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Purpose: A phase III trial comparing S-1 and docetaxel with S-1 alone as postoperative chemotherapy for pathologically Stage III gastric cancer was conducted and clarified the superiority of the doublet in terms of 3-year relapse-free survival as the primary endpoint (67.7% versus 57.4%, hazard ratio [HR] 0.715, 95% confidence interval [CI] 0.587–0.871; p = 0.0008). This final report analyzed 5-year survival outcomes along with the incidence and pattern of late recurrences. Patients and methods: Patients with histologically confirmed Stage III gastric cancer who underwent gastrectomy with D2 lymphadenectomy were randomly assigned to receive adjuvant chemotherapy with either S-1 plus docetaxel or S-1 alone. The same 912 patients who were evaluated for 3-year survival outcomes in the previous report were analyzed. Results: Five-year overall survival rate of the S-1 plus docetaxel group (67.91%) was significantly superior to that in the S-1 group (60.27%; HR 0.752, 95% CI 0.613–0.922; p = 0.0059). The incidence of late recurrence at > 3 years after randomization was similar in both groups (7.3% versus 7.2%). Peritoneal dissemination was the most common pattern of late recurrence. Addition of docetaxel significantly suppressed relapse through the lymphatic (6.8% [95% CI 4.52–9.17] versus 15% [95% CI 11.76–18.30]; p < 0.0001) and hematogenous (10.2% [95% CI 7.37–12.94] versus 15.7% [95% CI 12.36–19.01]; p < 0.0137) pathways throughout the 5 years of follow-up. Conclusion: The survival benefit of postoperative chemotherapy with S-1 and docetaxel in terms of 5-year overall survival rate was confirmed for patients with pathologically Stage III gastric cancer, although late recurrences were not prevented. [ABSTRACT FROM AUTHOR]

Purpose: Metastatic breast cancer (MBC) is usually incurable; treatment aims to maximize patients' function and quality of life (QOL). Eribulin is a standard treatment in patients with MBC pretreated with anthracycline and taxane; however, the best administration schedule is unknown. Methods: In this prospective phase II trial of patients with luminal MBC, we administered biweekly eribulin to patients who completed a three-cycle induction treatment. Results: Sixty patients with hormone-receptor-positive and HER2-negative MBC were enrolled; 40 obtained stable disease (SD) or better efficacy after induction therapy, after which they were switched to biweekly maintenance administration. The median progression-free survival (PFS) in patients who switched to maintenance therapy was 15.21 weeks (95% CI 9.71–22.14), starting on the first day of maintenance therapy. Overall survival (OS) in patients who switched to maintenance therapy was 21.39 months (95% CI 18.89–32.89). PFS and OS in the whole population starting from the registration date were 19.00 weeks (95% CI 17.00–25.00) and 21.52 months (95% CI 16.23–24.25), respectively. PFS from the enrollment date for patients who received maintenance therapy was 25.29 weeks (95% CI 19.14–32.14). Patients who achieved complete response or partial response during induction therapy had significantly longer PFS compared to patients with SD. Conclusion: The efficacy of biweekly administration of eribulin at maintenance was nonsignificant. However, less frequent visits are convenient, and reduced dose intensity improves safety. Biweekly administration, besides dose reduction, could be an acceptable option for patients who are unable to maintain a standard regimen. [ABSTRACT FROM AUTHOR]

A correction notice has been issued for an article titled "Addition of docetaxel to S-1 results in significantly superior 5-year survival outcomes in Stage III gastric cancer: a final report of the JACCRO GC-07 study." The correction addresses an error in the Results section, specifically in the description of the number of events observed during the 5 years of follow-up. The correction clarifies that 426 events were observed, with 190 events in the S-1 plus docetaxel group and 236 events in the S-1 monotherapy group. The correction was made on May 22, 2024, and the authors apologize for the errors. [Extracted from the article]

Purpose: The second planned interim analysis (median follow-up 12.5 months) in a phase III trial of postoperative adjuvant chemotherapy for stage III gastric cancer revealed significant improvement in relapse-free survival (RFS) for S-1 plus docetaxel over S-1 alone. Although enrollment was terminated on the recommendation of the independent data and safety monitoring committee, we continued follow-up and herein report on 3-year RFS, the primary endpoint. Patients and methods: Patients with histologically confirmed stage III gastric cancer who underwent gastrectomy with D2 lymphadenectomy were randomly assigned to receive adjuvant chemotherapy with either S-1 plus docetaxel or S-1 alone. In the S-1 plus docetaxel group, S-1 was given orally for 2 weeks followed by 1 week of rest for seven courses, and docetaxel was given intravenously on day 1 of the second to seventh courses. The combination therapy was followed by S-1 monotherapy for up to 1 year. Results: The 3-year RFS rate of the S-1 plus docetaxel group was 67.7%. This was significantly superior to that of 57.4% in the S-1 group (hazard ratio [HR] 0.715, 95% CI 0.587–0.871, P = 0.0008). This translated into a significant benefit in the 3-year overall survival (OS) rate in the S-1 plus docetaxel group (77.7% versus 71.2%, HR 0.742, 95% CI 0.596–0.925, P = 0.0076). Conclusion: On 3-year follow-up data, postoperative adjuvant therapy with S-1 plus docetaxel was confirmed to improve both RFS and OS and can be recommended as a standard of care for patients with stage III gastric cancer treated by D2 dissection. [ABSTRACT FROM AUTHOR]

The efficacy of pharmacokinetically (PK) guided, once-daily administration of busulfan (BU) was evaluated in elderly patients with acute myeloid leukemia/myelodysplastic syndrome (AML/MDS). Twenty-one patients (median age 61) received 30 mg/m2 fludarabine for 6 days and BU for 4 days, starting from 3.2 mg/m2 and subsequently adjusted to the target area under the curve (AUC) of 6000 µmol-min/L. The median AUC of day 1 (AUC1), AUC4, and their average were 4871.3, 6021.0, and 5368.1 µmol-min/L, respectively. Veno-occlusive disease/sinusoidal obstructive syndrome (VOD/SOS) occurred in five patients (24%) but all recovered well. Four patients (20%) had non-infectious pulmonary complications (NIPCs). Patients with high AUC1 had frequent gastrointestinal adverse events, but similar incidence of VOD/SOS and NIPCs. Two-year overall survival (OS), non-relapse mortality (NRM), and relapse rates were 44.4%, 28.6%, and 29.1%, respectively. Patients with high AUC1 had significantly high NRM (57.1% vs. 14.3%, P = 0.04) and inferior OS (14.3% vs. 60.1%, P = 0.002), while patients with high AUC4 had a significantly low relapse rate (8.3% vs. 55.6%, P = 0.02). In conclusion, once-daily BU and a PK-guided dose intensification were beneficial for reducing relapse in elderly patients with AML/MDS. However, caution should be exercised as rapid BU dose elevation may contribute to NRM. [ABSTRACT FROM AUTHOR]

