Early adverse events after the first administration of zoledronic acid in Japanese patients with osteoporosis

2021 ◽  
Author(s):  
Junichi Takada ◽  
Kousuke Iba ◽  
Osamu Yamamoto ◽  
Takayuki Dohke ◽  
Akira Saito ◽  
...  
Keyword(s):  
Zoledronic Acid ◽  
Adverse Events ◽  
Japanese Patients

scholarly journals AB0249 SAFETY OF BARICITINIB IN JAPANESE PATIENTS WITH RHEUMATOID ARTHRITIS (RA): THE 2020 INTERIM REPORT FROM ALL-CASE POST MARKETING SURVEILLANCE IN CLINICAL PRACTICE

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 1150.1-1150
Author(s):  
T. Fujii ◽  
T. Atsumi ◽  
N. Okamoto ◽  
N. Takahashi ◽  
N. Tamura ◽  
...  
Keyword(s):  
Clinical Practice ◽  
Adverse Events ◽  
Aspiration Pneumonia ◽  
Japanese Patients ◽  
Research Support ◽  
Serious Adverse Events ◽  
Chugai Pharmaceutical ◽  
Post Marketing Surveillance ◽  
Otsuka Pharmaceutical ◽  
Post Marketing

Background:An all-case post marketing surveillance (PMS) of baricitinib (Bari), that started in Sep 2017, collects safety and effectiveness for the first 24 wks of treatment and continues to collect serious adverse events (SAEs) for 3 yrs.Objectives:To evaluate Bari safety in RA patients (pt) in clinical practice.Methods:We report pt baseline demographics and adverse events (AEs) up to 24 wks for pts whose case report files for 24-wk data were completed as of Jun 2020.Results:Data from 3445 pts were analyzed (females=80%, mean age=64yr, mean RA duration 12yr). Bari dose regimen was as follows: 4mg, 60%, 2mg, 27%, 4mg→2mg, 5%, 2mg→4mg, 5%, and others, 2%. Concomitant use of MTX and glucocorticoid was 65% and 48%, respectively. 74% continued treatment for 24 wks. AE and SAE were recognized in 887 (26%) and 122 pts (4%), respectively. 6 pts died of pneumonia, aspiration pneumonia, bacterial pneumonia, cerebral infarction/ILD/aspiration pneumonia, adenocarcinoma, and colorectal cancer. Major AEs were as follows: herpes zoster=3%, liver dysfunction=3%, serious infection=1%, anemia=1%, hyperlipidemia=1%, malignancy=0.3%, interstitial pneumonia=0.2%, MACE=0.1%, and VTE=0.1%.Conclusion:Data do not show new safety concerns and encourage guideline-compliant use of Bari.Disclosure of Interests:Takao Fujii Speakers bureau: Chugai Pharmaceutical Co. Ltd.; Eisai Co. Ltd; Eli Lilly Japan K.K.; Janssen Pharmaceutical K.K.; Ono Pharmaceutical Co. Ltd., Consultant of: Asahikasei Pharma Corp, Grant/research support from: Asahikasei Pharma Corp; AbbVie Japan GK; Chugai Pharmaceutical Co. Ltd., Eisai Co. Ltd; Eli Lilly Japan K.K.; Mitsubishi-Tanabe Pharma Co.; Ono Pharmaceutical Co., Ltd., Tatsuya Atsumi Speakers bureau: AbbVie Japan GK; Astellas Pharma Inc.; Bristol-Myers Squibb Co. Ltd; Chugai Pharmaceutical Co. Ltd.; Daiichi Sankyo Co. Ltd.; Eisai Co. Ltd.; Eli Lilly Japan K.K.; Mitsubishi Tanabe Pharma Co.; Pfizer Japan Inc.; Takeda Pharmaceutical Co. Ltd., UCB Japan Co. Ltd., Consultant of: AbbVie Japan GK; AstraZeneca plc.; Boehringer Ingelheim Co. Ltd.; Medical & Biological Laboratories Co. Ltd.; Novartis Pharma K.K.; Ono Pharmaceutical Co. Ltd.; Pfizer Japan Inc., Grant/research support from: Astellas Pharma Inc., Alexion Inc.; Chugai Pharmaceutical Co. Ltd., Daiichi Sankyo Co. Ltd., Mitsubishi Tanabe Pharma Co., Otsuka Pharmaceutical Co., Ltd.Pfizer Japan Inc.; Takeda Pharmaceutical Co. Ltd., Nami Okamoto Speakers bureau: AbbVie Japan GK; Asahikasei Pharma Co.; AYUMI Pharmaceutical Co.Eisai Co. Ltd; Bristol-Myers Squibb Co. Ltd.; Eli Lilly Japan K.K.; Mitsubishi-Tanabe Pharma Co.; Pfizer Japan Inc.Sanofi K.K.; Chugai Pharmaceutical Co. Ltd.; Novartis Pharma Co.; Teijin Pharma Ltd.; Torii