A multicenter Phase II study evaluating the efficacy, safety and pharmacokinetics of trastuzumab emtansine in Japanese patients with heavily pretreated HER2-positive locally recurrent or metastatic breast cancer
Kashiwaba M.,Iwate Medical University |
Ito Y.,The Cancer Institute Hospital of JFCR |
Takao S.,Hyogo Cancer Center |
Doihara H.,Okayama University |
And 4 more authors.
Japanese Journal of Clinical Oncology | Year: 2016
Objective: Trastuzumab emtansine significantly improved progression-free survival and overall survival when compared with lapatinib-capecitabine in pretreated human epidermal growth factor receptor 2-positive advanced breast cancer. However, data in Japanese populations are limited. Methods: In the single-arm Phase II JO22997 study, Japanese patients with human epidermal growth factor receptor 2-positive inoperable locally advanced/recurrent or metastatic breast cancer previously treated with at least one prior chemotherapy regimen for locally advanced/recurrent or metastatic breast cancer and trastuzumab in any setting received 3.6 mg/kg trastuzumab emtansine every 3 weeks until progression, unacceptable toxicity or consent withdrawal. The primary endpoint was Independent Review Committee-assessed objective response rate. Secondary endpoints included progression-free survival, overall survival, safety and pharmacokinetics. Results: The objective response rate in 73 treated patientswas 38.4% (90% confidence interval, 28.8-48.6%), exceeding the prespecified boundary for an objective response rate > 20%. After 6.5 months' median follow-up, median progression-free survival was 5.6 months (95% confidence interval, 4.6-8.2). After 28.9 months' median follow-up, median overall survival was 30.5 months (95% confidence interval 25.2-not reached). Therewere no treatment-related deaths. The most common Grade 3/4 adverse events were thrombocytopenia (22%) and aspartate aminotransferase elevations (14%). Thrombocytopenia did not require platelet transfusion and typically recovered before the next cycle. There were no substantial differences in trastuzumab emtansine or trastuzumab pharmacokinetic parameters between this study and previous data from non-Japanese patients. Conclusions: JO22997 results suggest high activity of trastuzumab emtansine in Japanese patients, a safety profile consistent with previous studies in non-Japanese patients, no new safety signals and no evidence of pharmacokinetic differences between Japanese and non-Japanese populations. These results support trastuzumab emtansine therapy for Japanese patients with chemotherapyand trastuzumab-pretreated human epidermal growth factor receptor 2-positive locally advanced/recurrent or metastatic breast cancer. © The Author 2016. Published by Oxford University Press. All rights reserved.
Koyama M.,The Cancer Institute Hospital of JFCR
Clinical Nuclear Medicine | Year: 2015
ABSTRACT: We report on a 53-year-old woman with osteosarcoma of the skull who underwent radiation therapy for metastatic brain tumor. She had a history of uterine endometrial cancer treated with chemotherapy and surgery 9 years previously. FDG PET/CT for surveillance showed nodular accumulation at the right suprainguinal region and very avid accumulation at the left side of the occipital bone. Bone scan showed increased accumulation at the same portion of the occipital bone. The occipital tumor was surgically removed and diagnosed as radiation-induced osteosarcoma. © 2015 by Lippincott Williams & Wilkins
Awano N.,Red Cross |
Inomata M.,Red Cross |
Kondoh K.,Red Cross |
Satake K.,Red Cross |
And 7 more authors.
Internal Medicine | Year: 2012
Multicentric Castleman's Disease (MCD) is a systemic disease characterized by generalized lymphadenopathy and the proliferation of plasma cells. The development of MCD in a patient with preexisting sarcoidosis has not been previously reported. We herein describe a case of MCD developing in a 78-year-old woman with a 17-year history of sarcoidosis. The patient's serum interleukin-6 (IL-6) levels were only slightly elevated; however, the IL-6 levels in the fluid of both pleural effusion and ascites were markedly elevated. The administration of steroid-pulse therapy and prednisolone was ineffective in treating the MCD, although treatment with tocilizumab proved highly effective. © 2012 The Japanese Society of Internal Medicine.
Koyama M.,The Cancer Institute Hospital of JFCR
Clinical nuclear medicine | Year: 2014
Skeletal metastasis is common in patients with malignancy, but very few patients have acrometastasis, that is, metastasis to the hand or foot. We present 2 cases of acrometastasis from lung cancer where primary and metastatic foci were demonstrated on FDG-PET. The first case involves a 53-year-old man who complained of left foot pain and had osteolytic metastasis in the left calcaneus due to lung adenocarcinoma. True whole-body PET demonstrated lung cancer with calcaneal metastasis. Another case involves a 62-year-old man with large cell carcinoma of the right lung who complained of right wrist pain. Osteolytic metastasis of the hamate was demonstrated on images.
Saad F.,University of Montreal |
Brown J.E.,University of Leeds |
Van Poznak C.,University of Michigan |
Ibrahim T.,Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori |
And 12 more authors.
Annals of Oncology | Year: 2012
Background: Osteonecrosis of the jaw (ONJ) has been reported in patients receiving bisphosphonates for metastatic bone disease. ONJ incidence, risk factors, and outcomes were evaluated in a combined analysis of three phase III trials in patients with metastatic bone disease receiving antiresorptive therapies. Patients and methods: Patients with bone metastases secondary to solid tumors or myeloma were randomly assigned to receive either s.c. denosumab (120 mg) or i.v. zoledronic acid (4 mg) every 4 weeks. On-study oral examinations were conducted by investigators at baseline and every 6 months. Oral adverse events were adjudicated by an independent blinded committee of dental experts. Results: Of 5723 patients enrolled, 89 (1.6%) patients were determined to have ONJ: 37 (1.3%) received zoledronic acid and 52 (1.8%) received denosumab (P = 0.13). Tooth extraction was reported for 61.8% of patients with ONJ. ONJ treatment was conservative in >95% of patients. As of October 2010, ONJ resolved in 36.0% of patients (29.7% for zoledronic acid and 40.4% for denosumab). Conclusions: In this combined analysis of three prospective trials, ONJ was infrequent, management was mostly conservative, and healing occurred in over one-third of the patients. Educating physicians about oral health before and during bone-targeted therapy may help reduce ONJ incidence and improve outcomes. © The Author 2011. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved.