The use of new agents (NAs) such as bortezomib, thalidomide, and lenalidomide has extended the survival of patients with multiple myeloma (MM). However, whether long-term treatment using NAs may increase the risk of second primary malignancies is a concern. Three hundred and thirty-three patients with MM were treated at our hospital from 1998 to 2013. Additional chromosomal abnormalities (CAs), associated with secondary myelodysplastic syndrome/acute myeloid leukemia, were observed in 13 of 152 users of NAs, but in 38 of 181 non-users of NAs. The cumulative CA incidence was higher in non-users of NAs. The CAs frequently observed were 13q-, 20q-, +8 in users of NAs, while -5/5q- and -7/7q- were detected in non-users of NAs. The total dose and treatment period of NAs did not differ between CAs-positive and -negative patients. However, a higher dose of melphalan was observed to have been used in patients who had CAs. Longer follow-up periods are necessary for an accurate risk assessment.

A 78-year-old man was diagnosed as having right renal cell carcinoma (RCC) with metastasis to the right lung. He received sunitinib and the treatment reduced the size of both RCC and lung metastasis. Then he received right radical nephrectomy. The pathological diagnosis was clear cell RCC. After the initial surgery, he was diagnosed with polymyalgia rheumatic and steroid therapy was started. During follow-up, local recurrence was discovered and sunitinib was then started at a dose of 25 mg/day. Two months after the treatment, abdominal computed tomography (CT) revealed colonic pneumatosis cystoides intestinalis. Administration of sunitinib was stopped and the patient was observed carefully without pursuing surgical intervention. A follow-up CT demonstrated resolution of the colonic pnumatosis.

Hepatitis B virus(HBV)reactivation has been reported as a fatal complication following systemic chemotherapy or other immunosuppressive therapies. The Japanese Guidelines for HBV reactivation were published in 2009. Despite the publication of these guidelines, there have been some reports of fulminant hepatitis B. Therefore, it was suggested that the guidelines were not yet been widely implemented. We investigated whether the guidelines had been implemented in our hospital. After the evaluation, it was determined that 89%of HBV cases were screened for the HBV surface antigen(HBs-Ag). Additionally, the screening for HBV surface antibody(HBs-Ab)and HBV core antibody(HBc-Ab)should be performed in cases negative for HBs-Ag, which was performed in only 17% of HBs-Ag-negative cases. It was concluded that the guidelines had not been implemented in our hospital. Therefore, we conducted educational activities to promote the implementation of the guidelines. Screening tests were performed in all 270 HBV cases between January and June 2013. Two antigen-positive carriers were identified. The rate of HBs-Ag-negative and/or HBc antibody -positive cases was 20.3%. Of these, 76.4%were tested using a DNA quantitative test, but DNA quantification did not increase in any case. HBV reactivation is expected to increase due to the development of new drugs and the use of diverse regimens. All physicians who perform immunotherapy and chemotherapy should immediately participate in educational activities.

Gefitinib anderlotinib, which are epidermal growth factor receptor(EGFR)tyrosine kinase inhibitors(TKIs), have been usedfor the treatment of inoperable andrecurrent non-small cell lung cancer(NSCLC)patients. These drugs are known to cause a skin rash, one of the major side effects, at a high frequency. Biotin is a water-soluble vitamin, andit belongs to the vitamin B family. It is well known that biotin deficiency increases the risk of skin dermatitis. We administered biotin to four patients with skin rash, all of whom were treatedwith either gefitinib or erlotinib andwere unable to be treatedby a steroid ointment alone. In all patients, administration of biotin reduced the skin rash. Surprisingly, in 2 patients in whom EGFR-TKI therapy was discontinued because of the skin rash, the administration of biotin allowed for long-term gefitinib or erlotinib treatment. Biotin may be considereduseful for the treatment of skin rash causedby EGFR-TKIs. Further trials may be needed to confirm the value of biotin in this setting.

