Phase II study of first-line chemotherapy with uracil-tegafur plus oral leucovorin in elderly (≥75 years) Japanese patients with metastatic colorectal cancer: SGOSG-CR0501 study.

BACKGROUND: Oral uracil-tegafur and leucovorin (UFT/LV) therapy for elderly patients with metastatic colorectal cancer (mCRC) requires careful handling in Western countries because of a high incidence (≥20 %) of grade 3 diarrhea. However, its efficacy and safety for elderly Asian patients have not been investigated. METHODS: In this multicenter cooperative phase II study, the eligibility criteria were: age of 75 years or older, no prior chemotherapy, and histologically confirmed colorectal cancer with one or more measurable lesions. UFT 300 mg/m(2)/day and LV 75 mg/day were administered orally for 28 days followed by a 7-day rest period. RESULTS: Twenty-one patients were enrolled in this study (prior to study termination after approval of bevacizumab), and all patients were eligible for efficacy and safety analysis. The median age was 79 years (range, 75-83 years). The majority of patients (95 %) had ECOG Performance Status 0 or 1. The overall response rate was 33 % (95 % confidence interval [CI], 18-53 %). The median progression-free and overall survivals were 5.3 months (95 % CI 4.0-7.9 months) and 18 months (95 % CI 13-21 months), respectively. Grade 3 or greater adverse events included anorexia (10 %), diarrhea (10 %), and leukopenia (5 %). These results were compatible with those seen in Japanese patients in a previous bridging study between Japan and the US, in which patients under 75 years old were evaluated. CONCLUSIONS: UFT/LV therapy was safe and feasible in elderly Japanese patients with mCRC, and further study of UFT/LV therapy in combination with bevacizumab is warranted.

[A case of triple negative recurrent breast cancer successfully treated with capecitabine+docetaxel combination chemotherapy].

A 73-year-old woman underwent pectoralis-preserving mastectomy for left breast cancer (papillotubular carcinoma, f, T2, ly0, v0, N1 (21/21), T2N1M0 (Stage IIB), ER (-), PgR (-), HER2 (-)) in August 2004. It was called a triple negative breast cancer. She received systemic chemotherapy using AC followed by paclitaxel. In February 2006 (disease- free interval of one year and five months), skin and chest wall recurrences in the left breast were revealed. Systemic chemotherapy using capecitabine (1,800 mg/body/day) monotherapy resulted in PD after 4 courses. Subsequently, treatment with capecitabine+cyclophosphamide combination therapy resulted in PD after 6 courses. Since November 2006, treatment with capecitabine+docetaxel combination chemotherapy was initiated. Each course consisted of capecitabine at a dosage of 1,800 mg/body/day for 2 weeks and docetaxel at a dosage of 60 mg/body (day 8 only) followed by withdrawal for 1 week. After 3 courses, a marked response was seen, and a total of 6 courses were performed. No serious side effect was revealed, and a marked response has been maintained. It is suspected that capecitabine+docetaxel combination therapy is useful for a triple negative recurrent breast cancer which is refractory to systemic chemotherapy.

Using a Motion Sensor-Equipped Smartphone to Facilitate CT-Guided Puncture.

PURPOSE: To demonstrate the use of "Smart Puncture," a smartphone application to assist conventional CT-guided puncture without CT fluoroscopy, and to describe the advantages of this application. MATERIALS AND METHODS: A puncture guideline is displayed by entering the angle into the application. Regardless of the angle at which the device is being held, the motion sensor ensures that the guideline is displayed at the appropriate angle with respect to gravity. The angle of the smartphone's liquid crystal display (LCD) is also detected, preventing needle deflection from the CT slice image. Physicians can perform the puncture procedure by advancing the needle using the guideline while the smartphone is placed adjacent to the patient. In an experimental puncture test using a sponge as a target, the target was punctured at 30°, 50°, and 70° when the device was tilted to 0°, 15°, 30°, and 45°, respectively. The punctured target was then imaged with a CT scan, and the puncture error was measured. RESULTS: The mean puncture error in the plane parallel to the LCD was less than 2°, irrespective of device tilt. The mean puncture error in the sagittal plane was less than 3° with no device tilt. However, the mean puncture error tended to increase when the tilt was increased. CONCLUSION: This application can transform a smartphone into a valuable tool that is capable of objectively and accurately assisting CT-guided puncture procedures.

