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Purpose: Zoledronic acid (ZOL) is a nitrogen-containing bisphosphonate that induces osteoclast apoptosis and inhibits bone resorption by inhibiting the mevalonate pathway. Its benefit for the prevention of skeletal complications due to bone metastases has been established. However, the antitumor efficacy of ZOL, although suggested by multiple preclinical and clinical studies, has not yet been clinically proven. We performed the present randomized Phase 2 trial to investigate the antitumor effect of ZOL with chemotherapy (CT). Methods: Asian patients with HER2-negative invasive breast cancer were randomly assigned to either the CT or CT+ZOL (CTZ) group. One hundred and eighty-eight patients were randomized to either the CT group (n = 95) or the CTZ group (n = 93) from March 2010 to April 2012, and 180 patients were assessed. All patients received four cycles of FEC100 (fluorouracil 500 mg/m2, epirubicin 100 mg/m2, and cyclophosphamide 500 mg/m2), followed by 12 cycles of paclitaxel at 80 mg/m2 weekly. ZOL (4 mg) was administered three to four times weekly for 7 weeks to the patients in the CTZ group. The primary endpoint was the pathological complete response (pCR) rate, which was defined as no invasive cancer in the breast tissue specimen. Safety was assessed in all patients who received at least one dose of the study drug. Results: This randomized controlled trial indicated that the rates of pCR in CTZ group (14.8%) was doubled to CT group (7.7%), respectively (one-sided chi-square test, p = 0.068), though the additional efficacy of zoledronic acid was not demonstrated statistically. The pCR rate in postmenopausal patients was 18.4% and 5.1% in the CTZ and CT groups, respectively (one-sided Fisher’s exact test, p = 0.071), and that in patients with triple-negative breast cancer was 35.3% and 11.8% in the CTZ and CT groups, respectively (one-sided Fisher’s exact test, p = 0.112). Thus the addition of ZOL to neoadjuvant CT has potential anticancer benefits in postmenopausal patients and patients with triple-negative breast cancer. Further investigation is warranted. Trial Registration: University Hospital Medical Information Network. . [ABSTRACT FROM AUTHOR]

Background: Clinical studies have shown that palbociclib improves progression-free survival in hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) patients with advanced breast cancer (ABC). However, there are insufficient data on its use in a real-world setting in Japan. The aim of this study was to investigate the effectiveness, predictive factors, and safety of palbociclib among Japanese patients in routine clinical practice., Methods: Between December 1, 2017, and April 30, 2019, we recruited patients from 9 hospitals and retrospectively evaluated the data on HR+/HER2- patients with ABC who received palbociclib for at least 1 week. The correlation between time-to-treatment discontinuation (TTD) and clinical background was investigated via univariate and multivariate analyses using Cox hazards models., Results: A total of 177 women were available for analysis. Of these patients, 58 (33%) patients were treated with palbociclib with an aromatase inhibitor and 117 (66%) patients were treated with palbociclib and a selective estrogen receptor degrader. Approximately three-fourths of the patients (n = 130, 73%) received palbociclib as third- or later-line therapy. One-third of the patients had 3 or more metastatic sites (n = 59, 33%), and one-third of the patients had liver metastasis (n = 59, 33%). The median follow-up duration at the time of data cutoff was 8.9 months, the median TTD was 6.3 months, and the median overall survival was not reached. Liver metastasis (hazard ratio [HR]: 1.54 [95% confidence interval {CI}: 1.03-2.27]), high serum lactate dehydrogenase (LDH) level (>300 U/L) (HR: 2.58 [95% CI: 1.49-4.26]), and high neutrophil-to-lymphocyte ratio (NLR) (⩾3.0) (HR: 1.76 [95% CI: 1.13-2.69]) were significantly associated with shorter TTD. The most common hematologic adverse event was neutropenia, which occurred in 93% of the patients., Conclusion: Based on the results of the pivotal phase 3 trials, the median TTD recorded in this study was shorter than expected. Our results suggest that liver metastasis, serum LDH level, and NLR may be predictive factors for HR+/HER2- ABC treatment outcomes., Competing Interests: Declaration of conflicting interests:The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Y.K. received honoraria from Eisai, Novartis, Pfizer, Eli Lilly, Taiho, and Chugai. All other authors declare no conflict of interest., (© The Author(s) 2020.)