The safety and effectiveness of pemetrexed(PEM)in patients with non-small cell lung cancer(NSCLC)were reviewed using data from post-marketing surveillance. Among 699 patients registered from June 2009 to May 2010, 683 patients were analyzed(343, first-line therapy: 340, second-line therapy or beyond). Patient backgrounds were as follows: median age=65 years(16.1%B75 years old); 64.7% male; 91.9% performance status 0-1; 83.2% Stage IV; 99.0% non-squamous cell cancer. Also, 86% of the first-line and 20% of the second-line cohort were receiving a concomitant anti-cancer drug(mostly platinum agents). The incidence rate of adverse drug reactions(ADR)was 76.7%, including serious cases(18.0%). The most common ADRs were decreased white blood cell count(26.8%), decreased neutrophil count(25.3%), anemia(19.2%), decreased platelet count(17.0%), and nausea(23.0%). The incidence of interstitial lung disease, which is a concern during chemotherapy, was 2.6%. Peripheral neuropathy and alopecia, events influencing a patient's quality of life, were less than 1%. The estimated median survival time was 23.2 months[95%CI: 19.8 months-not calculable]in the first-line cohort, and 11.8 months[95% CI: 10.5-13.7 months]in the B second-line cohort. The surveillance results showed no apparent difference in total ADRs in this current study compared to the safety profile established in clinical trials previously conducted in Japan and overseas. These results demonstrate the safety and effectiveness of PEM treatment for NSCLC patients in daily clinical settings.

Cancer chemotherapy-induced anemia(CIA)is observed in approximately 70%of patients treated with cytotoxic chemo- therapy. The hemoglobin concentration in the peripheral blood is C10 g/dL in 40% of these patients, and C8 g/dL in 23% of these patients. Red blood cell transfusion is performed in 16% of these patients. Since erythropoiesis-stimulating agents (ESA)are not approved in Japan, blood transfusion is the only choice of treatment for CIA. In Northwestern countries, ESA have been utilized for the treatment of CIA for >20 years. Recently, however, the use of ESA has become regulated towing to concerns about the potential life-shortening effects, although ESA are still the treatment of choice for CIA. In this paper, the characteristics of CIA in Japan and the underlying issues have been discussed.

The Japan Society of Clinical Oncology and The Japan Society of Transfusion Medicine and Cell Therapy jointly conducted a questionnaire-based survey on chemotherapy-induced anemia(CIA)in cancer patients between September and November 2010, the results of which are outlined here. For all the eight main cancer types in Japan that were analyzed(breast, lung, stomach, colorectal, liver, gynecologic, and urologic cancers and malignant lymphoma), blood transfusion was required in 1.6-24.0%(mean=7.5%)of patients who received chemotherapy, and 3.9-7.3 units(mean=5.9 units)red blood cells were transfused per patient. Approximately 146,000 units of red blood cells, accounting for 2.2%of the total annual supply of red blood cell products, was estimated to be transfused to cancer patients with CIA every year. In addition, approximately 172,000 cancer patients with CIA, accounting for 40% of patients receiving chemotherapy, were estimated to have hemoglobin(Hb)levels below 10 g/dL annually. In patients who received red blood cell transfusions, the average Hb level prior to chemotherapy was 9.5 g/dL and the average lowest Hb level after starting chemotherapy was 6.9 g/dL; these values were 11.6 g/dL and 10.4 g/dL, respectively, in patients who did not receive transfusion. Furthermore, for all cancer types, almost no red blood cell transfusions were performed in patients with an Hb level of 8.0 g/dL or higher, although many patients with an Hb level of 6.9 g/dL or lower also did not receive red blood cell transfusions. These results highlight the strict restriction of red blood cell transfusion to cancer patients with CIA. Therefore, the use of alternative therapies such as erythropoiesis-stimulating agents should be considered to improve the quality of life of cancer patients with CIA.