[Results of treatment of far advanced and recurrent stomach cancer with TS-1].

We used TS-1 as first-line therapy to treat 44 patients with far advanced or recurrent gastric cancer, and assessed the results and safety. One treatment cycle consisted of TS-1, 80 mg/m2/day, for 28 days followed by a 14-day rest period. The efficacy rate in the cases capable of being evaluated was 30.1% (11/36), and 25.0%, (7/28) when TS-1 was used as monotherapy. The efficacy rate was lower than in a phase II study, however, the median survival time (MST) of 10.7 months for the patients as a whole, the 1-year survival rate of 43.2%, and the 2-year survival rate of 20.5% were favorable. There were many NC cases in which long-term therapy was possible, and they contributed to the long-term survival. The incidence of adverse events was 84.1%, but the incidence of grade 3 or more events was low at 13.6%. Since TS-1 is highly efficacious and safe, as well as convenient because of being an oral preparation, it appears that it can be ranked as the drug of first choice for chemotherapy of far advanced or recurrent gastric cancer.

Randomized phase II study of gemcitabine and S-1 combination versus gemcitabine alone in the treatment of unresectable advanced pancreatic cancer (Japan Clinical Cancer Research Organization PC-01 study).

PURPOSE: To evaluate the efficacy and safety of the combination of gemcitabine (GEM) and S-1 (GS) in comparison to GEM alone (G) for unresectable pancreatic cancer. METHODS: In this multicenter randomized phase II study, we randomly assigned unresectable pancreatic cancer patients to either the GS group or the G group. The GS group regimen consists of intravenous 1,000 mg/m(2) GEM during 30 min on days 1 and 8, combined with 80 mg/m(2) oral S-1 twice daily on days 1-14, repeated every 3 weeks. On the other hand, the G group regimen consists of intravenous 1,000 mg/m(2) GEM on days 1, 8, and 15, repeated every 4 weeks. The primary endpoint was objective response rate (ORR). Secondary end points included treatment toxicity, clinical response benefit, progression-free survival (PFS), and overall survival. RESULTS: We registered 117 patients from 16 institutions between June 2007 and August, 2010. The ORR of the GS group was 28.3%, whereas that of the G group was 6.8%. This difference was statistically significant (P = 0.005). The disease control rate was 64.2% in the GS group and 44.1% in the G group. Median PFS was 6.15 months in the GS group and 3.78 month in the G group. This was also statistically significant (P = 0.0007). Moreover, the median overall survival (OS) of the GS group was significantly longer than that of the G group (13.7 months vs. 8.0 months; P = 0.035). The major grade 3-4 adverse events were neutropenia (54.7% in the GS group and 22.0% in the G group), thrombocytopenia (15.1% in the GS group and 5.1% in the G group), and skin rash (9.4% in the GS group). CONCLUSIONS: The GS group showed stronger anticancer activity than the G group, suggesting the need for a large randomized phase III study to confirm GS advantages in a specific subset.

The Arabidopsis RWP-RK protein RKD4 triggers gene expression and pattern formation in early embryogenesis.

Morphogenesis of seed plants commences with highly stereotypical cell division sequences in early embryogenesis [1, 2]. Although a small number of transcription factors and a mitogen-activated protein (MAP) kinase cascade have been implicated in this process [3-8], pattern formation in early embryogenesis remains poorly understood. We show here that the Arabidopsis RKD4, a member of the RWP-RK motif-containing putative transcription factors [9], is required for this process. Loss-of-function rkd4 mutants were defective in zygotic cell elongation, as well as subsequent cell division patterns. As expected from this mutant phenotype, RKD4 was transcribed preferentially in early embryos. RKD4 possessed functional characteristics of transcription factors and was able to ectopically induce early embryo-specific genes when overexpressed in seedlings. Strikingly, induced overexpression of RKD4 primed somatic cells for embryogenesis independently of external growth regulators. These results reveal that RKD4 is a novel key regulator of the earliest stage of plant development.