Introduction: Regorafenib is a multikinase inhibitor approved for the treatment of metastatic colorectal cancer (mCRC). Despite providing a statistically significant survival benefit, a substantial number of patients fail to respond to or continue with treatment, which has resulted in an unmet clinical need for a biomarker of regorafenib efficacy. Methods: The JACCRO CC-12 study was a prospective, multicenter, single-arm phase II trial designed to evaluate the usefulness of [18F]fluorodeoxyglucose positron emission tomography (FDG-PET) as an imaging biomarker of regorafenib in patients with mCRC that progressed after standard chemotherapies. FDG-PET and contrast-enhanced computed tomography (CT) were performed before and after treatment with regorafenib 160 mg once daily 3 weeks on/1 week off. The primary end point was the change in the maximum standardized uptake value in the lesion with the highest uptake at pre-treatment FDG-PET. The secondary end points included overall survival (OS), progression-free survival (PFS), the objective response rate (ORR), safety, and the correlation between FDG-PET and CT. Results: Twenty patients were enrolled from November 2014 to March 2016, 17 of whom were evaluated for metabolic and morphological changes. Metabolic response with FDG-PET was partial response (PR) in one case (5.9%), stable disease (SD) in four (23.5%), and progressive disease (PD) in 12 (70.6%). The metabolic response rate was 5.9%. On CT imaging, no complete response or PR was observed, and the ORR was 0%. Median PFS and OS were 1.7 and 9.8 months, respectively. The median PFS of patients who achieved PR or SD by FDG-PET was 3.7 months, whereas that of those assessed as PD was 1 month (p = 0.13). The median OS of patients who achieved PR or SD by FDG-PET was 13.0 months, whereas that of patients assessed as PD was 10.6 months (p = 0.43). Frequent adverse events were palmar–plantar erythrodysesthesia syndrome, hypertension, loss of appetite, and fatigue. Conclusions: In this study, FDG-PET failed to demonstrate usefulness as an early imaging biomarker of regorafenib in patients with mCRC. [ABSTRACT FROM AUTHOR]

Background: Regorafenib and trifluridine/tipiracil are standard third-line chemotherapies for colorectal cancer patients, but their efficacy is limited. Anti-epidermal growth factor receptor antibody rechallenge has been reported to be promising for patients who have obtained clinical benefit from first-line cetuximab-based chemotherapy. Moreover, panitumumab showed non-inferior efficacy to cetuximab. Objective: This study assessed the efficacy and safety of third-line panitumumab rechallenge in patients with metastatic KRAS exon 2 wild-type metastatic colorectal cancer who obtained clinical benefit from first-line panitumumab-based chemotherapy. Patients and Methods: This was a prospective, multicenter, phase II trial conducted from October 2013 to August 2017. Major eligibility criteria included KRAS exon 2 wild-type and achievement of complete response, partial response, or continued stable disease for at least 6 months in first-line panitumumab-based therapy. Irinotecan plus panitumumab treatment was continued until disease progression or unacceptable toxicity was observed. The primary endpoint was the 3-month progression-free survival (PFS) rate. Results: Twenty-five patients were enrolled in this study. Their median age was 66.5 years, and the 3-month PFS rate was 50.0% (95% confidence interval 30.0–70.0). The median PFS and overall survival were 3.1 months and 8.9 months, respectively. The response rate and disease control rate were 8.3% and 50.0%, respectively. Common grade 3/4 adverse events were acneiform rash (17%), hypomagnesemia (13%), and dry skin (13%). No treatment-related deaths occurred. Conclusion: Irinotecan plus panitumumab rechallenge is a promising third-line treatment regimen in patients with metastatic wild-type KRAS colorectal cancer. Clinical Trial Identification: UMIN000015916. [ABSTRACT FROM AUTHOR]

Background: Regorafenib or trifluridine/tipiracil as third-line treatment have limited efficacy in metastatic colorectal cancer (mCRC).Methods: This Phase 2 trial evaluated the efficacy and safety of irinotecan plus cetuximab rechallenge as third-line treatment in KRAS wild-type mCRC patients who achieved clinical benefit with first-line cetuximab-containing therapy. The primary endpoint was 3-month progression-free survival (PFS) rate. A sample size was calculated; 30 patients with a 3-month PFS rate of 45% deemed promising and 15% unacceptable. Patients with greater and less than the cut-off value of cetuximab-free intervals (CFIs) were classified into the long and short CFI groups, respectively, in subgroup analyses.Results: Among 34 eligible patients who received treatment at least once, 3-month PFS rate was 44.1% (95% confidence interval, 27.4-60.8%). The median PFS and overall survival (OS) were 2.4 and 8.2 months, respectively. The response and disease control rates were 2.9 and 55.9%, respectively. PFS and OS were significantly longer in the long- than in the short CFI group.Conclusions: Irinotecan plus cetuximab rechallenge as third-line treatment for KRAS wild-type mCRC was safe and had promising activity, especially in those with a long CFI, warranting further investigation in a Phase 3 randomised trial.Clinical Trial Registration: UMIN000010638. [ABSTRACT FROM AUTHOR]

Herein, we present a case of DHFL with central nervous system (CNS) involvement initially diagnosed as FL with breast involvement. Dear Editor: Follicular lymphoma (FL) is a common non-Hodgkin lymphoma with an indolent course but is incurable. [Extracted from the article]

Epstein–Barr virus (EBV)-positive mucocutaneous ulcer is a B-cell lymphoproliferative disorder occurring in elderly or iatrogenic immunocompromised patients. We report a 27-year-old male patient with Crohn's disease (CD) who developed immunomodulator-associated lymphoproliferative disorder. The patient was diagnosed with CD at the age of 17 and was treated with maintenance therapy including high-dose infliximab and azathioprine. When he was admitted to our hospital with a diagnosis of intestinal obstruction, his abdominal computed tomography findings showed not only colonic wall thickening and narrowing of the descending colon but also multiple liver tumor lesions. His ileus symptom improved with conservative therapy, and a pathological evaluation of the tissue biopsy specimens from the descending colon and liver lesions indicated a morphological diagnosis of EBV-positive diffuse large B-cell lymphoma. This was a case of iatrogenic immunodeficiency-associated lymphoproliferative disorder due to an immunomodulator. The treatment was initiated with chemotherapy, but he died of disease progression 10 months after the diagnosis of lymphoma. Although cases of lymphoproliferative disorder due to treatment modalities used for CD are rare in Japan, an increase in the risk of lymphoproliferative diseases should be considered in patients with CD treated with immunomodulatory agents. [ABSTRACT FROM AUTHOR]

Anti-platelet agents or anticoagulants are administered for patients with multiple myeloma (MM) receiving immunomodulatory drugs (IMiDs) to prevent thrombotic events (TEs). However, there is a discrepancy between current guidelines and clinical practice in thromboprophylaxis and the varied incidence of TEs depending on patient cohort. Therefore, a consensus on the optimal thromboprophylactic strategy is needed. To determine an appropriate strategy for the prevention of TEs in MM patients receiving IMiDs, we performed a retrospective single-institution analysis. In total, 95 MM patients (62% male, median age 65 years, range 30–85 years) from November 2008 to January 2018 were recruited, and 140 cases were analyzed in the medical-record-based study. Thromboprophylactic drugs were given to 69% of patients, anti-platelet agents to 66%, and anticoagulants to 3.0%. Seven TEs (5.0%) and six bleeding events (4.3%) were observed, but no patients died from thrombohemorrhage. The median follow-up period was 184 days (range 21–2224), and the cumulative TE incidence was 1.7% at 3 months, 7.0% at 1 year, and 12.5% at 3 years. Multivariate analysis determined that age > 70 years (p = 0.012) and BMI < 18.5 kg/m2 (p = 0.042) were the significant risk factors of TE. A low incidence of TEs was observed despite the low adherence to guideline recommendations for anticoagulant administration. These results suggest that anti-platelet agents are sufficient for thromboprophylaxis. A high-risk group of TEs in MM patients receiving IMiDs was identified, and a larger study is needed to confirm these findings. [ABSTRACT FROM AUTHOR]

