Nab-paclitaxel was administered to 9 patients with refractory advanced or recurrent breast cancer from 1 to 8 times(median 4)triweekly. The median cumulative dose was 775mg/m2(range 260-2, 000), and the median delivered dose intensity was 66. 7mg/m2/week(range 58. 3-86. 7). The response to treatment was CR in one patient, PR in 2 patients, SD in one patient, and PD in 4 patients. In one patient, treatment had to be suspended because of grade 3 peripheral neuropathy. The clinical benefit was 33%. All 4 PD patients were administered other salvage treatments and are alive. Adverse events included 6 case of neutropenia(grade 3-4 in 4 cases), grade 3 AST/ALT elevations in one patient, grade 3 myalgia in one patient. No case of febrile neutropenia was seen. All reactions were under control except for one patient with grade 3 peripheral neuropathy. Concurrent trastuzumab administration was safe also. In conclusion, nab-paclitaxel could be administered safely, and may contribute to the treatment of refractory advanced or recurrent breast cancer.

Some clinical studies confirmed the efficacy and safety of sorafenib in advanced hepatocellular carcinoma(HCC), for which the standard initial dose is 400 mg twice daily. However, it is unclear whether this dosage is tolerable for patients with a low body surface area(BSA). We retrospectively analyzed the difference in efficacy and safety of sorafenib between patients with low BSA and high BSA.

We report a 44-year-old man with acute lymphoblastic leukemia (ALL) presenting with fever and lymphadenopathy. Induction chemotherapy was initialed according to the JALSG ALL202 protocol, and L-asparaginase (L-asp) was given on days 20, 22, and 24 of therapy. Abrupt elevations of liver transaminase and bilirubin levels were observed on day 26. On day 30, coagulopathy and hepatic encephalopathy appeared. He was diagnosed with fulminant hepatitis and plasma exchange was performed, but he died on day 32, possibly due to L-asp-induced hepatitis. The common side effects of L-asp are hypersensitivity, ammonemia, coagulopathy, pancreatitis, convulsions, anaphylaxis, hepatotoxicity, and thrombosis. Although rare, reports of deaths due to hepatic failure during treatment with L-asp exist. L-asp is currently used for treatment of a wide range of hematological malignancies such as ALL and NK/T-cell lymphoma. A retrospective analysis of patients treated with L-asp should be carried out to elucidate the incidence and risk factors of liver dysfunction and fulminant hepatitis during L-asp treatment.

Reported here is the case of a 76-year-old male with gastric cancer. Distal gastrectomy was performed after his admission to our hospital. Histopathologically, the cancer was determined to be in the advanced stage. Combination chemotherapy with CDDP and S-1 was administered for 6 courses, after which S-1 was used alone. Chest X-ray and CT showed multiple dispersed lesions in the lung. Further examination by bronchoscope was performed. Histopathological examination of a biopsy specimen revealed the lesion to be organizing pneumonia. A drug-induced lymphocyte stimulation test (DLST) for S-1 proved to be positive. Discontinuation of S-1 administration led to natural improvement of the pneumonia. These results suggest that S-1 had induced the organizing pneumonia.

We examined the antiemetic effect and impact of aprepitant on the quality of life (QOL) of outpatients receiving moderately emetogenic chemotherapy (MEC). Data were compared between patients who received aprepitant (aprepitant group, n=30, treated May to September 2010) and those who did not (control group, n=14, treated February to April 2010). Controls received antiemetic treatment with a serotonin receptor antagonist and dexamethasone on Day 1. The aprepitant group received oral aprepitant (125 mg) concomitantly with these drugs on Day 1, and aprepitant (80 mg) on Days 2 and 3. The percentages of subjects without vomiting and nausea during the overall phase (0-96 h), acute phase (0-24 h), and delayed phase (24-96 h), and without loss of appetite during the entire period and delayed phase, were significantly higher in the aprepitant group. A QOL evaluation using the Functional Living Index-Emesis (FLIE) questionnaire showed a significantly higher percentage of subjects without the impact of nausea and vomiting disturbing their daily lives during the overall phase, and a significant decrease in QOL disturbance in the aprepitant group. Our results suggest that nausea, vomiting, loss of appetite, and QOL disturbance occur in many outpatients undergoing MEC, and that concomitant therapy with 3 drugs including aprepitant can improve symptoms and QOL of these patients.

Pemetrexed, a folate metabolic antagonist, is considered to be effective against plural mesotheliomas, non-small cell lung cancer, and especially for non-squamous cell cancer. However, it has been reported to have adverse interactions with nonsteroid anti-inflammatory drugs(NSAIDs). In the present study, we compared the incidence of adverse events between patients receiving pemetrexed therapy with and without concomitant NSAID administration. No significant difference in the incidence of hematotoxic events of Grade 3 or worse was observed. As for the incidence of non-hematotoxic events, the increase in the amount of creatinine, namely a severe adverse effect of Grade 2 or more, was significantly higher in the combined therapy group (p=0.018). No other significant differences were noted for other adverse events. A creatinine increase to Grade 2 or greater developed significantly earlier in the combined group(median value, 12.7 courses; p=0.0063). Our results suggest that renal dysfunction may easily develop as a result of continued pemetrexed administration combined with NSAID therapy. Therefore, it is necessary to take precautions against adverse side effects such as renal dysfunction when combining pemetrexed with NSAID therapy, by conducting periodic examinations.

