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The first space-based Doppler wind lidar (DWL) onboard the Aeolus satellite was launched by the European Space Agency (ESA) on 22 August 2018 to obtain global profiles of horizontal line-of-sight (HLOS) wind speed. In this study, the Raleigh-clear and Mie-cloudy winds for periods of baseline 2B02 (from 1 October to 18 December 2018) and 2B10 (from 28 June to 31 December 2019 and from 20 April to 8 October 2020) were validated using 33 wind profilers (WPRs) installed all over Japan, two ground-based coherent Doppler wind lidars (CDWLs), and 18 GPS-radiosondes (GPS-RSs). In particular, vertical and seasonal analyses were performed and discussed using WPR data. During the baseline 2B02 period, a positive bias was found to be in the ranges of 0.46–1.69 m s−1 for Rayleigh-clear winds and 1.63–2.42 m s−1 for Mie-cloudy winds using the three independent reference instruments. The biases of Rayleigh-clear and Mie-cloudy winds were in the ranges of −0.82−+0.45 m s−1 and −0.71−+0.16 m s−1 during the baseline 2B10 period, respectively. The systematic error for the baseline 2B10 was improved as compared with that for the baseline 2B02. The vertical analysis using WPR data showed that the systematic error was slightly positive in all altitude ranges up to 11 km during the baseline 2B02 period. During the baseline 2B10 period, the systematic errors of Rayleigh-clear and Mie-cloudy winds were improved in all altitude ranges up to 11 km as compared with the baseline 2B02. Immediately after the launch of Aeolus, both Rayleigh-clear and Mie-cloudy biases were small. Within the baseline 2B02, the Rayleigh-clear and Mie-cloudy biases showed a positive trend. For the baseline 2B10, the Rayleigh-clear wind bias was generally negative at all months except August 2020, and Mie-cloudy wind bias gradually fluctuated. The systematic error was close to zero with time in 2020 and did not show a marked seasonal trend. The dependence of the Rayleigh-clear wind bias on the scattering ratio was investigated, showing that the scattering ratio had a minimal effect on the systematic error of the Rayleigh-clear winds during the baseline 2B02 period. On the other hand, during the baseline 2B10 period, there was no significant bias dependence on the scattering ratio. Without the estimated representativeness error associated with the comparisons using WPR observations, the Aeolus random error was determined to be 6.71 (5.12) and 6.42 (4.80) m s−1 for Rayleigh-clear (Mie-cloudy) winds during the baseline 2B02 and 2B10 periods, respectively. The main reason for the large random errors is probably related to the large representativeness error due to the large sampling volume of the WPRs. Using the CDWLs, the Aeolus random error estimates were in the range of 4.49–5.31 (2.93–3.19) and 4.81–5.21 (3.30–3.37) m s−1 for Rayleigh-clear (Mie-cloudy) winds during the baseline 2B02 and 2B10 periods, respectively. By taking the GPS-RS representativeness error into account, the Aeolus random error was determined to be 4.01 (3.24) and 3.02 (2.89) m s−1 for Rayleigh-clear (Mie-cloudy) winds during the baseline 2B02 and 2B10 periods, respectively.

A phase II trial was conducted to investigate the benefit of oxaliplatin-based adjuvant chemotherapy in Japanese stage III colon cancer patients. Eligible patients were scheduled to receive 12 cycles of mFOLFOX6 or 8 cycles of CAPOX in adjuvant settings. The primary endpoint was the 3-year disease-free survival (DFS). Cox proportional hazards regression was performed to identify risk factors for a worse DFS. A total of 130 patients, including 73 patients receiving mFOLFOX6 and 57 patients receiving CAPOX, were enrolled from 16 institutions between April 2010 and April 2014. The 3-year DFS was 82.2%, exceeding the expected primary endpoint of 81.7%. The 3-year DFS tended to be higher in patients receiving mFOLOFOX6 than in those receiving CAPOX (mFOLFOX6, 86.3%; CAPOX, 76.9%; P = 0.06). The 3-year DFS rates did not differ markedly based on the risk stratification (T1/T2/T3 N1 vs. T4 or N2) indicated by the IDEA COLLABORATION study (P = 0.22). In the multivariate analysis, stage IIIC (P = 0.046) and early discontinuation (P