Mediastinal gray zone lymphoma (MGZL) is a provisional entity with intermediate features between classical Hodgkin lymphoma (cHL) and diffuse large B-cell lymphoma. Outcomes for patients with MGZL are reportedly poorer than those for patients with cHL or primary mediastinal large B-cell lymphoma. Additionally, no standard management guidelines for patients with MGZL are available, primarily due to its recent identification, rarity, and challenges in diagnosis. Although recent several studies have suggested dose-adjusted EPOCH-R (etoposide, doxorubicin, vincristine, cyclophosphamide, prednisolone, and rituximab) may improve outcomes in patients with MGZL, numerous patients still suffer from relapsed/refractory MGZL, and the optimal management for such patients remains uncertain. Here, we report the first case of successful treatment of refractory MGZL by tandem high-dose chemotherapy supported by autologous stem cell transplantations (auto-SCTs) and consolidative radiotherapy (RT). To date, the patient remains in CR 33 months after the completion of RT, with no significant complications. This case suggests that tandem auto-SCTs may be a promising therapeutic option for relapsed/refractory MGZL. [ABSTRACT FROM AUTHOR]

Rationale: Quetiapine fumarate is an atypical antipsychotic indicated for various mental disorders, but it has not been studied in Japanese patients with bipolar depression.Objectives: To evaluate the efficacy and safety of quetiapine XR (extended release) in Japanese patients with bipolar depression.Methods: In this multi-center, randomized, double-blind, placebo-controlled, fixed-dose study of 431 Japanese adults with bipolar I or II disorder, efficacy was determined by analyzing the mean change from baseline in Montgomery-Åsberg Depression Rating Scale (MADRS) total score. Secondary end points included MADRS response and remission rates, Hamilton Depression Scale 17-Item (HAM-D17), and Clinical Global Impressions-Bipolar (CGI-BP) scale scores. Safety was determined by monitoring adverse events and clinical assessments.Results: This study revealed a statistically significantly greater decrease in MADRS total score after 8 weeks of quetiapine XR 300 mg/day monotherapy compared with placebo (− 12.6 vs. − 10.1; p = 0.034). There were also improvements in MADRS response (44.1 vs. 35.6%) and remission (38.0 vs. 26.6%) rates as well as in HAM-D17 and CGI-BP scale scores compared with placebo. In the subgroup analysis of patients with bipolar I or II disorder, the adjusted mean changes in MADRS total score compared to placebo were − 2.3 and − 2.1, respectively. Adverse events occurred in 149 patients (83.2%) receiving quetiapine XR 300 mg/day and in 81 patients (45.8%) receiving placebo. The most common adverse events were somnolence and thirst, which is consistent with the previously reported safety profile.Conclusions: Once-daily monotherapy with quetiapine XR is an effective and well-tolerated treatment for bipolar depression in Japanese patients. [ABSTRACT FROM AUTHOR]

Background: This open-label phase III trial evaluated efficacy and safety of S-1 plus cisplatin vs. cisplatin alone as first-line chemotherapy in patients with stage IVB, recurrent, or persistent cervical cancer.Methods: Patients were randomised (1:1) to S-1 plus cisplatin (study group) or cisplatin alone (control group). In each cycle, cisplatin 50 mg/m2 was administered on Day 1 in both groups. S-1 was administered orally at 80-120 mg daily on Days 1-14 of a 21-day cycle in the study group. The primary endpoint was overall survival (OS).Results: A total of 375 patients were enrolled, of whom 364 (188, study group; 176, control group) received treatment. Median OS was 21.9 and 19.5 months in the study and control groups, respectively (log-rank P = 0.125; hazard ratio [HR] 0.84, 95% confidence interval [CI] 0.67-1.05). Median progression-free survival (PFS) was 7.3 and 4.9 months in the study and control groups, respectively (HR 0.62, 95% CI 0.48-0.80, P < 0.001). The adverse event (AE) rate increased in the study group despite the absence of any unexpected AEs.Conclusions: S-1 plus cisplatin did not show superiority over cisplatin alone in OS but significantly increased PFS in patients with stage IVB, recurrent, or persistent cervical cancer. Since the standard therapy has changed in the course of this study, further studies are warranted to confirm the clinical positioning of S-1 combined with cisplatin for this population. [ABSTRACT FROM AUTHOR]

Background: FOLFOXIRI is now regarded as the chemotherapy regimen that offers the best platform for the treatment of colorectal cancer. However, the safety and efficacy of FOLFOXIRI + panitumumab has not been demonstrated. We conducted a phase I study to determine the recommended dose of FOLFOXIRI + panitumumab as first-line treatment for RAS wild-type metastatic colorectal cancer (mCRC).Methods: Patients received combination therapy consisting of panitumumab (6 mg/kg on day 1) + FOLFOXIRI [irinotecan (CPT-11), oxaliplatin (L-OHP) 85 mg/m2, and folinate (LV) 200 mg/m2] on day 1, followed by fluorouracil (5-FU) 3200 mg/m2 infused as a 46-h continuous infusion starting on day 1) repeated every 2 weeks as first-line treatment of RAS wild-type mCRC patients. A decrease in CPT-11 dose was planned (started at level 1: CPT-11 165 mg/m2).Results: Seven patients were enrolled, and six were assessed for safety and efficacy. Maximum tolerated dose was not reached at level 1; all patients were treated at these levels. The common Grade 3 or 4 relevant toxicities were diarrhea (50%), hypokalemia (33%) and stomatitis (33%). No treatment-related deaths occurred. Of the six patients assessed four had partial response and the two others had stable disease; hence, the response rate was 66.7% (95% confidence interval 28.9-100%) and the disease control rate was 100%. Time to protocol treatment failure was 7.2 (1.4-7.3) months.Conclusion: The FOLFOXIRI + panitumumab chemotherapy regimen was well tolerated by our patients with mCRC and showed promising anti-tumor activity. The recommended phase II dose was determined to be the same as the standard doses of this regimen used worldwide. [ABSTRACT FROM AUTHOR]

The aim of this study was to assess the safety and optimal dose of deferasirox for the treatment of iron overload after allogeneic hematopoietic cell transplantation (HCT). The primary endpoint was the maximum tolerated dose of deferasirox that was determined by the intrapatient dose escalation methods. A total of 16 patients with post-HCT iron overload were enrolled in the study. After excluding one case of early relapse, 15 remained evaluable. Their median age was 42 years (range 22-68). Median time from HCT to deferasirox administration was 9 months (range 6-84). Deferasirox was started at a dose of 5 mg/kg, and the dose was increased to 7.5 and 10 mg/kg every 4 weeks unless there were no grade ≥ 2 of adverse events. Achievement rates of planned medication were 80% in 5 mg/kg (12 of 15), 73% in 7.5 mg/kg (11 of 15), and 60% in 10 mg/kg (9 of 15), respectively. The reasons for discontinuation of the drug were grade 2 of adverse events (n = 4), late relapse (n = 1), and self-cessation (n = 1). None of the patients developed grade ≥ 3 of adverse events or exacerbation of GVHD. Among 11 evaluable cases, mean value of ferritin decreased from 1560 ng/ml pre-treatment to 1285 ng/ml post-treatment. These data suggested that 10 mg/kg of deferasirox may be maximum tolerated dose when given after HCT. Our dose escalating method of deferasirox is useful to identify the optimal dosage of the drug in each patient.Trial Registration: UMIN000011251. [ABSTRACT FROM AUTHOR]