A 79-year-old female had a spinal lesion that was definitely diagnosed as intravascular large B-cell lymphoma on the basis of skin biopsy findings, and she was treated by rituximab-containing chemotherapy. The spinal lesion showed high and low signal intensities on T₂ weighted magnetic resonance imaging (MRI) scans, those low signal intensity lesions were suspected to be hemorrhages. The hemorrhages were thought to have been caused by interaction between atypical lymphoma cells and the endothelial cells of spinal blood vessels, by hemorrhagic infarction or by rupture of the capillary endothelium due to interaction between rituximab and lymphoma cells. Intravascular large B-cell lymphoma cases rarely show low signal intensity on spinal T₂ weighted MRI scans.

The most effective drugs based on the type of cancer are chosen for chemotherapy. Tumor cells can be targeted at the DNA, RNA or protein level, and most of the classical anticancer drugs interact with tumor DNA in a time-dependent manner or a concentration-dependent manner. However, it has been unclear to date whether a combination therapy is carried out by using exact classification. Thus it is necessary to reclassify a great number of anticancer drugs. We propose a new classification system based on pharmacological effects of anticancer drugs. Classification of four anticancer drugs (cisplatin, carboplatin, paclitaxel and gemcitabine) was performed by the 3-(4,5-Dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay. The four anticancer drugs were grouped by IC50 values (inhibitory concentration, 50%) in a time-dependent manner and a concentration-dependent manner. The present approach may be combined to enhance the chemosensitivity, improve the dose of cytotoxic drugs and evaluate the effects of novel anticancer drugs.

This paper reports a specific and sensitive enzyme-linked immunosorbent assay (ELISA) for pharmacokinetic studies of vindesine (VDS). Anti-VDS antibody was obtained by immunizing rabbits with VDS conjugated with bovine serum albumin using N-[β-(4-diazophenyl) ethyl] maleimide as a heterobifunctional coupling agent. An enzyme marker was similarly prepared by coupling VDS with horseradish peroxidase using N-(4-diazophenyl) maleimide. The detection limit of VDS by ELISA was approximately 24 pg/mL with 50-mL samples. This assay was specific for VDS and showed very slight cross-reactivity with other vinca alkaloids, vincristine (0.18%) and vinblastine (0.11%). The values for the VDS concentrations detected using this assay were comparable with those detected using HPLC. There was a good correlation between the values determined by the two methods. Moreover, ELISA was about 50-fold more sensitive in detecting VDS at lower concentrations. The sensitivity and specificity of ELISA should provide a useful tool for pharmacokinetic studies of VDS.

We report two patients having hyperammonemic encephalopathy while being treated with chemotherapy for colorectal cancer. The first patient was a 69-year-old man with sigmoid colon cancer, having a massive invasion to the urinary bladder. He received SOX therapy following a pelvic exenteration operation. After the third course of SOX therapy, he presented with general fatigue and repeated seizures, and blood examination showed a high level of serum ammonium. He was diagnosed as hyperammonemic encephalopathy. The second patients was a 60-year-old woman with ascending colon cancer and liver metastasis having portal vein tumor thrombosis, who was given a palliative resection of ascending colon, and then underwent modified FOLFOX6 therapy. At the second course, she fell into a deep coma, and blood examination revealed a high level of serum ammonium. In both patients, treatment with infusion of branched-chain amino acid solutions resolved the symptoms of encephalopathy. Acute neurotoxicity caused by hyperammonemic encephalopathy during chemotherapy for colorectal cancer is rare and not well recognized, but it is a clinically important complication. We should pay more attention to hyperammonemic encephalopathy of patients receiving chemotherapy for colorectal cancer.

Gemcitabine hydrochloride is a very safe medicine that even outpatients can be administered, and the bone marrow depression that is the dose limiting factor remains moderate and does not need special treatment, although it is confirmed in most cases. Meanwhile, caution is required because there is a possibility of drug-induced lung injury and death due to high frequency, compared with the appearance rate described in the packaging insertion. We investigated the clinical background of a patient in whom drug-induced lung injury appeared, and clarified the risk factor by administering gemcitabine hydrochloride. Males, people aged 65 or over, those with a smoking history and those undergoing first-line chemotherapy treatment are at risk of drug-induced lung injury. Attention must be paid to the occurrence of drug-induced lung injury, to examining the clinical course, the chest image, and the blood test, and to do earlier detection, the offending medicine discontinuance, and beginning of the treatment.