Background: The current pooled analysis evaluated the efficacy of Hangeshashinto (TJ-14) in the prevention and/or treatment of chemotherapy-induced oral mucositis (COM) in gastric cancer and colorectal cancer using two prospective, multi-institutional, randomized, double-blind, placebo-controlled phase II trials. Patients and Methods: HANGESHA-G and HANGESHA-C randomly assigned patients with gastric cancer or colorectal cancer who developed moderate to severe COM (grade ≥1) during any cycle of chemotherapy to receive either TJ-14 or a placebo as a double-blind trial. The patients received a placebo or TJ-14 for four to six weeks, according to the chemotherapy regimen, from the start of their next course of chemotherapy. The primary endpoint was the incidence of grade ≥2 COM in the protocol treatment course, and the secondary endpoints were the time to disappearance of COM and the incidence of adverse events. Results: The pooled population included 181 patients. The incidence of grade ≥2 COM in the TJ-14 group was 55.7% (49 patients), while that in the placebo group was 53.8% (50 patients); there was no significant difference between the two groups (p=0.796). The median time to remission of grade ≥2 COM to grade

Purpose Hangeshashinto (TJ-14, a Kampo medicine), which reduces the level of prostaglandin E2 and affects the cyclooxygenase activity, alleviates chemotherapy-induced oral mucositis (COM). We conducted a double-blind, placebo-controlled, randomized comparative trial to investigate whether TJ-14 prevents and controls COM in patients with colorectal cancer. Methods Ninety-three patients with colorectal cancer who developed moderate-to-severe COM (WHO grade ≧1) during any cycle of chemotherapy using FOLFOX, FOLFIRI, and/or XELOX treatment were randomly assigned to receive either TJ-14 (n = 46) or placebo (n = 47). Patients received the administration of placebo or TJ-14 for 2 weeks at the start of the next course of chemotherapy. Patients were assessed three times per week for safety and for COM incidence and its severity using the WHO grading. Results Ninety eligible patients (TJ-14; 43, placebo; 47) per protocol set analysis were included in the analysis after the key-opening. Although the incidence of grade ≧2 oral mucositis was lower for patients treated with TJ-14 compared to those treated with placebo, there was no significant difference (48.8 vs. 57.4 %; p = 0.41). The median duration of grade ≧2 mucositis was 5.5 versus 10.5 days (p = 0.018). No difference in other treatment toxicity was observed between the two groups, and patients exhibited high compliance in dosing administration. Conclusion The present study results did not meet the primary endpoint. However, TJ-14 demonstrated a significant effect in the treatment of grade ≧2 mucositis in patients with colorectal cancer compared to the placebo.

The aim of this multicenter, open-label, randomized phase II trial was to evaluate the efficacy of a dose-dense capecitabine and oxaliplatin (XELOX) regimen in patients with metastatic colorectal cancer (mCRC) for whom reintroduction of oxaliplatin had been planned as a third- or later-line regimen.The patients with mCRC who had received prior chemotherapy including oxaliplatin and were scheduled for reintroduction of oxaliplatin were randomized to capecitabine (1,000 mg/m(2)) twice daily on days 1-14 and oxaliplatin (130 mg/m(2)) on day 1 every 21 days (Q3W group) or capecitabine (2,000 mg/m(2)) twice daily on days 1-7 and oxaliplatin (85 mg/m(2)) on day 1 every 14 days (Q2W group). The primary endpoint was the time-to-treatment failure (TTF). Other endpoints included overall survival (OS), progression-free survival (PFS) and other adverse events (AEs).A total of 46 patients were enrolled in the trial-22 patients were randomly assigned to the Q3W group and 23 to the Q2W group. The median TTF was 3.4 months in both groups (hazard ratio [HR] 1.053; p = 0.880). The median PFS and OS were 3.3 and 9.2 months in the Q2W group and 4.3 and 12.1 months in the Q3W group, respectively (HR 1.15; p = 0.153 and 0.672; p = 0.836). The most common grade 3-4 AEs in the Q3W and Q2W groups were fatigue (27.3 vs 21.7), neuropathy (9.1 vs 0 %) and diarrhea (9.1 vs 0 %), respectively.There was no significant inter-group difference in any of the efficacy and safety endpoints, including TTF, OS, RFS and AEs. The results of this clinical trial were convincingly negative.