Background: S-1 plus cisplatin is a standard regimen for advanced gastric cancer (AGC) in Asia. The ToGA trial established a fluoropyrimidine plus cisplatin and trastuzumab as a standard treatment for human epidermal growth factor receptor 2 (HER2)-positive AGC. In the HERBIS-1 trial, trastuzumab combined with S-1 plus cisplatin showed promising antitumor activity in patients with HER2-positive AGC. However, cisplatin has several important drawbacks, including vomiting and renal toxicity. These disadvantages of cisplatin are prominent in elderly patients. Therefore, we conducted a prospective phase II study of trastuzumab plus S-1 without cisplatin in elderly patients with HER2-positive AGC.Methods: Patients 65 years or older who had HER2-positive AGC received S-1 orally on days 1-28 of a 42-day cycle and trastuzumab intravenously on day 1 of a 21-day cycle.Results: A total of 51 patients were enrolled. Two patients were ineligible. The full analysis set thus comprised 49 patients. The median age was 71 years (range 65-85). The confirmed response rate was 40.8% (95% CI 27.1-54.6%), and the null hypothesis was rejected. The median follow-up period was 10.6 months. Median overall survival was 15.8 months. Median progression-free survival was 5.1 months, and time to treatment failure was 4.0 months. Major grade 3 or 4 adverse events included neutropenia (12.0%), anemia (24.0%), diarrhea (10.0%), and anorexia (12.0%). There was one treatment-related death.Conclusions: Trastuzumab in combination with S-1 alone demonstrated promising antitumor activity and manageable toxic effects as well as promising survival results in elderly patients with HER2-positive AGC.Clinical trials registration: UMIN000007368. [ABSTRACT FROM AUTHOR]

Thrombopoietin-receptor agonists have been recently introduced for a second-line treatment of immune thrombocytopenia (ITP). Splenectomy has tended to be avoided because of its complications, but the response rate of splenectomy is 60-80% and it has still been considered for steroid-refractory ITP. We performed partial splenic embolization (PSE) as an alternative to splenectomy. Between 1988 and 2013, 91 patients with steroid-resistant ITP underwent PSE at our hospital, and we retrospectively analyzed the efficacy and long-term outcomes of PSE. The complete response rate (CR, platelets > 100 × 109/L) was 51% (n = 46), and the overall response rate (CR plus response (R), > 30 × 109/L) was 84% (n = 76). One year after PSE, 70% of patients remained CR and R. The group with peak platelet count after PSE ≥ 300 × 109/L (n = 29) exhibited a significantly higher platelet count than the group with platelet count < 300 × 109/L (n = 40) at any time point after PSE. The failure-free survival (FFS) rates at 1, 5, and 10 years were 78, 56, and 52%, respectively. Second PSE was performed in 20 patients who relapsed (n = 14) or had no response to the initial PSE (n = 6), and the overall response was achieved in 63% patients. There were no PSE-related deaths. These results indicate that PSE is a safe and effective alternative therapy to splenectomy for patients with steroid-resistant ITP as it generates long-term, durable responses. [ABSTRACT FROM AUTHOR]

Ruxolitinib, a potent JAK1/JAK2 inhibitor, was found to be superior to the best available therapy (BAT) in controlling hematocrit, reducing splenomegaly, and improving symptoms in the phase 3 RESPONSE study of patients with polycythemia vera with splenomegaly who experienced an inadequate response to or adverse effects from hydroxyurea. We report findings from a subgroup analysis of Japanese patients in RESPONSE (n = 18). The composite response rate (hematocrit control and spleen response) was higher in patients receiving ruxolitinib (50.0%) than in those receiving BAT (8.3%). A total of 50.0% of patients randomized to ruxolitinib achieved a spleen response vs 8.3% of those receiving BAT; 100 and 33.3% of patients in the respective groups achieved hematocrit control, with mean hematocrit in ruxolitinib-treated patients remaining stable at < 45% throughout the study. Similarly, a higher proportion of ruxolitinib-treated patients achieved complete hematologic remission (33.3 vs 16.7%). Ruxolitinib also led to rapid improvements in pruritus. All responses with ruxolitinib were durable to week 80, and its safety profile was consistent with that in the overall study. These findings suggest that ruxolitinib is an effective and well-tolerated treatment option for Japanese patients with polycythemia vera with an inadequate response to or adverse effects from hydroxyurea. [ABSTRACT FROM AUTHOR]

Background: The decrease in carcinoembryonic antigen (CEA) level is faster and greater during cetuximab treatment than bevacizumab treatment and correlates with prolonged survival in patients with metastatic colorectal cancer (mCRC) who receive cetuximab.Objective: We investigated if the degree of change in the CEA value can serve as a diagnostic tool for predicting survival, as well as tumor regression in mCRC patients treated with cetuximab combined regimen as first-line treatment.Patients and Methods: Associations among the CEA decrease, depth of response (DpR), and clinical outcomes were evaluated in 113 patients with mCRC from two phase II trials of first-line therapy: the JACCRO CC-05 trial of cetuximab plus FOLFOX and the CC-06 trial of cetuximab plus SOX. Analysis was performed using Spearman's rank correlation coefficient. A 75% decrease in the CEA was used as the cut-off value to define the CEA response and discriminate CEA responders on the basis of the results of a previous study.Results: Ninety-two patients were eligible for analyses of both CEA and DpR. The median CEA decrease was 67.4%, and the median time to CEA nadir was 2.8 months, which was similar to the median time to DpR of 3.0 months. The DpR was associated with PFS and OS (rs = 0.56, P < 0.0001; rs = 0.39, P = 0.0090, respectively); moreover, the CEA decrease correlated with PFS (rs = 0.56, P < 0.0001), as well as OS (rs = 0.35, P = 0.019). CEA responders had significantly longer PFS (11.8 vs. 5.5 months, hazard ratio [HR] 0.46, P = 0.0009) and slightly, but not significantly longer OS (36.2 vs. 23.5 months; HR 0.57; P = 0.072) than CEA non-responders. The CEA decrease was statistically significantly associated with the DpR (rs = 0.44, P < 0.0001).Conclusions: Our study demonstrates that both DpR and CEA response correlate with clinical outcomes of first-line treatment with cetuximab. The CEA decrease may serve as a surrogate for DpR in patients who receive first-line cetuximab treatment (UMIN000004197, UMIN000007022). [ABSTRACT FROM AUTHOR]