The prognosis of cancer patients with anemia is poor. In Japan, these patients are treated only with red blood cell transfusions, and doctors cannot use erythropoiesis stimulating agents(ESAs)such as epoetin and darbepoetin. On the other hand, ESAs are widely used in the USA and Europe to treat patients with chemotherapy-induced anemia. However, the results of randomized controlled trials(RCTs)and meta-analysis have suggested that the use of ESAs was correlated with increasing incidence of venous thromboembolism(VTE)and mortality. The American Society of Clinical Oncology(ASCO)and the American Society of Hematology(ASH)guidelines, revised in 2010, recommend the minimal use of ESAs for patients with chemotherapy-induced anemia, except for anemic cancer patients who are not currently receiving chemotherapy. A change in the target hemoglobin(Hb)level to achieve a concentration of 12 g/dL was recommended in 2007 as the lowest concentration required to avoid transfusions. We discuss the cause of anemia in cancer patients, and examine the current state of the clinical use and problems associated with ESAs.

Although recent advances in chemotherapy have led to improved quality of life(QOL)and prolonged survival in patients with advanced cancer, treatment is often discontinued because of adverse events associated with chemotherapy, regardless of its efficacy.Nevertheless, chemotherapy has been validated in the United States and United Kingdom and is used worldwide. In Japan, few reports have been published regarding the use of assessment tools including the Multinational Association of Supportive Care in Cancer(MASCC)Antiemesis Tool(MAT)for the evaluation of chemotherapy-induced nausea and vomiting(CINV).We prospectively investigated the utility of the MAT and digestive symptom diary(DSD).In total, 68 patients who underwent highly and moderately emetogenic chemotherapy were included in the efficacy analyses.The improvement in the control of CINV during the delayed phase was significantly different between the DSD and MAT groups(p= 0.0148).The results obtained using the MAT warrant further validation.Meanwhile, the DSD may be used as an information tool by medical staff and patients.

We evaluated the effect of using the cooling method on pain at the site of luteinizing hormone-releasing hormone(LH-RH) agonist injection in 181 prostate cancer or premenopausal breast cancer patients by using a numerical rating scale(NRS)and a questionnaire survey with open-ended questions. According to the NRS, 38.1% of the patients experienced a reduction in pain, 37.5% experienced no change, and 24.4% experienced an increase in pain. Therefore, use of the cooling method did not have a statistically significant effect in terms of pain reduction(p=0.123). However, on analyzing pain reduction according to the answers in the questionnaire survey, 53.2% of the patients experienced a reduction in pain, 38.5% experienced no change, and 8.3% experienced an increase in pain. These findings were different from those obtained on using the NRS. In addition, irrespective of using the cooling method, needle thickness and patient obesity strongly influenced the pain experienced. The skin icing method was effective in reducing pain at the site of LH-RH agonist injection. This method is simple, inexpensive, and safe, and is hence recommended.

We investigated the therapeutic effects and safety of fine powder cisplatin for patients with advanced hepatocellular carcinoma( HCC). From January 2006 to March 2012, 123 patients with advanced HCC were treated by transarterial infusion chemotherapy(TAI)with fine-powder cisplatin(IA-call®, Nippon Kayaku Co. Ltd., Tokyo, Japan). The drug was infused into the liver through the feeding artery at a dose of 65 mg/m2. The treatment was repeated every 4 to 8 weeks until evidence of either tumor progression or unacceptable toxicity appeared. Treatment responses were classified as complete response(CR), partial response(PR), stable disease(SD), and progressive disease(PD)in 3.2%, 12.0%, 32.2%, and 52.4% of patients, respectively. The median survival durations were as follows: overall, 12.2 months; CR/PR patients, 23.8 months; and SD/PD patients, 10.6 months. The cumulative survival rates of CR/PR patients were significantly higher than those of SD/PD patients (p<0.05). Multivariate analyses revealed that treatment response, etiology, Child-Pugh grading, and level of protein induced by the vitamin K antagonist- II (PIVKA- II )were predictive factors of survival duration. Problematic adverse events were not observed in any of the patients. Our results suggest that TAI using fine-powder cisplatin can be safely administered for advanced HCC and can improve the prognosis of patients with advanced disease.