Aim: ML18147 showed continued bevcizumab(BEV) with second-line chmotherapy for patients with metastatic colorectal cancer (mCRC) treated with bev plus standard first-line chemotherapy, represents an option for patients with mCRC independent of KRS status. EAGLE study evaluted two doses of bev (10 mg/kg or 5 mg/kg) combined with FOLFIRI in the second-line setting after first-line treatmet with bev plus oxaliplatin-based therapy. Bev 10 mg/kg plus FOLFIRI as second-line treatment did not prolong pogression-free survival (PFS) compared with bev 5mg/kg plus FOLFIRI in patients with mCRC. Methods: Outcomes according to tumor KRAS status were evaluated as an exploratory analysis. KRAS data were collected from each institution. Survival analyses using Cox regression and Log-rank test were conducted by subgroups of the KRAS status. Results: Of 387 patients, 326 (84%) had KRAS data; 164 (50%) had KRAS wild-type tumors and 162 (50%) had mutant KRAS tumors. The median PFS was 7.1 months for bev 10 mg/kg and 5.9 months for bev 5 mg/kg (P = 0.568; HR = 1.04; 95% confidence interval (CI) : 0.76-1.43) for wild-type KRAS and 5.6 months fo bev 10 mg/kg and 6.5 months for bev 5mg/kg, respectively ( P = 0.89; HR = 1.10; 95% CI: 0.80-1.51) for mutant KRAS. The P value of test for treatment-subgroup inteaction was 0.956. The median overall survival (OS) was 17.9 months for bev 10mg/kg and 15.5 months for bev 5 mg/kg, respectvely (P = 0.244; HR = 0.80; 95% CI : 0.55-1.17) for wild-tpe KRAS and 15.9 months for bev 10 mg/kg versus 17.7 months for bev 5 mg/kg, respectivly (P = 0.312; HR = 1.21; 95% CI 0.84-1.74) for mutant KRAS. Conclusions: Although possible differences of treatment effect between bev 5 mg/kg and 10 mg/kg groups were observed for patients with wild-type KRAS, these results revealed bev 10mg/kg plus FOLFIRI as second-line treatment did not prolong PFS compared with bev 5 mg/kg plus FOLFIRI in patients with mCRC depending on KRAS status. Disclosure: S. Iwamoto: I have honoraria to disclose from Chugai, MerckSerono; T. Takahashi: I have honoraria to disclose from Chugai, Takeda, Taiho, MerckSerono. Bristol-Meyers Squibb; T. Kato: I have honoraria to disclose from Chugai, Yakult; T. Denda: I have honoraria to disclose from Taiho, Lilly, Sanofi; H. Baba: I have honoraria to disclose from Chugai, Takeda, Taiho; H. Mishima: I have honoraria to disclose from Chugai, Takeda, Taiho, Yakult. Ono, Tsumura, MerckSerono. Bristol-Meyers Squibb, Medicon. All other authors have declared no conflicts of interest.

Background and aims Although chemotherapy-induced oral mucositis (COM) is a common side effect of many anticancer therapies, the optimal treatment for this condition is not well established. Recent studies showed that one of the traditional Japanese herbal medicines (Kampo) called TJ-14 (hangeshashinto) may be useful for COM via downregulating pro-inflammatory prostaglandins in the cyclooxygenase pathway (ASCO-GI2011, AGA2012). The efficacy of TJ-14 for the prevention and/or treatment of COM was exploratively tested in a randomized, double-blind, placebo-controlled trial in colorectal cancer patients. Methods Ninety-three patients who developed COM during FOLFOX, FOLFIRI or XELOX treatment for advanced colorectal cancer were centrally randomized to receive either a topical application of TJ-14 or placebo. Patients were advised to dissolve 2.5 g of TJ-14 or placebo in 50 mL of tap water and rinse their oral cavity three times daily for 10 seconds with the solution before expectorating it. Patients followed this oral care throughout the treatment before the next course of chemotherapy began. The COM grade was evaluated using the Common Terminology Criteria for Adverse Events (CTCAE) version 4 and a self-administered questionnaire before and after the 2-week treatment with the TJ-14 or placebo solution. The study endpoints included the incidence of worst grade COM, the incidence of grade 2 or higher COM, the duration of grade 2 or higher COM, and the healing time of COM. Results Ninety patients (43 in the TJ-14 group, 47 in the placebo group) were included in the statistical analysis. The incidence of grade 3 COM was 9.5% vs. 17%, while no significant difference in the incidence of grade 2 or higher COM was found between the two groups. The median duration of grade 2 or higher COM was 5.5 days vs. 10.5 days (p = 0.018). No significant difference was observed between the two groups with regard to the incidence of grade 2 or higher adverse events. Conclusions Topical TJ-14 rinse appears to have a significant ability to treat grade 2 or higher COM and reduce the risk of developing grade 3 COM. Our results are encouraging and warrant further phase III trials. Disclosure All authors have declared no conflicts of interest.