Background: Retrospective studies have found that early tumor shrinkage (ETS) and depth of response (DpR) are associated with favorable outcomes in patients with metastatic colorectal cancer (mCRC); however, few prospective studies have evaluated ETS and DpR.Patients and Methods: We performed a phase II study of FOLFOX plus cetuximab as first-line treatment in Japanese patients with KRAS wild-type mCRC. The primary endpoint was response rate (RR), and secondary endpoints included progression-free survival (PFS), overall survival (OS), chronological tumor shrinkage (evaluated every 8 weeks), and safety. The association of ETS and DpR with survival time was analyzed using Spearman's rank correlation coefficient.Results: In 54 participants, the RR, median PFS, and OS were 66.7 % (95 % CI, 53.4-77.8 %), 11.1 months, and 33.9 months, respectively. There was no unexpected toxicity. Forty (80 %) of 50 assessable patients had ETS, which was associated with prolonged PFS and OS (11.3 vs. 3.7 months, HR 0.26, p = 0.0003; 42.8 vs. 9.0 months, HR 0.40, p = 0.0279, respectively). Median DpR was 56.3 %. The DpR correlated with OS (r s = 0.314, p = 0.027) as well as post-progression survival (PPS) (r s = 0.366, p = 0.017). Interestingly, DpR was moderately associated with OS and PPS (r s = 0.587, r s = 0.570, respectively) in patients harboring tumors with larger target lesions, but was not associated with OS or PPS in patients with smaller target lesions. FOLFOX plus cetuximab was active as a first-line treatment for Japanese mCRC patients, with no unexpected toxicities.Conclusions: Our prospective evaluation of chronological tumor shrinkage showed that ETS and DpR correlate with outcomes in patients with KRAS wild-type mCRC who receive cetuximab-based chemotherapy (UMIN000004197). [ABSTRACT FROM AUTHOR]

The article presents a case study of 84-year-old immunocompetent woman with signoid resection for acute colonic diverticulitis. It notes the identification of clonal immunoglobulin gene (Ig) rearrangement, T cell receptor (TCR) rearrangement, Epstein-Barr virus (EBV)-positive mucocutaneous ulcer (EBVMCU) in colon diverticulitis.

Purpose: In the CATS (Cisplatin And TS-1) randomized trial comparing cisplatin plus either docetaxel (DP arm) or TS-1 (SP arm) in lung cancer, efficacy was found to be equivalent but the global quality of life (QOL) score was higher in the SP arm. The purpose of the current study was to identify which of the adverse events (AEs) contributed to the deterioration of QOL. Methods: QOL and AE data from the CATS trial were used to quantitatively analyze the relationship between deterioration of QOL score and occurrence of AEs. Subtracted values of the QOL score from post-chemotherapy to pre-chemotherapy were fully compared between patients with or without each AE (Student's t test, significance level = 0.001). Multivariate linear regression analysis was also performed. Analysis of variance was performed to identify whether grade of AE(s) might be significantly correlated with the deterioration of the QOL score (significance level of 0.05). Results: As expected, gastrointestinal (GI) toxicities were associated with worsening of a variety of QOL items in both trial arms, detected by both univariate and multivariate analysis ( p < 0.001 and p < 0.0001, respectively). Multivariate analysis unpredictably indicated that an increase in serum bilirubin level was the only AE that was uniquely associated with worsening of physical functioning ( p = 0.0002), cognitive functioning ( p < 0.0001), and financial problems ( p = 0.0005) in the DP arm, although not in the SP arm. GI toxicities tended to be prolonged in the SP arm. Conclusion: An increase in serum bilirubin level may contribute to the worse global QOL of subjects in the DP arm in the CATS trial. The method we used here may be a unique approach to identify unpredictable AE(s) that worsen the QOL of patients treated by chemotherapy. [ABSTRACT FROM AUTHOR]

Background: Although postoperative adjuvant chemotherapy with S-1, an oral fluoropyrimidine, has become a standard of care for gastric cancer in Japan, nonresponders may suffer from the cost and adverse reactions without clinical benefit. This multicenter exploratory phase II trial was conducted to see whether a chemosensitivity test, the collagen gel droplet embedded culture drug sensitivity test (CD-DST), can adequately select patients for chemotherapy. Methods: The CD-DST using four different concentrations of 5-fluorouracil was conducted with resected specimens from preregistered patients who underwent gastrectomy with D2 or more extensive lymphadenectomy. Patients who were histopathologically confirmed to have stage II or greater disease without distant metastasis were eligible for final enrollment. All patients underwent protocol-specified adjuvant chemotherapy with S-1. Three-year relapse-free survival was compared between patients determined as sensitive by the CD-DST (responders) and those deemed insensitive (nonresponders). Appropriate cutoff values for in vitro growth inhibition were defined when the hazard ratio for relapse in responders and the log-rank P values were at their minimum. Results: Of the 311 patients enrolled, 14 were ineligible and 27 failed to start the protocol treatment. The CD-DST failed in 64 other patients, and survival analyses were conducted with the remaining 206 patients (39 stage II disease, 155 stage III disease, and 12 stage IV disease). The outcome of patients who were determined to be responders was significantly superior to that of nonresponders regardless of the 5-fluorouracil concentrations, although no differences in clinicopathologic characteristics were observed between the two groups, except for age. Conclusions: The CD-DST identified those who benefit from adjuvant chemotherapy. It deserves further evaluation in the setting of a prospective randomized trial. ClinicalTrials.gov identifier: NCT00287755 [ABSTRACT FROM AUTHOR]

Purpose: To define the effects of body mass index (BMI) on operative outcomes for both gastroenterological and cardiovascular surgery, using the National Clinical Database (NCD) of the Japanese nationwide web-based database. Methods: The subjects of this study were 288,418 patients who underwent typical surgical procedures between January 2011 and December 2012. There were eight gastroenterological procedures, including esophagectomy, distal gastrectomy, total gastrectomy, right hemicolectomy, low anterior resection, hepatectomy of >1 segment excluding the lateral segment, pancreaticoduodenectomy, and surgery for acute diffuse peritonitis ( n = 232,199); and five cardiovascular procedures, including aortic valve replacement, total arch replacement (TAR), descending thoracic aorta replacement (descending TAR), and on- or off-pump coronary artery bypass grafting ( n = 56,219). The relationships of BMI with operation time and operative mortality for each procedure were investigated, using the NCD. Results: Operation times were longer for patients with a higher BMI. When a BMI cut-off of 30 was used, the operation time for obese patients was significantly longer than that for non-obese patients, for all procedures except esophagectomy ( P < 0.01). The mortality rate based on BMI revealed a U-shaped distribution, with both underweight and obese patients having high mortality rates for almost all procedures. Conclusions: This Japanese nationwide study provides solid evidence to reinforce that both obesity and excessively low weight are factors that impact operative outcomes significantly. [ABSTRACT FROM AUTHOR]

Purpose: Biochemical modulation of 5-fluorouracil (5-FU) by leucovorin (LV) enhances antitumor activity. LV is thus often added to 5-FU-based regimens for the treatment of metastatic colorectal cancer (mCRC). A combination of S-1, oxaliplatin, and LV (SOL) was shown to be feasible, effective, and safe in a previous phase I trial. We therefore conducted a randomized phase II trial to evaluate efficacy and safety of SOL compared with mFOLFOX6. Methods: Patients with mCRC and no prior chemotherapy were randomly assigned to receive either SOL or mFOLFOX6. SOL consisted of S-1 (40-60 mg bid) plus oral LV (25 mg bid) for 1 week and oxaliplatin (85 mg/m) on day 1, repeated every 2 weeks. Results: Among 107 patients enrolled from July 2008 through July 2009, 105 (56 in the SOL group and 49 in the mFOLFOX6 group) were eligible and evaluated. The median progression-free survival was 9.6 months in the SOL group and 6.9 months in the mFOLFOX6 group [hazard ratio (HR) 0.83, 95 % confidence interval (CI) 0.49-1.40]. The median overall survival was 29.9 and 25.9 months, respectively (HR 0.91, 95 % CI 0.55-1.49). The response rate was 55 % in both groups. Grade 3 or 4 adverse drug reactions were neutropenia (20 % with SOL vs 41 % with mFOLFOX6), sensory neuropathy (20 vs 2.0 %), anorexia (13 vs 7.8 %), fatigue (11 vs 5.9 %), and diarrhea (11 vs 3.9 %). Conclusions: SOL demonstrated promising efficacy and acceptable toxicity as first-line chemotherapy for mCRC. Further studies of SOL combined with molecular target agents are warranted. [ABSTRACT FROM AUTHOR]

