Sorafenib(Nexavar)is a multikinase inhibitor, with disruptive activity at intracellular C-RAF, B-RAF and mutant BRAF receptors, and extracellular C-KIT, FLT-3, VEGFR-2, VEGFR-3 and PDGFRb receptors. In the phase III study, as compared with placebo, treatment with sorafenib significantly prolonged progression free survival(PFS)in patients with advanced renal cell carcinoma in whom previous therapy has failed. Diarrhea, rash, fatigue, hand-foot skin reactions, and hypertension were the most common adverse events associated with sorafenib. As sorafenib was associated with similar rates of clinically manageable side effects in elderly patients as compared to younger patients, response rates to sorafenib in elderly patients were comparable to those of younger patients. Sorafenib was approved multinationally for the treatment of advanced and/or metastatic renal cell carcinoma. Sorafenib and sunitinib are reference standards of care for the treatment of advanced renal cell carcinoma and are recommended by current clinical guidelines. For the future, research of biomarker, adverse drug reaction, and combined regimens are needed to maximize the effects of molecular-targeted drugs.

We report a patient who long had a complete response by chemotherapy with imatinib mesilate(IM)for locally recurrent gastrointestinal stromal tumor(GIST)of the stomach. On July 2000, a 58-year-old woman was pointed out to have anemia in the course of surveillance for malignant melanoma of skin. Endoscopic examination revealed continuous bleeding from a submucosal tumor with ulceration on the posterior wall of the stomach. After endoscopic homeostasis failed, emergency laparotomy was performed and a biopsy was also done. The diagnosis made was GIST from immunohistological findings of positive c-kit, positive CD34, negative HMB45, and negative S100. After diagnosis, total gastrectomy, distal pancreatectomy, and splenectomy were performed. On September 2003, a local recurrence was recognized, and then chemotherapy by 400 mg IM daily was started. After beginning with a dose of IM 400 mg daily, the reduction of the tumor was monitored. The IM dose then had to be reduced to 300 mg daily. Because of the adverse side effects of IM, systemic edema and body weight increased. After reduction of IM, the adverse reactions resolved promptly, and a complete response of the primary tumor has been maintained for 4 years 3 months.

In our department, S-1 has been administered for 1 year as postoperative adjuvant chemotherapy for advanced gastric cancer since 2000. It was started by a standard dosage of 4-week administration with 2 weeks rest since 2000(A group). However, since 2002, it was changed with the expectation of the reduction of side effects by 2-week administration with a one-week rest(B group). Treatment continuity, adverse events and efficacy in both A and B groups were examined.

Mitoxantrone was originally developed as an antineoplastic agent. However, it is currently used as an immunosuppressant in the treatment of multiple sclerosis (MS). A series of European studies over a 10-year period have revealed the clinical benefits and tolerability of mitoxantrone. On the basis of the favorable findings reported by the above mentioned studies, the FDA approved the use of mitoxantrone for reducing neurologic disability and/or the frequency of clinical relapses in patients with secondary progressive MS, progressive relapsing MS, or worsening relapsing-remitting MS but not for treating patients with primary progressive MS. The therapeutic modalities available in Japan are very limited. Interferon beta (IFN-beta), which is an immunomodulatory drug, is the only drug approved in Japan for treating MS; however, it is only partially effective or rather ineffective for treating patients with rapidly worsening or fulminant MS. Our pilot studies confirmed the benefits of mitoxantrone in Japanese patients with MS, and in this study, we review its potential appliciation for the treatment of MS by Japanese neurologists.

We examined 51 patients treated with Capecitabine for metastatic breast cancer. 51 patients achieved a 30.8% response rate, 59.6% a clinical benefit rate(59.6%)and 7.2 M of time to disease progression, as previously reported. Capecitabine therapy, single agent or combination therapy, should be considered a treatment of choice for metastatic breast cancer with certain response and general tolerability.

