Here we report a case of successful treatment with combination chemotherapy of carboplatin(CBDCA)and paclitaxel for a patient undergoing hemodialysis(HD)with cancer of unknown primary, conducted by monitoring the observed AUC of ultrafilterable CBDCA. CBDCA was administered at a dose of 125 mg on day 1 in each course, an amount which had been calculated by the Calvert formula(GFR: 0, target AUC: 5). HD was started at a point in time one hour after the completion of each CBDCA administration, and performed for 5 hours in each course. Blood samples were collected during the first 3 courses of chemotherapy to measure the plasma concentration of free-platinum. The observed AUCs(o-AUC)of CBDCA in the first, second and third courses were 3. 03, 3. 44 and 3. 50mg·min/mL, respectively. The o-AUC in the first course was lower than that in the second course. The o-AUC in the second course was nearly equal to that in the third course, while each o-AUC was below the target AUC(t-AUC). Partial response was achieved after two courses of the CBDCA and paclitaxel combination chemotherapy, with adverse events of Grade 3 neutropenia and Grade 3 peripheral neuropathy observed in each course after the second course of chemotherapy. o-AUC of CBDCA administered to HD patients can not only be below t-AUC, as in this case, but also oppositely above t-AUC in cases with different doses of CBDCA or HD settings. Our results suggest that the monitoring of o-AUC of CBDCA is useful when practicing CBDCA-based chemotherapy safely and effectively in cancer patients undergoing HD.

Cancer patients have greater physical and mental anxiety than non-cancer patients because of the severity of their disease and the strong side effects of anticancer drugs. In this study, therefore, we sent out questionnaires to both cancer and noncancer patients to investigate the specific patient education for reducing anxiety of cancer patients, and compared the results in detail in Miyazaki Prefectural Miyazaki Hospital. The number of days of patient education was significantly more in cancer patients than in non-cancer patients. However, regardless of the number of days of patient education, understanding the level of side effects was significantly higher in cancer patients than in non-cancer patients. A significant correlation was shown between the relief level of patients and the listening level of pharmacists in both patient groups. Regarding the level of patient understanding, a significant correlation was shown between treatment methods and all of the other factors(effects of drugs, patients' degree of relief, pharmacists' degree of attentiveness). On the other hand, a significant correlation was shown only between treatment methods and effects of drugs on the level of understanding in non-cancer patients. These results suggest that characteristic patient education should be conducted for cancer patients, and that it would be best if it is done early on.

Molecularly targeted therapies have shown efficacy in many types of cancer, and the induction for their use is increasing rapidly. However, it is frequently associated with varied and unique cutaneous side effects, such as hand-foot-syndrome, rash, dry skin and paronychia. These effects, when severe or mild, tend to terminate the therapy because they inevitably impact the quality of life of patients. Treatment by emollients(steroids and moisturizing creams), topical antibiotics(MINO), topical corticosteroids, and antihistamines are accurately required at the early stages. Close interaction, among prescribers, dermatologists and nurses, is highly recommended in order to introduce preventative skin care(homeostasis)based on moisture retention, clean skin, and protection from agents. The side effects can be diagnosed and treated early by the multidisciplinary team. The balances between therapeutic benefit and cutaneous reaction should be considered, thus allowing for potentially greater success of anticancer therapy.

Platinum agents are widely used in cancer chemotherapy. Cisplatin, carboplatin, oxaliplatin and nedaplatin have a common chemical structure consisting of platinum, carrier groups and leaving groups, and undergo the similar mechanism of cytotoxicity. Only cisplatin induces nephrotoxicity, although the molecular mechanism involved is unclear. Organic cation transporter (OCT)/SLC22A, and multidrug and toxin extrusion (MATE)/SLC47A play a role in renal handling of cationic drug in the kidney. We focused on a role of transporters in nephrotoxicity of platinum agents. OCT2 mediates the transport of cisplatin and is the determinant of cisplatin-induced nephrotoxicity. In addition, MATE1 protects cisplatin-induced nephrotoxicity. Oxaliplatin, which was a superior substrate of the luminal efflux transporter, MATE2-K as well as OCT2, did not show nephrotoxicity. Moreover, carboplatin and nedaplatin were not transported by these transporters. Substrate specificity could regulate the features of platinum agents. Recent findings indicate that organic cation transporters are key to the nephrotoxicity of platinum agents.