Rotigotine, a non-ergot dopamine receptor agonist, offers potential for continuous dopaminergic stimulation that could avoid the fluctuations observed with traditional treatments. We conducted a randomized, double-blind, placebo-controlled trial in Japanese patients with advanced Parkinson's disease (PD) to investigate the efficacy and safety of rotigotine. Inclusion criteria included the presence of motor complications, such as wearing off, on-off, delayed-on/no-on, any circumstances that could interfere with levodopa dose escalation because of side effects, or declining levodopa efficacy. The enrolled patients received once-daily applications of rotigotine transdermal patches or matched placebo patches. A total of 174 patients were randomly assigned to rotigotine (87 patients) or placebo (87 patients). The full analysis set included 172 patients (86 for the rotigotine group and 86 for the placebo group). The maximum maintenance dose of rotigotine was set at 16 mg/24 h. The changes in unified PD rating scale Part III scores from baseline to the end of the trial were −10.1 ± 9.0 (mean ± standard deviation) in the rotigotine group and −4.4 ± 7.4 in the placebo group ( p < 0.001). There was a significantly greater reduction in the off-time ( p = 0.014) in the rotigotine group. Rotigotine was well tolerated, with serious adverse events being reported in only three patients in each group. Rotigotine at doses of up to 16 mg/24 h is efficacious and safe in Japanese patients with advanced PD. [ABSTRACT FROM AUTHOR]

Philadelphia chromosome-positive mixed phenotype acute leukemia (Ph(+)MPAL) is a rare type of acute leukemia having myeloid and lymphoid features. In the present study, we describe the successful treatment of a 71-year-old Japanese female patient with Ph(+)MPAL by the alternation of second-generation tyrosine kinase inhibitors according to BCR-ABL1 mutations. The patient survived in her third complete remission (CR) for over 4 years. In her first CR, the patient was treated with multiple-agent chemotherapy and underwent maintenance therapy with imatinib and monthly vincristine and prednisolone (VP). At the first relapse, an examination of the bone marrow revealed a transformation into acute lymphoblastic leukemia and an F317L mutation in BCR-ABL1 gene, which responded preferentially to nilotinib over dasatinib. She achieved second CR, and nilotinib with VP therapy was selected for maintenance treatment. At second relapse, BCR-ABL1 mutational analysis revealed Y253H mutation instead of F317L mutation, resulting in resistance to nilotinib. The patient achieved third CR with dasatinib and VP therapy, and maintained CR with this treatment. This suggests that appropriate alternation of TKIs may contribute to long-term survival in elderly patients with Ph(+)MPAL. [ABSTRACT FROM AUTHOR]

Purpose: Cisplatin plus 5-fluorouracil has been globally accepted as a standard regimen for the treatment for advanced gastric cancer. However, cisplatin has several disadvantages, including renal toxicity and the need for admission. S-1 plus cisplatin has become a standard treatment for advanced gastric cancer in East Asia. This phase III study was designed to evaluate the potential benefits of adding docetaxel to S-1 without a platinum compound in patients with advanced gastric cancer. Methods: Patients were randomly assigned to receive docetaxel plus S-1 or S-1 alone. The docetaxel plus S-1 group received docetaxel on day 1 and oral S-1 on days 1-14 of a 21-day cycle. The S-1 alone group received oral S-1 on days 1-28 of a 42-day cycle. The primary end point was overall survival. Results: Of the 639 patients enrolled, 635 were eligible for analysis. The median overall survival was 12.5 months in the docetaxel plus S-1 group and 10.8 months in the S-1 alone group ( p = 0.032). The median progression-free survival was 5.3 months in the docetaxel plus S-1 group and 4.2 months in the S-1 alone group ( p = 0.001). As for adverse events, neutropenia was more frequent in the docetaxel plus S-1 group, but remained manageable. Conclusion: As first-line treatment for advanced gastric cancer, docetaxel plus S-1 significantly improves median overall and progression-free survival as compared with S-1 alone. (ClinicalTrials.gov number: NCT00287768). [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this multicenter phase II study was to evaluate the efficacy and safety of a combination of irinotecan, 5-fluorouracil (5-FU), and leucovorin (FOLFIRI) plus bevacizumab as first-line chemotherapy in Japanese patients with metastatic colorectal cancer. Methods: Patients with metastatic colorectal cancer were eligible for enrollment. On day 1 of a 14-day cycle, patients received bevacizumab 5 mg/kg, irinotecan 150 mg/m, and l-leucovorin 200 mg/m as an intravenous infusion, followed by 5-FU 400 mg/m as an intravenous bolus and then 5-FU 2,400 mg/m as an 46-h intravenous infusion. This treatment cycle was repeated. The primary endpoint was progression-free survival (PFS). Results: We enrolled 40 patients, but one withdrew consent before starting treatment. The remaining 39 patients received a total of 509 cycles of FOLFIRI plus bevacizumab (median 11 per patient; range 1-30). The median PFS was 11.5 months, the median overall survival (OS) was 22.0 months, and the 1-year OS rate was 81.8 %. All 39 patients had adverse events. Grade 3 or 4 neutropenia and stomatitis occurred in 21 (53.9 %) and 4 (10.3 %) patients, respectively. Conclusion: Our results suggest that FOLFIRI plus bevacizumab is a clinically effective regimen with a manageable toxicity profile as first-line chemotherapy in patients with metastatic colorectal cancer. [ABSTRACT FROM AUTHOR]

Although previous studies have reported that onset at young age is associated with poor prognosis in breast cancer, the correlation between reproductive factors, breast cancer characteristics, and prognosis remains unclear. Five hundred and twenty-six premenopausal young women diagnosed with primary invasive breast cancer between January 2000 and December 2007 were included in this study. Patients were classified into four groups according to their reproductive history: women who gave birth within the previous 2 years (group A), women who gave birth between 3 and 5 years previously (group B), women who gave birth more than 5 years previously (group C), and nulliparous women (group N). The correlation between the time since last childbirth to diagnosis, histopathological tumor features, and breast cancer prognosis was evaluated. Breast cancer patients who had given birth more recently had more advanced stage tumors; larger sized tumors; a higher rate of axillary lymph node metastases; a higher histological tumor grade; and increased progesterone receptor (PgR)−, HER2+, and triple negative tumors than patients who had given birth less recently or not at all. Group A patients had significantly shorter survival times than patients in both groups C and N (log rank test; p < 0.001). After adjusting for tumor characteristics, the hazard ratio for death in group A was 2.19 compared with group N ( p = 0.036), and the adjusted hazard ratio restricted to patients in group A with hormone-receptor-positive, and HER2− tumors was 3.07 ( p = 0.011). Young breast cancer patients who had given birth more recently had tumors with more aggressive features and worse prognoses compared with patients who had given birth less recently or were nulliparous. [ABSTRACT FROM AUTHOR]