A 66-year-old Japanese woman was admitted to our hospital for jaundice. Abdominal computed tomography(CT) showed dilatation of the intra- and extra-hepatic bile duct, and a hypovascular lesion measuring 30mm in diameter in the head of the pancreas. This tumor was in contact with the(superior mesenteric vein: SMV)and(inferior vena cava: IVC), but there were no obvious signs of invasion. Upper gastrointestinal endoscopy showed obstruction of the duodenum. We chose to perform an upfront surgery, considering the patient's general condition being stable and the difficulties associated with endoscopic biliary drainage. During surgery, stiff attachment between the tumor and IVC was identified and wedge resection of the IVC wall was performed. SMV resection and end-to-end reconstruction were also carried out. Pathological studies of the surgical specimen revealed direct invasion by the pancreatic adenocarcinoma into the adventitia of the IVC. The postoperative course was uneventful, and the patient was discharged from the hospital on the 27th postoperative day; she underwent adjuvant chemotherapy(S-1 100mg/day)and is still alive without tumor recurrence, 21 months after surgery. Cases of resected pancreatic adenocarcinoma directly invading the IVC are rare. In this case, pancreaticoduodenectomy along with wedge resection of the IVC wall could safely be performed, and no complications were observed. There is a need for further accumulation of similar cases.

Background/aim: Risk factors for chemotherapy-induced nausea and vomiting (CINV) with anthracycline-containing regimen for breast cancer patients remain unknown. The risk factors for CINV with FEC100 were investigated., Patients and Methods: Data on CINV events and patient backgrounds of 180 patients were collected from the first cycle of FEC100 treatment. In this regimen, patients were administered various antiemetics (ADs). The combinations of ADs were classified into four categories, while body mass index (BMI) was stratified into three categories. Risk factors were selected based on patient characteristics and combination of ADs. Risks for CINV were analyzed by univariate and multivariate analyses., Results: In the univariate analysis of nausea, BMI was a significant factor, while BMI and combination of ADs were significant in vomiting. In the multivariate analysis concerning nausea, BMI was a significant factor. In the analysis concerning vomiting, the combination of ADs and BMI were significant., Conclusion: BMI was the most important risk factor for nausea and vomiting, while the combination of ADs was for vomiting., (Copyright© 2019, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

A 68-year-old woman underwent Miles' surgery with a diagnosis of a rectalgastrointestinalstromaltumor (GIST)in 2004. In 2005 and 2006, she developed liver metastases that were surgically removed, but once again in June 2006, she presented with liver metastasis, and imatinib therapy(400mg/day)was administered. In October 2016, she was diagnosed with progression of liver metastasis, and a tumor in the pancreatic body was identified on a CT scan. The patient was referred to our institution for treatment. We performed right hepatectomy and distalpancreatectomy in January 2017. Immunohistochemically, the recurrent tumor was positive for c-kit and CD34, and the diagnosis of GIST was confirmed. The pathological diagno- sis was a high-risk GIST showing 43mitoses per 50 high-power fields. Imatinib therapy(400mg/day)was administered after surgery. She is currently alive without recurrence.

We evaluated the usefulness of the level of thymidylate synthase(TS)and dihydropyrimidine dehydrogenase(DPD) activity as prognostic factors and indicators for selection of chemotherapy regimens. Between November 1997 and March 1999, fifty-seven patients with stages I - IIIa primary breast cancer were registered. Using recurrence risk categories, they were classified into TAM monotherapy, TAM+oral 5-FU, and TAM+CMF groups(each were standard regimens at the time), and underwent postoperative adjuvant chemotherapy. The relationship between prognosis and the TS level and DPD activity, in addition to conventional risk factors, was examined. The recurrence-free survival time curve showed significant differences when stratified by tumor diameter, ER expression, and TS levels, but not by menopausal status, nodal status, surgical method, p53 expression, DPD activity, or HER2 expression. These results suggest that the TS level is useful as a prognostic factor for breast cancer.