Janus kinase 2 (JAK2) is an essential non-receptor type tyrosine kinase for various cytokine signals. In 2005, a somatic JAK2 mutation (V617F) was found in the majority of myeloproliferative neoplasm (MPN) patients. It has been shown that the V617F mutation caused the constitutive activation of JAK2, exhibiting the cytokine-independent survival and proliferation of Ba/F3 cells. In addition, tumorigenesis was induced after a transplantation of Ba/F3 cells expressing JAK2 V617F mutant in nude mice, suggesting that JAK2 V617F mutant behaves as a potent oncogene product. We found that JAK2 V617F mutant causes aberrant activation of a transcription factor c-Myc, which is critical for the JAK2 V617F mutant-caused oncogenic activities. In the screening of genes which expression was induced by JAK2 V617F mutant, we detected the significant induction of target genes of c-Myc such as Aurora kinase A (Aurka) and ornithine decarboxylase (ODC). Interestingly, JAK2 V617F mutant enhanced resistance to cisplatin (CDDP)-induced DNA damage and ectopic expression of Aurka in Ba/F3 cells exhibited similar resistance to CDDP. Conversely, knockdown and inhibition of Aurka in cells expressing JAK2 V617F mutant abolished the resistance to CDDP, suggesting that Aurka is most likely critical for resistance to DNA damage in cells transformed by JAK2 V617F mutant. In addition, we found that ODC inhibitor, DL-α-difluoromethylornithine (DFMO) prevented the proliferation of the JAK2 V617F mutant-induced transformed cells. Taking these observations together, c-Myc plays an essential role in JAK2 V617F mutant-induced hematopoietic disorder and would be a good target for the treatment of MPN.

A 64-year-old Japanese man who presented with a left renal mass (diameter, 9 cm) and multiple lung metastases, underwent translumbar left radical nephrectomy. Histological examination revealed the presence of clear cell-type, G3, pT3b renal cell carcinoma. Interferon-alpha (IFN-α) was administered postoperatively. Although the lung metastases were well controlled, radiological examination showed right renal metastasis and multiple brain metastases. γKnife was performed and chemotherapy was changed to sunitinib (50 mg/day). The patient developed a high fever on day 13 ; therefore, sunitinib administration was stopped on day 15. The next day, he presented with dyspnea, and chest computed tomography (CT) showed diffuse ground-glass opacities in both lungs. Bronchioalveolar lavage showed a predominance of lymphocytes, without any evidence of infection. We diagnosed the patient with interstitial lung disease (grade 3) attributable to sunitinib administration. After cessation of sunitinib therapy, chest CT showed that the shadows had resolved. We administered half of the previous dose of sunitinib 2 weeks after cessation of sunitinib therapy for complete resolution of the lung metastases. After the 2nd course of sunitinib, radiological examination showed tumor progression. Therefore, we replaced sunitinib with everolimus. Interstitial lung disease due to sunitinib therapy may be rare ; however, its occurrence should be considered when administering sunitinib.

Seven patients who had been receiving capecitabine+oxaliplatin±bevacizumab(CapeOX±BV)therapy at our hospital between February 2010 and March 2011, had complained of angialgia during oxaliplatin(L-OHP)administration. Therefore, 3. 3 mg of dexamethasone(DEX)was added to their infusion solution. The patients were then asked to rate their angialgia severity using a numerical rating scale(NRS), when L-OHP in a 5% dextrose solution was administered with or without DEX. By changing the L-OHP in 5% dextrose solution without DEX to the solution containing 3. 3 mg of DEX, the mean NRS was improved to 2. 4 from 7. 1. These findings indicate that L-OHP in 5% dextrose solution mixed with 3. 3 mg of DEX seems to be useful in reducing angialgia during peripheral administration of L-OHP.

Safety of pemetrexed mono-therapy in elderly patients with non-small-cell lung cancer was examined between May 2009 and April 2010 at Kobe City Medical Center General Hospital . The numbers of non-elderly and elderly(over 70 years old)patients were 14 and 19, respectively. Rates of neutropenia over Grade 3 were 14. 3% in the non-elderly group, and 36. 8% in the elderly group(p=0. 297). However, febrile neutropenia was only seen in one case in each group(p=0. 606), and no treatment-related death was observed. Although the rates of rash appearance were 28. 6% and 36. 8%(p=0. 347)for the non-elderly and the elderly, respectively, most rashes were relieved by steroids. From these results, pemetrexed mono-therapy is considered one of the applicable regimens for elderly patients.