Myelodysplastic syndrome (MDS) is a heterogeneous group of clonal hematopoietic stem cell diseases. It has been reported that several autoimmune diseases are associated with MDS. Recently, the co-occurrence of MDS with trisomy 8 and rare disorders of the immune system, such as Behçet's disease (BD), has been described. Prognosis in the older-onset group of MDS-associated BD is unfavorable. Here, we report a case of MDS-associated intestinal BD treated successfully by azacitidine therapy. A 59-year-old Japanese male suffering from recurrent high fever, melena, and oral and genital ulcerations was diagnosed with MDS with trisomy 8 and intestinal BD by endoscopic and bone marrow examinations. Immunosuppressive therapies, including infliximab, were ineffective. Due to his severe emphysema, the patient was considered ineligible for stem cell transplantation, and azacitidine therapy was initiated. With the exception of fever, the symptoms of intestinal BD improved, and severe malnutrition and anemia were ameliorated. Fluorescence in situ hybridization analyses of the bone marrow before the eighth cycle revealed that the trisomy 8 had not decreased. To our knowledge, this is the first report of azacitidine therapy for MDS-associated BD. We suggest that azacitidine may control intestinal BD by mechanisms other than those responsible for its effect in MDS. [ABSTRACT FROM AUTHOR]

Background: Several clinical trials of chemotherapy for non-small-cell lung cancer (NSCLC) have been conducted to date. However, these studies have not been effective at identifying category 1 recommended strategies for systemic chemotherapy according to the National Comprehensive Cancer Network clinical practice guidelines. Purpose and Method: To investigate the factors that influence the efficacy and safety of add-on combination chemotherapy for NSCLC based on published reports, we searched the PubMed and EMBASE for reports of randomized, controlled trials that compared efficacy and safety between groups with and without the use of add-on drugs to base chemotherapy in patients with NSCLC. For all the selected articles, we systematically retrieved and assessed the full published report. Results: Of the 753 citations yielded by the electronic search, 82 comparison pairs from 76 articles were selected. The logistic regression analysis showed the second- or third-line treatment for target patients (Line2_3), dose modification of the base drug(s) in the investigational arm, characteristics of the add-on drug, and the number of total combination drugs that had negative coefficients, and the percent of patients with performance status 2 who had positive coefficients for efficacy. For safety, Line2_3, and the percent of female patients had positive coefficient. Conclusions: The present results indicate that the following points are important when investigating new regimen for add-on combination chemotherapy: (1) the number of total combination drugs should be reduced if at all possible; (2) an add-on drug should be noncytotoxic and should not necessitate dose modification (reduction) of the base drug(s). [ABSTRACT FROM AUTHOR]

Posterior reversible encephalopathy syndrome (PRES) has been reported in childhood leukemia patients increasingly frequently. However, the development of PRES in adult leukemia patients during chemotherapy is very rare. We present a case of PRES in an adult patient with acute lymphoblastic leukemia (ALL) after remission induction chemotherapy. A 28-year-old woman with ALL was administered remission induction chemotherapy consisting of cyclophosphamide, daunorubicin, vincristine, prednisone, and l-asparaginase. After initiation of chemotherapy, the patient developed paralytic ileus and hypertension, and on day 30, she suddenly developed generalized convulsions, loss of visual acuity, and muscle weakness in the legs. Magnetic resonance imaging findings and her signs and symptoms were typical of PRES. The symptoms gradually improved following treatment with an anticonvulsant and an antihypertensive agent, and the patient underwent allogeneic bone marrow transplantation. She has completely recovered from PRES and has been asymptomatic without leukemia relapse. During remission induction chemotherapy for ALL, PRES may be caused by multiple drugs, such as l-asparaginase, vincristine, and corticosteroids, with different mechanisms of action. PRES should be recognized as an important complication, which will occur more frequently with the increased intensity of chemotherapy for adult ALL patients. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the efficacy and safety of FOLFOX4 using 'wait and go' strategy in treating metastatic colorectal cancer. Methods: The conventional FOLFOX4 was repeated every 2 weeks. We waited until the recovery of symptoms from persistent neurotoxicity within an added period of 2 weeks, before performing the next cycle ('wait and go' strategy). Results: We enrolled 58 patients, in whom a total of 481 cycles were administered (median 8 per patient; range 1-16). Toxicity was evaluated in 58 patients and response in 55. The major toxic effect was grade 3/4 neutropenia (33%). Painful paresthesia or persistent functional impairment was observed in 4 patients (7%). The response rate was 40% (95% confidence interval; 27.1-52.9%). The median progression-free survival time was 10.2 months, the 1-year survival rate was 89%, and the median overall survival time was 27.6 months. Conclusions: These findings indicate that this 'wait and go' strategy reduces the frequency of persistent neuropathy while maintaining efficacy against metastatic colorectal cancer. [ABSTRACT FROM AUTHOR]

Background: The number of industry-sponsored global clinical trials conducted in Asian countries has been increasing in recent years as part of the global development of new drugs. A successful global clinical trial in Asia depends on formulating a development strategy based on a thorough understanding of the preceding study results and the characteristics of individual countries within the region. In addition, large population sizes and the simple constitution of ethnicity that is seen in all Asian countries are a great advantage to achieve an adequate sample size and shorten the study period. The purpose of this paper is to analyse the current state of industry-sponsored global clinical trials in Asian countries. Methods: Clinical trial information was compiled by extracting relevant information from ClinicalTrials.gov to create a secondary database of all industry-sponsored, phase II and III studies that involved two of more Asian countries. Country-specific analyses were conducted for study design (e.g. type, phase, target sample size, sponsor's nationality, and time of commencement), therapeutic area and target disease. Results: The majority of global clinical trials involving Asian countries were confirmatory in nature, as shown by their basic study designs and study phases; however, exploratory studies are more common than confirmatory studies in Japan and Singapore. The most common target disease was non-small-cell lung cancer, followed by breast cancer, bipolar disorder, type 2 diabetes mellitus and hepatitis B. Industry-sponsored global clinical trials in Asia covered a variety of therapeutic areas; however, therapeutic areas vary greatly among countries. Cardiovascular diseases ranked highly in China, and HIV infections ranked first in Thailand. Conclusion: Differences in study designs observed across the Asian region may reflect country-specific characteristics; for example, Singapore is actively inviting early phase clinical studies, while Japan has been originating a number of new drugs. Industry-sponsored global clinical trials in Asia have recently covered a variety of therapeutic areas. There are, however, some different trends in the target diseases among different countries. It is thus crucial to consider these trends when selecting study areas and formulating a development strategy, to conduct a global clinical trial in Asian countries more efficiently and effectively. [ABSTRACT FROM AUTHOR]

