Effect of comprehensive cancer genomic profiling on therapeutic strategies and clinical outcomes in patients with advanced biliary tract cancer: A prospective multicenter study.

Characterization of the genomic landscape of biliary tract cancer (BTC) may lead to applying genotype-matched therapy for patients with this disease. Evidence that comprehensive cancer genomic profiling (CGP) guides genotype-matched therapy to improve clinical outcomes is building. However, the significance of CGP in patients with BTC remains unclarified in clinical practice. Therefore, the purposes of this study were to assess the utility of CGP and identify associations between clinical outcomes and genomic alterations in patients with BTC. In this prospective analysis, detection rates for actionable genomic alterations and access rates for genotype-matched therapy were analyzed in 72 patients with advanced BTC who had undergone commercial CGP. Cox regression analyses assessed relationships between overall survival and genomic alterations detected with CGP. The most common genomic alterations detected were TP53 (41, 56.9%), followed by CDKN2A/B (24, 33.3%/20, 27.8%), and KRAS (20, 27.8%). Actionable genomic alterations were identified in 58.3% (42/72) of patients. Detection rates for FGFR2 fusions, IDH1 mutations, and BRAF V600E were low in this cohort. Eight (11.1%) patients received genotype-matched therapy. For patients with intrahepatic cholangiocarcinoma (ICC), CDKN2A/B loss was associated with shorter overall survival. These real-world data demonstrate that CGP can identify therapeutic options in patients with advanced BTC. CDKN2A/B loss was identified as a poor prognostic factor in patients with ICC. Thus, this study provides a rationale for considering CGP in planning therapeutic strategies for advanced BTC.

The efficacy of the Kampo medicine rikkunshito for chemotherapy-induced anorexia (RICH trial): study protocol for a randomized controlled trial.

BACKGROUND: Cisplatin is a key drug in lung cancer therapy. However, cisplatin is also well known to induce gastrointestinal disorders, such as chemotherapy-induced nausea and vomiting, anorexia, and weight loss. These symptoms sometimes affect patients' quality of life and make continuation of chemotherapy difficult. Anorexia is a cause of concern for patients with cancer because a persistent loss of appetite progresses to cancer cachexia. Although evidence-based management for chemotherapy has recently been established, there is room for improvement. METHODS/DESIGN: This placebo-controlled, double-blind, randomized trial will aim to determine the efficacy of the traditional Japanese Kampo medicine rikkunshito (TJ-43) for preventing anorexia caused by cisplatin-including chemotherapy in patients with lung cancer. Patients with lung cancer who plan to receive cisplatin-including chemotherapy will be recruited. Patients who provide written consent will be randomly allocated to receive either TJ-43 (arm A) or placebo (arm B) for one course of chemotherapy (21 or 28 consecutive days). Investigators and patients will be masked to the treatment assignment throughout the trial. The primary endpoint will be evaluated as the change in dietary intake from day 0 (the day before the start of chemotherapy) to day 7 of cisplatin-including chemotherapy. The two arms of the trial will comprise 30 patients each. From November 2014, a total of 60 patients will be recruited, and recruitment for the study is planned to be complete by October 2017. DISCUSSION: This trial is designed to examine the efficacy of rikkunshito (TJ-43) for reducing anorexia and maintaining food intake caused by cisplatin-including chemotherapy in patients with lung cancer. TRIAL REGISTRATION: Japan Pharmaceutical Information Center Clinical Trials Information (JAPIC CTI), trial registration: JAPIC CTI-142747 . Registered on 15 December 2014; the RICH trial.

Immunohistochemical profiling of receptor tyrosine kinases, MED12, and TGF-ßRII of surgically resected small cell lung cancer, and the potential of c-kit as a prognostic marker.

The limited number of available treatments for patients with small-cell lung cancer (SCLC) has prompted us to further investigate the biology of SCLC by molecular profiling. We collected formalin-fixed paraffin-embedded tumor samples from 127 patients with SCLC, who had undergone surgery at 16 institutions between January 2003 and January 2013, and analyzed the association between disease-specific survival and protein expression of c-kit, c-Met, epidermal growth factor receptor, human EGFR-related 2, vascular endothelial growth factor receptor II, anaplastic lymphoma kinase, mediator complex subunit 12 (MED12), and transforming growth factor beta receptor II (TGF-ßRII) by immunohistochemistry (IHC). Of the 125 evaluable samples, all tumors expressed MED12, and 123 samples (98.4%) expressed TGF-ßRII. MED12 was highly expressed in the nucleus in 92% of the positive samples while TGF-ßRII was highly expressed in the cytoplasm in 55% of the positive samples. High c-kit expression was an independent favorable prognostic marker confirmed by multivariate analysis (hazard ratio: 0.543, 95% confidence interval: 0.310-0.953, p = 0.033). Both the relapse free-survival and overall survival of patients who underwent adjuvant chemotherapy were statistically longer in those with high c-kit expression (n = 38) than those with intermediate, low, or no c-kit expression (n = 19) (not reached vs 11.6 months, p = 0.021; not reached vs 25.9 months, p = 0.028). IHC for c-kit may offer a prognostic marker for early-stage SCLC, and the results for MED12 and TGF-ßRII may suggest the biological characteristics of SCLC. Further investigation of the roles of their related molecules in early stage SCLC is required.

Rikkunshito for Preventing Chemotherapy-Induced Nausea and Vomiting in Lung Cancer Patients: Results from 2 Prospective, Randomized Phase 2 Trials.

The herbal medicine rikkunshito has the potential to improve chemotherapy-induced nausea and vomiting (CINV) by stimulating ghrelin secretion. We aimed to evaluate the efficacy and safety of rikkunshito in preventing CINV for patients with lung cancer. Two separate prospective, randomized, phase II parallel design studies were conducted in patients with lung cancer. Fifty-eight and sixty-two patients scheduled to receive highly emetogenic chemotherapy (HEC) and moderately emetogenic chemotherapy (MEC), respectively, were randomized 1:1 to receive either standard antiemetic therapy in accordance with international guidelines (S group) or standard antiemetic therapy plus oral rikkunshito (R group). The primary endpoint was overall complete response (CR)-that is, no emesis and rescue medication in the first 120 h post-chemotherapy. Secondary endpoints included CR in the acute (0-24 h) and delayed (>24-120 h) phases and safety. Fifty-seven patients (S group, 28; R group, 29) receiving HEC and sixty-two patients (S group, 30; R group, 32) receiving MEC with comparable characteristics were evaluated. The CR rates were similar across the S and R groups for the HEC study in the overall (67.9% vs. 62.1%), acute (96.4% vs. 89.6%), and delayed (67.9% vs. 62.1%) phases, respectively, and for the MEC study in the overall (83.3% vs. 84.4%), acute (100% vs. 100%), and delayed (83.3% vs. 84.4%) phases, respectively. No severe adverse events were observed. Although rikkunshito was well tolerated, it did not demonstrate an additional preventative effect against CINV in lung cancer patients receiving HEC or MEC. Clinical Trial Registry Information: This study is registered with the University Hospital Medical Information Network (UMIN) Clinical Trial Registry, identification numbers UMIN 000014239 and UMIN 000014240.