We report 2 cases of serum sickness after rituximab infusion. Case 1 is a patient with Waldenström's macroglobulinemia, and case 2 is a patient with marginal-zone B-cell lymphoma of mucosa-associated lymphoid tissue (MALT) type and Sjögren's syndrome. Both patients had polyclonal hypergammaglobulinemia, were treated with rituximab monotherapy, developed serum sickness between 9 and 17 days after the first rituximab infusion, developed fever and arthralgia, and improved soon after corticosteroid treatment. Serum sickness after rituximab treatment for hematological malignancies is very rare as far as we know. We identified three risk factors of serum sickness after rituximab infusion from previous reports and our cases; administration of rituximab alone, the existence of Sjögren's syndrome, and polyclonal hypergammaglobulinemia.

Recently, oxaliplatin(L-OHP)and irinotecan hydrochloride hydrate(CPT-11)have gained recognition as key drugs in the treatment of advanced colorectal cancer. In this article, we describe the results of a survey of medical institutions by pharmacists working at a pharmaceutical company. First, questions from medical institutions on L-OHP and CPT-11 were totaled and analyzed. The results showed that most of these questions concerned safety, with many of these addressing side effects. Next, a questionnaire on FOLFOX and FOLFIRI regimens was administered to medical institutions. The results indicated that staff are interested in the safety and critical path of these regimens. These results suggest that a lot of medical institutions require more information from pharmaceutical companies. This indicates that pharmacists should do more to take the needs of medical institutions into account in providing improved customer support.

Mirtazapine is a noradrenergic and specific serotonergic antidepressant(NaSSA). Some studies reported that mirtazapine has a receptor-binding profile that may be suitable for use in controlling appetite loss and nausea of cancer patients. We examined its efficacy for these symptoms in 9 cases administered mirtazapine for 9 days. After administration for 4-6 days, the efficacy of nausea was shown at 15 mg of the initial dosage; it was particularly useful in a mild stage. However, its efficacy for appetite loss was not clear for these cases. This study was performed by an open trial. Because of the small number of cases and follow-up period, future study is awaited.

The serine/threonine kinases, Akt and Pim, are key molecules for cell signaling downstream of growth factors, cytokines and other stimuli. Akt and Pim kinases regulate cellular processes that are associated with the aggressiveness of a number of different cancers. They protect cells from undergoing apoptosis and promote cell growth by phosphorylating their downstream substrates, which lead to the occurrence of resistance to anti-cancer drugs and radiation. Activation of Akt and Pim by transfecting their expression plasmids or by modulating their regulators attenuated the cytotoxic effects of anti-tumor drugs. Thus, the pathways are attractive targets for enhancing the sensitivity to and overcoming resistance to anti-cancer drugs. Recently, several small molecular inhibitors targeting the components of the Akt and Pim signaling pathways have been developed, and some inhibitors have already entered clinical trials. Further, some interesting associated proteins and substrates of the pathways have been identified. In future, new therapy targeting Akt and Pim signaling pathways will be developed to selectively induce apoptosis in cancer cells and to overcome drug resistance.

Among cases of therapy-related acute myeloid leukemia (t-AML) due to DNA topoisomerase II inhibitors, 11q23 abnormality is often detected. The usefulness of paclitaxel as a key drug in chemotherapy for breast cancer has been demonstrated. Few studies have reported t-AML due to paclitaxel. In this study, we report a patient who developed t-AML with 11q23 abnormality and bone marrow metastasis after breast cancer treatment with paclitaxel. The patient was a 61-year-old female who developed breast cancer at the age of 54 years. Four years after resection, lung and bone metastases were detected. Weekly therapy with paclitaxel at 80 mg/m2 was administered for 10 weeks (total dose: 1,200 mg), and radiotherapy was performed; thereafter, the extent of bone metastasis increased. Pancytopenia was noted 3 years after paclitaxel therapy. Bone marrow aspiration suggested AML (M4) with (11;19)(q23;p13) chromosome abnormalities. Histopathologically, bone marrow metastasis from breast cancer was detected in the same bone marrow specimen. This patient had not received any other anticancer drugs. Based on the clinical course, t-AML may have developed after paclitaxel therapy.