Background: In Japan, the launch of new drugs is often delayed compared with other major regions, including the US and European countries. This so-called 'drug lag' is a significant problem because patients are being denied access to new and potentially life-saving therapies. Methods: Key performance indicators were compared between Japanese and non-Japanese clinical trials conducted between 2002 and 2007. Metrics included human resources involvement, performance of monitors and clinical study sites, and completion times. Clinical studies all involved the macrolide antibacterial, azithromycin extended-release for the treatment of community-acquired pneumonia (CAP), which was selected because there are no major regional differences in the diagnosis and evaluation criteria of CAP. Results: The results show that, although the data quality in Japan was better than that in other countries, the performance of monitors and clinical study sites was lower. The number of enrolled patients per site was 2- to 3-fold greater in other countries compared with Japan. Conclusions: Improvements in the conduct of clinical trials in Japan could be achieved by concentrating on high performance clinical study sites and key performance indicators should continue to be assessed during such studies to ensure the selected sites remain competitive. Alternatively, Japanese researchers could focus on studies that require more elaborate management and relatively few patients, such as early-phase, proof of concept studies. [ABSTRACT FROM AUTHOR]

The article evaluates a phase III study that examines the efficacy of gefitinib and docetaxel in the survival of Japanese patients with non-small-cell lung cancer who received previous treatment with platinum doublets. It discusses the reasons for the differences in the effects of molecular-targeted drugs and cytotoxic antineoplastic agents observed in this study. It highlights the magnitude of the antitumor activity of these two different categories of drugs.

The aim of this study was to develop a prediction model using serum tumor markers to predict the response to chemotherapy of patients with metastatic or recurrent breast cancer. We retrospectively analyzed a training set of 105 patients with metastatic or recurrent breast cancer. Their chemotherapeutic response had been evaluated according to the World Health Organization (WHO)’s response criteria. Our model for predicting response using carcinoembryonic antigen (CEA), carbohydrate antigen (CA) 15-3, and NCC-ST-439 was determined using the area under the receiver operating characteristic curve (ROC-AUC) and the overall misclassification rate (OMR) in a random cross-validation. The prediction model was then verified in a consecutive set of 64 patients. Their response had been evaluated using the response evaluation criteria in solid tumors (RECIST) criteria. The best prediction model consisted of the serum CEA, CA15-3, and NCC-ST-439 levels, but the prediction formula varied according to the baseline CA15-3 level (elevated or normal). The overall ROC-AUC and OMR in the training set were 0.83 and 0.19, respectively. The overall ROC-AUC and OMR in the verification set were 0.72 and 0.28, respectively. When the verification set was stratified according to either the objective response or the predicted response, the time-to-progression, but not the overall survival, was significantly different. Our model for predicting the response to first-line chemotherapy of patients with metastatic or recurrent breast cancer may be valid because it predicted the outcome of more than 70% of the patients in an independent verification set. [ABSTRACT FROM AUTHOR]

To evaluate whether [F-18] fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) can distinguish benign from malignant solitary pulmonary nodules (SPNs) with non-solid components. [F-18] FDG-PET/CT scans were performed on 53 consecutive patients (30 men, 23 women; mean age 65 years) who had SPNs with non-solid components identified by CT screening for lung cancer. All patients underwent surgical resection, and all lesions were pathologically proved. Visual score, maximal, and mean standardized uptake value (SUV), and maximal and mean lesion-to-normal tissue count density ratio (LNR) were calculated in all lesions. In addition, clinical characteristics, laboratory test results, and CT findings were assessed. Benign SPNs with non-solid components had a higher uptake on [F-18] FDG-PET/CT. Visual score, maximal and mean SUV, and maximal and mean LNR were significantly higher in the benign when compared with the malignant SPNs ( P < 0.001). When the cutoff of 1.5 was assigned for maximal SUV, the diagnostic performance of [F-18] FDG-PET/CT in predicting benign SPN revealed 100.0% sensitivity, 96.4% specificity, and 100.0% accuracy. [F-18] FDG-PET/CT is useful for the differential diagnosis of SPNs with non-solid components. [ABSTRACT FROM AUTHOR]

There is some unknown reason Ewing family of tumors (EFTs) is much less common on Asia and Africa than in the Western Caucasian population. This study analyzed the prediction of response and prognostic factors for Ewing family of tumors (EFTs) in an Asian population with a low incidence. We retrospectively reviewed 94 patients with EFTs between 1978 and 2006. Fifteen patients received local therapy only. Statistical analyses were performed for 79 patients, including those who received systemic chemotherapy, to identify factors related to chemotherapy responsiveness, event-free survival, and overall survival. Of the 79 patients whose records were analyzed, the 5-year event-free rate and overall survival (OS) rate were 41 and 54%, respectively. The response rate to first-line chemotherapy was 61% in 70 patients with assessable lesions. A significant predictor of response was existence of a non-pelvic primary tumor ( P = 0.04). Significant prognostic factors for OS were age, performance status, and metastases at the time of diagnosis ( P < 0.01, respectively). Fifty-four patients had disease progression or recurrence after first-line treatment. The time to progression was 3.4 months after salvage treatment. Progression during first-line treatment was significantly associated with time to progression after salvage treatment ( P = 0.01). All patients treated without chemotherapy in first-line treatment were recurred with poor prognosis. A non-pelvic primary tumor was a favorable predictor of responsiveness to chemotherapy. Chemo-resistant patients might less benefit from second line chemotherapy. Chemotherapy in first-line treatment should not be omitted, even if primary tumor was extirpated completely. [ABSTRACT FROM AUTHOR]

Hormone replacement therapy (HRT) has been considered one of the main risk factors for breast cancer. Studies demonstrating the relationship between HRT and breast cancer incidence were conducted in Western countries and the target populations were mainly Caucasians. Since the Women’s Health Initiatives demonstrated that HRT increased the risk of breast cancer with statistical significance, the number of HRT users in the United States has dramatically decreased. A recent case-control study has investigated the relationship between HRT and breast cancer in Japan, and here we review the results of this study to compare any discrepancy in breast cancer risk between Japanese and Western populations. For this case-control study, at seven institutions, women between the ages of 45 through 69 years, with histologically confirmed breast cancer, were selected as the case group. An age-adjusted control group was selected, using hospital-based data, including records of those screened for lung, gastrointestinal, and gynecological cancer. Questionnaires were administered, and items questioned included various factors related to the incidence of breast cancer: age at diagnosis, body mass index (BMI), smoking habit, age at menopause, birth history, number of births, number of children, history of breast feeding, familial background, and menopausal status. In total, 6183 samples (98.4% of the estimated samples) were put into the database. Data from 276 samples were excluded due to ineligibility. Finally, 5861 samples (3434 cases and 2427 controls) were analyzed. In 3316 cases, 164 (5.0%) patients received hormone-replacement therapy (HRT); on the other hand, 253 (10.7%) of 2355 controls received HRT. The odds ratio was 0.432 (95% confidence intervals [CI], 0.352–0.53), and there was a significantly negative correlation between HRT use and breast cancer. The risk factors in Japanese women showed similar profiles to those in women in Western countries. However, we did find some different profiles of breast cancer risk in the Japanese women. Changing of lifestyle may increase breast cancer risk in Japan. [ABSTRACT FROM AUTHOR]

A letter to the editor discussing variuos clinical manifestations of acute myocarditis is presented.

The original version of this article contained a mistake in Table 5. Correct version is presented here. [ABSTRACT FROM AUTHOR]

The correct name of the twelfth author should be ‘‘Yasuhiro Yuasa”, and not ‘‘Yasuhiko Yuasa’’ as given in the original publication of the article. [ABSTRACT FROM AUTHOR]