A Phase I Trial of 100mg/m2 Docetaxel in Patients with Advanced or Recurrent Breast Cancer

Docetaxel is a standard treatment for patients with advanced or recurrent breast cancer. The recommended dose is 60 to 100 mg/m2. Previous study have shown that the tumor response rates of patients who received docetaxel monotherapy at doses of 60, 75, and 100 mg/m2 were 22.1% , 23.3% , and 36.0% , respectively, and there was a significant relationship between the dose and response. In Europe and the United States, docetaxel is approved at a dose of 100 mg/m2, and Japanese guidelines also recommend a dose of 100 mg/m2. However, the approved dose in Japan is up to 75 mg/m2. We have launched a phase I trial evaluating 100 mg/m2 docetaxel in patients with advanced or relapsed breast cancer. The major eligibility criteria are as follows: age ≥20 years, pathologically diagnosed breast cancer, recurrent or advanced breast cancer, a good performance status, and HER2 [human epidermal growth factor receptor 2] negative. The primary endpoint is demonstrated safety of 100 mg/m2 docetaxel. This study will clarify whether 100mg/m2 docetaxel can be administrated safely in Japanese patients with advanced or recurrent breast cancer

Error Correction Activities Encourage Repeated Reading in Class

Repeated reading (RR) entails the reading of the same materials repeatedly and is a technique intended to develop reading fluency and comprehension for learners of English as a foreign language (EFL). However, the practice of RR today in classrooms throughout Japan is seemingly insufficient for several reasons. The present study focuses mainly on concentration and motivation for RR, which suggest that error correction activities (ECAs) are effective in encouraging RR. ECAs denote activities through which learners identify and correct several errors that are intentionally embedded in the text. This research examines whether ECAs enhance the concentration and motivation of learners for RR using a questionnaire. The results indicate that learners maintain concentration and motivation the most during ECAs, and that ECAs can be a catalyst for further RR

Monoclonal antibody pharmacogenomics in cancer treatment

Conventionally, in the pharmacokinetic/pharmacodynamic analysis of small molecule compounds such as cytotoxic anticancer drugs, polymorphism analysis of genes related to absorption, distribution, metabolism, and excretion has been performed in addition to the analyses of blood concentrations of drugs. Such pharmacogenetic factors play an important role in predicting therapeutic effects and adverse events and in the proper use of drugs. With the recent launch of immune checkpoint inhibitors (ICIs) and the rapid development of antibody-drug conjugates (ADCs) currently underway, there is no doubt that antibody drugs, which are large molecule compounds, will become key drugs in anticancer drug treatment. However, the pharmacokinetic and pharmacodynamic analysis of antibody drugs is still not sufficient, and further elucidation of factors and mechanisms affecting their dynamics in the human body is necessary. Moreover, the pharmacogenomic factors of antibody drugs have not yet been fully studied. There are many factors that should be clarified, such as factors that regulate the host immune response in ICI therapy and the effects of ATP-binding cassette transporter and cytochrome P450 on the payload of ADCs. This review provides an outline of antibody drugs in cancer treatment and summarizes the pharmacogenomic factors of antibody drugs known to date

One-Stage Laparoscopic Surgery for Pulmonary Sequestration and Hiatal Hernia in a 2-Year-Old Girl

We herein report a case of one-stage laparoscopic surgery for extralobar pulmonary sequestration (EPS) and hiatal hernia. Our patient was a 2-year-old girl who was diagnosed as a mediastinal mass lesion. Postnatal computed tomography revealed that the mediastinal mass was an EPS. Two weeks after birth, the patient developed gastroesophageal reflux (GER), and esophagography showed a hiatal hernia. At 2 years of age, she underwent one-stage laparoscopic Nissen's fundoplication for GER with resection of the EPS in the posterior mediastinum. The sequestrated lung was grasped via the esophageal hiatus; three aberrant blood vessels were dissected to allow removal of the sequestration through the umbilical port site. The esophageal hiatus was repaired and Nissen's fundoplication was performed laparoscopically. The patient's postoperative course was uneventful, with no recurrence of GER symptoms for 1 year. We conclude that one-stage laparoscopic surgery is useful for patients with EPS and hiatal hernia

Erlotinib-induced acute interstitial lung disease associated with extreme elevation of the plasma concentration in an elderly non-small-cell lung cancer patient

We herein describe a case of drug-induced interstitial lung disease (ILD) following treatment with erlotinib. The plasma trough concentration of erlotinib at the time of the ILD diagnosis was extremely elevated compared with the plasma maximum concentration on day 1. We hypothesized that this phenomenon was associated with the pharmacodynamic interaction with a concomitant drug. The present case indicates that erlotinib-induced ILD was associated with a high plasma concentration of erlotinib. Oncologists should be aware of the possibility of ILD induced by erlotinib, especially for patients with co-morbidities

ヤクブツ ドウタイ セイギョ インシ グン ノ イデンシ カイセキ ニ モトヅク コウガンヤク コベツ トウヨ セッケイホウ ノ キバン ケンキュウ

抗癌薬個別投与設計に有用と考えられる体内動態に影響を与える因子の探索を行った。アムルビシンに影響する薬物輸送タンパクとしてP 糖タンパク質であることを明らかにした。イマチニブの体内動態と投与量に影響を与える因子に体表面積が関与することを明らかにした。エルロチニブの皮膚毒性と体内動態にP 糖タンパク質の遺伝多型が影響することを明らかにした。本研究により、抗癌薬においても体内動態を制御する遺伝子群の解析が体内動態の個人間変動の解明に有効であることを示した

Biosafety studies of carrier cells infected with a replication-competent adenovirus introduced by IAI.3B promoter

The use of carrier cells infected with oncolytic viruses in cancer gene therapy is an attractive method because it can overcome viral immunogenicity and induce tumor immunity and significant antitumor activity. To enable human clinical trials of this treatment, acute and chronic toxicity tests must first be performed to ensure safety. IAI.3B promoter, oncolytic adenovirus AdE3-IAI.3B introduced by IAI.3B promoter, and A549 carrier cells infected with AdE3-IAI.3B were highly active in cancer cells but not in normal cells. Freeze-thawing increased the antitumor effect of A549 carrier cells by promoting the translocation of oncolytic adenovirus particles from the nucleus to the cytoplasm following the rupture of the nuclear membranes. No deaths or abnormal blood test data resulted from acute toxicity tests conducted in nude mice after a single dose. In chronic toxicity tests in rabbits, there were no serious side effects after eight doses of 1.25 × 107 cells/kg or less for 4 weeks; a significant immune response is known to elicit increased numbers of antiadenovirus antibodies and enlarge the spleen. From these results, it could be concluded that cancer gene therapy of recurrent solid tumors using carrier cells can be safely trialed in humans