retrospectively reviewed and analyzed. PCT was positive in 12 patients and negative in 39. The duration with febrile status was significantly longer in the PCT-positive group than in the PCT-negative group. There was no significant difference between the blood count values in each group, but C-reactive protein (CRP) was significantly higher in the PCT-positive group than in the PCT-negative group. There were no significant differences between the 2 groups in other tests with blood. There were 12 patients with febrile neutropenia (FN) but all were classified into low-risk by the MASCC scoring system. Four of these 12 patients were positive for PCT. Our results suggested that, in patients with a fever of 37.5°C or more during the course of cancer chemotherapy for urologic cancer, bacteremia possibly existed if the patient was positive for PCT. In addition, the duration of fever tended to be longer and the condition was more severe. When the patients with urological cancer undergo cancer chemotherapy manifest high-grade fever, PCT is promising and valuable as an indicator of the severity of infection.

A 64-year-old man with central nervous system metastases from systemic non-Hodgkin lymphoma was treated with high- dose intravenous methotrexate(MTX 3.5 g/m2). The patient subsequently developed oliguric acute renal failure 12 hours after MTX initiation, and his serum MTX level was 163 mM at 26 hours. Hemodialysis filtration(HDF)combined with direct hemoperfusion(DHP)was initiated at 45hours. Seven sessions of combined HDF and DHP and 2 courses of HDF alone were performed, and the mean MTX extraction rates were 68.2% and 74.3%, respectively. The patient experienced severe respiratory failure, febrile neutropenia, myelosuppression, and oral mucositis. However, his urine output began to improve on day 7 after MTX initiation, and his renal function gradually recovered. His serum MTX level declined to 0.04 mM on day 23 after MTX initiation. In the present case, we immediately initiated HDF and DHP and successfully treated the patient for MTX-induced renal failure.

A drug use results survey for the TS-1(R)capsule was conducted on patients with non-small cell lung cancer. A total of 1,784 patients were registered for the survey, 1,669 of whomwere evaluated for safety. The incidence of adverse drug reactions was 67.9%(1,134/1,669). The overall incidence of interstitial pneumonia was 1.38%(23/1,669), while it was 1.34% in patients treated with TS-1(R) alone(14/1,046). The risk factors for interstitial pneumonia according to this survey included allergic predisposition, concomitant diseases(including interstitial pneumonia), past medical history(including interstitial pneumonia), and combination with anticancer drugs(excluding cisplatin). Among the spontaneous reports of interstitial pneumonia as an adverse drug reaction from physicians, test images were available in 39 cases. These images were analyzed by the Safety Review Committee for interstitial pneumonia, consisting of external medical experts. In addition, the imaging patterns, settings of occurrence, and patient's backgrounds were reviewed. Twenty-five of the 39 cases were assessed to be possible interstitial pneumonia, of which 10 were confirmed to have an imaging pattern of diffuse alveolar damage. Based on the above findings, it is essential to check the patient's medical history for conditions such as lung disorder through a medical interview and an imaging test, prior to starting treatment with TS-1(R).

Irinotecan is an effective drug in the treatment of colorectal cancer. However, there are reports of an association between certain UGT1A1 genetic polymorphisms and the development of adverse reactions(such as neutropenia)related to irinotecan metabolism. We retrospectively investigated UGT1A1 genetic polymorphisms and the occurrences of irinotecan-induced neutropenia in 25 patients of colorectal cancer at our hospital. Analysis of UGT1A1 genetic polymorphisms in these patients yielded the following classifications: a wild-type group( *1/*1)comprising 13 patients(52%), a heterozygous group(*1/ *28, *1/*6)of 10 patients(40%), and a homozygous group(*28/*28, *6/*6)of 2 patients(8%). The frequency of neutropenia was 15.4%(2/13)in the wild-type group, 30%(3/10)in the heterozygous group, and 100%(2/2)in the homozygous group. Grade 4 neutropenia only occurred in the homozygous group. These results suggest that a dose reduction of irinotecan should be considered for patients who fall into the homozygous group upon analysis of their UGT1A1 genetic polymorphisms, as such patients might be susceptible to grade 4 neutropenia.

Afatinib is an epidermal growth factor receptor-tyrosine kinase inhibitor(EGFR-TKI). In a randomized phase III study(Lux- Lung 3 study)employing patients harboring EGFR mutations, patients administered afatinib show a significantly longer progression free survival time(PFS)than those administeredcombination chemotherapy comprising cisplatin andpemetrexed . However, most of the patients(95.2%)treatedwith afatinib experiencedd iarrhea. In the present report, 16 patients with EGFR mutations were treatedby afatinib at our institution from May 2014 to December 2014. Twelve patients were administered a diarrhea prevention herbal medicine, Hange-shashin-to. Seven of 12 patients(58%)had no diarrhea during the 28 days of therapy. All 4 of the patients who did not receive Hange-shashin-to experienced diarrhea above Grade 1 within 6 days of starting therapy. The rate of diarrhea differed significantly between the patients receiving and not receiving Hangeshashin- to. In conclusion, preventive administration of Hange-shashin-to may reduce the occurrence of diarrhea during afatinib treatment.