Angiogenesis plays an important role in tumor growth; therefore, inhibition of angiogenesis is considered a promising treatment strategy. Many signaling pathways, such as the vascular endothelial growth factor(VEGF)pathway, the Notch pathway, and the integrin pathway, are associated with each other in a complex manner; the VEGF signaling pathway plays a central role in angiogenesis. Bevacizumab is a humanized monoclonal antibody that specifically targets VEGF-A. Two large phase III trials, ECOG4599 and the AVAiL study, showed that bevacizumab combined with chemotherapy improves the outcome of patients with nonsquamous non-small cell lung cancer. Based on these results, bevacizumab is currently the only anti-angiogenic agent approved as the first-line of treatment for advanced nonsquamous non-small cell lung cancer in Japan. Many anti-angiogenic agents are currently in clinical development for the treatment of non-small cell lung cancer. These agents show antitumor activity by binding to a ligand and inhibiting the activation of receptor tyrosine kinases. However, bevacizumab is currently the only agent that extends overall survival. This review mainly discusses the results of a recent phase III trial with bevacizumab. We also discuss the results of a recent trial with new anti-angiogenic agents.

Capecitabine is one of the most effective oral chemotherapeutic drugs for advanced or recurrent colorectal cancer and gastric cancer. Capecitabine-containing chemotherapy is recommended as a first-line option for gastrointestinal tract cancer. The incidence of hand-foot syndrome (HFS), an adverse event of chemotherapy with capecitabine, is high. Moreover, once the symptoms of HFS are identified, they can significantly impair the quality of life (QOL) of patients. HFS should be managed by dose interruption and, if necessary, by dose reduction. Pharmacists and oncology nurses play an increasingly important role in the early identification and prevention of HFS through patient education and close clinical assessment. The aim of this study was to evaluate the efficacy of support tools for the early identification, prevention, and management of HFS and to assess the effectiveness of "patient self-check sheets". The patient was detected as having HFS of mild severity and had used a moisturizer at the time of initiation of therapy. Maintaining moisture retention is important in the management of HFS. The ambulatory team plays a key role by using self-check sheets to educate patients on how to recognize HFS, when to interrupt treatment, and how to adjust the dose so as to maintain effective therapy with capecitabine. For the continuation and completion of treatment and for maintaining an improved QOL in the home environment, supportive measures for adverse effects such as HFS and an ambulatory team are indispensable.

We report a case of the rechallenge of everolimus for metastatic renal cell carcinoma (RCC) after successful recovery from grade 3 interstitial lung disease (ILD). A 76-year-old man with metastatic RCC developed grade 3 ILD one month after the initiation of everolimus therapy (10 mg/day). ILD subsided in 4 months after the withdrawal of everolimus and treatment with corticosteroids. Half dose (5 mg/day) of everolimus was rechallenged for 9 months until another grade 3 ILD developed. Everolimus kept the disease under control for 13 months including the discontinuation period.

In Japan, prostate cancer is treated with non-steroidal anti-androgen (flutamide and bicalutamide). Development of breast pain during bicalutamide treatment, in prostate cancer patients reduces their quality of life (QOL) and treatment compliance. We studied the safety and effectiveness of switching from bicalutamide to flutamide in 13 prostate cancer patients who developed breast pain during bicalutamide treatment. We estimated the change in breast pain using a face scale and the Expanded Prostate Cancer Index Composite (EPIC) and EPIC-hormone domain (HD) score. The switch to flutamide relieved breast pain in nine patients, had no effect in one patient, and increased breast pain in two patients. One patient dropped out. Furthermore, summary score and hormone function were improved with a significant difference in the EPIC-HD score. Switching to flutamide in prostate cancer patients who develop breast pain during bicalutamide is safe and effective.