There is a high frequency of serious side effects overseas in cases with a reduced creatinine clearance, for whom a 75% reduction in dose administration is recommended. The insidence of hematological toxicity was investigated in 89 cases[L group: Ccr<5 0mL/min(6 cases), M group: 50mL/min≤Ccr<80mL/min(34 cases), and H group: 80mL/min≤Ccr(49 cases)]who took capecitabine alone. The frequency of side effects was significantly high in group L[L: 6 cases(100%), M: 30 cases(88. 2%), and H: 30 cases(61. 2%)]. The frequency of grade 2 or more was higher in cases with a reduced renal function[L: 5 cases(83. 3%),M: 17 cases(50. 0%), and H: 18 cases(36. 7%)]. A significantly high decrease in hemoglobin was seen in group L[all grades; L: 5 cases(83. 3%),M: 20 cases(58. 8%), and H: 12 cases(24. 5%), and a grade 2 or more; L: 5 cases (83. 3%), M: 7 cases(20. 6%), and H: 5 cases (10. 2%)]. Moreover, there was little improvement when a decrease in hemoglobin occurred in grade 3 cases. Our findings suggest that it is necessary to manage drug dosage for Japanese patients while considering their renal function, and to actively monitor for any side effects.

Epirubicin hydrochloride(EPI)is well known to cause phlebitis as a typical adverse drug reaction. By preventing the development of severe phlebitis, patients are expected to continue effective chemotherapy with EPI without a decrease in QOL. We have previously reported promising results of a new injection method to prevent phlebitis from occurring during EPI therapy thorough a prospective clinical trial in our hospital(Jpn J Cancer Chemother 36: 969-974, 2009). In the present study, we have compared the conventional injection method(EPI main -route method, n=15)with our new method, which has been consistently practiced at present(EPI sub -route method, n=77). We found that in the EPI main -route method, angialgia/phlebitis developed in 14 of 15 cases(Grade 3, 53. 3%), leading to alteration of the regimen in 3 cases. On the other hand, with the EPI sub -route method, incidence of angialgia/phlebitis was markedly decreased, and only 6 of 77 cases developed these adverse reactions(Grade 3, 0%). One possible explanation for these results is that the reduction of intimal stimulation by the EPI sub -route method might be caused by the dilution and washout of EPI with pre-medication, as well as the shortened infusion times of EPI. Therefore, on the basis of the above hypothesis, we conclude that the EPI sub-route method might be a more effective treatment for the expected prevention of angialgia/phlebitis.

Aromatase inhibitors(AIs)are frequently employed for advanced or metastatic postmenopausal breast cancer as first-line hormone therapy. However, it is unknown which hormonal agent is the most appropriate after AI has failed.

To facilitate an optimal diagnosis and treatment of GIST in Japan, the Japanese Clinical Practice Guideline for GIST was proposed by the GIST Guideline Subcommittee. Multidisciplinary treatment planning is needed(involving pathologists, radiologists, surgeons and medical oncologists)for patients with GIST. Medical treatment is usually selected for unresectable GIST, metastatic GIST at the initial examination, and recurrent GIST. Imatinib is strongly recommended for patients with KIT-positive GIST; the standard dose of imatinib mesylate(Glivec)is 400 mg/day. For patients with imatinib-resistant GIST, Sunitinib (Sutent)is now approved in Japan and is covered by medical insurance. However, high-dose imatinib(>400mg/day)has not yet been approved in Japan.

Thymic epithelial neoplasm is a quite rare malignancy arising from the thymic epithelium, and comprises thymoma, thymic carcinoma, and thymic neuroendocrine carcinoma. The incidence of thymic carcinoma and neuroendocrine carcinoma is much less than thymoma, accounting for 1-4%of anterior mediastinal tumors. These rare tumors are called"orphan tumors,"and standards of clinical management(including chemotherapeutic regimens)have not yet been determined for them yet because of their rarity. In the advanced setting, palliative-intent chemotherapy has been applied using cisplatin-based triplet or quartet chemotherapy with second-generation antitumor drugs, with reference to chemotherapeutic regimens for invasive thymoma such as ADOC, CAP, and VIP chemotherapy. However, biological plausibility is lacking for this approach, given that these tumors differ from thymoma in their expression of cellular surface proteins such as c-Kit and epidermal growth factor receptors. While limited to thymic carcinoma, platinum doublet chemotherapy with a third-generation antitumor drug as first-line chemotherapy is anticipated to offer the same clinical efficacy as multiple-agent combination chemotherapy, but with less toxicities. In second-line or later-lines of chemotherapy, single-agent chemotherapy may be optimal. Molecular biological approaches have been under investigation, but molecular targeted agents remain unavailable.

A patient developed choroidal neovascularization (CNV) in one eye during treatment for bilateral recurrent central serous chorioretinopathy (CSC) and was intravitreously injected with bevacizumab; she developed multiple evanescent white dots and serous retinal detachment(SRD).