Stomatitis is a common side effect during cancer chemotherapy. We hypothesized that careful oral cavity care using patient guidance and cleanliness index prevents stomatitis in cancer chemotherapy. We introduced oral care patient guidance including teaching good brushing methods, O'Leary's Plaque Control Record(PCR)as a cleanliness index, and Eilers' Oral Assessment Guide(OAG)as an overall index after April 2006. We evaluated the incidence of stomatitis in 20 patients(10 patients between April 2004 to May 2006 and 10 patients after April 2006)with esophageal cancer who received chemotherapy including 5-FU and CDDP. Patients receiving brushing training after 2006 were evaluated regarding cleanliness of their oral cavities using PCR index and OAG index. The rates of stomatitis were 60%(6/10)and 40%(4/10)before and after the introduction of oral care patient guidance. The average of PCR index decreased from 82% to 46% after teaching good brushing method to the patients. The average of OAG index after brushing training was 9.14 which was better score compared with previous reports. Introduction of oral care patient guidance decreased the incidence of stomatitis. Both PCR and OAG indexes were useful in evaluating the objective condition of the oral cavity and in sharing patients' information among a medical team. These indexes encouraged the patients to clean their oral cavities.

Recently, drug delivery systems(DDS)have received increasing attention as a medical application of nanotechnology. Among them, polymeric micelles, self-assemblies of block copolymers, are a promising nanocarrier, because they can incorporate a variety of therapeutic agents such as hydrophobic substances, metal complexes and charged macromolecular compounds. Also, polymeric micelles have been demonstrated to effectively accumulate in the tumor tissue and show remarkable antitumor efficacy. Indeed, polymeric micelles encapsulating adriamycin, paclitaxel, cisplatin and SN-38 have progressed to clinical trials. This review deals with the development strategy and recent progress of polymeric micelles for the delivery of chemotherapeutic agents.

A 41-year-old man received allogeneic hematopoietic stem cell transplantation for T-cell lymphoblastic lymphoma. Recurrence occurred 20 months post-transplantation. Combination chemotherapy (etoposide, prednisolone, daunorubicin, vincristine) was performed, but the effect was limited, necessitating nelarabine administration. After 2 courses (1.5 g/m2/day, days 1, 3, 5), blood chemistry indicated severe liver injury. DDW-J 2004 guidelines on drug-induced liver injury indicated nelarabine as the most plausible etiologic agent. After administering ursodeoxycholic acid, phenobarbital and prednisolone, liver function improved. Although previous studies reported neurotoxicity as the most frequent and severe toxicity, we also need to consider that severe liver injury might be induced by nelarabine.

A paclitaxel injection NK (NK) is a generic product containing the same amount of ingredient as a Taxol Injection. We examined the pharmacokinetics and safety of NK compared to the original product in breast cancer patients. As a result, the transition of plasma paclitaxel concentration and pharmacokinetic parameter in NK and the original drug were almost equal, which suggested that these products were bioequivalent. In adjuvant therapy, there was no significant difference in adverse events reported, and these products were approximately equally safe.

The patient was a 73-year-old female with sigmoid colon cancer, who underwent resection of sigmoid colon cancer and liver metastasis. She was treated with 5-fluorouracil and levofolinate calcium(sLV5FU2)plus bevacizumab(BV) for advanced colorectal cancer. She was treated with angiotensin II receptor blocker(ARB)because hersystolic blood pressure was 200 mmHg and her diastolic blood pressure 100 mmHg after five courses of BV therapy. As a result, her blood pressure was controlled. It was possible to administer BV. Therefore, ARB may be the preferred antihypertensive agent in the management of BV-induced hypertension.