Pharmaceutical Co., Ltd., Nobunori Takahashi Speakers bureau: AbbVie Japan GK; Eisai Co. Ltd.; Mitsubishi Tanabe Pharma Co.; Pfizer Japan Inc.; Chugai Pharmaceutical Co., Ltd.; Eli Lilly Japan K.K.; Janssen Pharmaceutical K.K.; UCB Japan Co. Ltd.; Astellas Pharma Inc.; Bristol Myers Squibb Co. Ltd., Grant/research support from: Bristol Myers Squibb Co. Ltd., Naoto Tamura Speakers bureau: AbbVie Japan GK; Bristol Myers Squibb Co. Ltd.; Chugai Pharmaceutical Co. Ltd.; Eisai Co. Ltd.; Eli Lilly Japan K.K.; Glaxo Smith Kline K.K.; Janssen Pharmaceutical K.K.; Mitsubishi-Tanabe Pharma Co.; Novartis Pharma Co., Atsuo Nakajima: None declared, Ayako Nakajima Speakers bureau: AbbVie Japan GK; Actelion Pharmaceuticals Japan Ltd., Asahi Kasei Pharma Co., Astellas Pharma Inc., Ayumi Pharmaceutical Co., Bristol Myers Squibb Co., Ltd.,Chugai Pharmaceutical Co., Ltd., Eisai Co., Ltd., Eli Lilly Japan K.K., Glaxo Smith Kline K.K., Hisamitsu Pharmaceutical Co. Inc., Kyorin Pharmaceutical Co. Ltd., Mitsubishi Tanabe Pharma Co., Otsuka Pharmaceutical Co. Ltd., Pfizer Japan Inc., Teijin Pharma Ltd., Grant/research support from: Chugai Pharmaceutical Co., Ltd., Mitsubishi Tanabe Pharma Co., Pfizer Japan Inc., Hiroaki Matsuno Speakers bureau: Chugai Pharmaceutical Co., Ltd., Daiichi Sankyo Co., Ltd., Eli Lilly Japan K.K., Consultant of: Mochida Pharmaceutical Co., Ltd., Grant/research support from: Astellas Pharma Inc., Eli Lilly Japan K.K.; Janssen Pharmaceutical K.K, Naoto Tsujimoto Shareholder of: Eli Lilly, Employee of: Eli Lilly Japan K.K., Atsushi Nishikawa Shareholder of: Eli Lilly, Employee of: Eli Lilly Japan K.K., Taeko Ishii Shareholder of: Eli Lilly, Employee of: Eli Lilly Japan K.K., Tsutomu Takeuchi Speakers bureau: AbbVie Japan GK, Ayumi Pharmaceutical Co., Bristol Myers Squibb Co., Ltd., Chugai Pharmaceutical Co, Ltd. Daiichi Sankyo Co., Ltd. Eisai Co., Ltd. Eli Lilly Japan K.K.; Gilead Sciences, Inc. Janssen Pharmaceutical K.K.; Mitsubishi-Tanabe Pharma Co.; Novartis Pharma Co.; Pfizer Japan Inc.; Sanofi K.K.; UCB Japan Co., Ltd., Consultant of: AbbVie Japan GK, Astellas Pharma, Inc.; Chugai Pharmaceutical Co, Ltd.; Eli Lilly Japan K.K.; Eisai Co., Ltd.; Gilead Sciences, Inc.; Janssen Pharmaceutical K.K.; Mitsubishi-Tanabe Pharma Corp., Pfizer Japan Inc., Grant/research support from: AbbVie Japan GK, Asahikasei Pharma Corp., Chugai Pharmaceutical Co, Ltd., DNA Chip Research Inc.; Eisai Co., Ltd., Eli Lilly Japan K.K.; Mitsubishi-Tanabe Pharma Corp., UCB Japan Co., Ltd., Masataka Kuwana Speakers bureau: AbbVie Japan GK, Astellas Pharma Inc., Asahi Kasei Pharma Co., Boehringer-Ingelheim, Chugai Pharmaceutical Co., Ltd., Eisai Co., Ltd., Janssen Pharmaceutical K.K., Medical &Biological Laboratories Co., Ltd.; Mitsubishi Tanabe Pharma Co.; Mochida Pharmaceutical Co., Ltd., Nippon Shinyaku Co., Ltd.; Ono Pharmaceutical Co., Ltd.; Pfizer Japan Inc., Consultant of: Boehringer-Ingelheim, Chugai Pharmaceutical Co., Ltd., Corbus Pharmaceuticals Holdings, Inc.; Medical &Biological Laboratories Co., Ltd.; Mochida Pharmaceutical Co., Ltd., Grant/research support from: Boehringer-Ingelheim, Chugai Pharmaceutical Co., Ltd., Eisai Co., Ltd., Medical &Biological Laboratories Co., Ltd; Mitsubishi Tanabe Pharma Co., Ono Pharmaceutical Co., Ltd., Michiaki Takagi Speakers bureau: Yes, but sponsored lectures without COI in the academic meetings, only.

Comprehensive Analysis of Bortezomib-Induced Adverse Events Using the Japanese Real-World Database

Oncology ◽  
2021 ◽  
Author(s):  
Aya Satoki ◽  
Mayako Uchida ◽  
Masaki Fujiwara ◽  
Yoshihiro Uesawa ◽  
Tadashi Shimizu
Keyword(s):  
Peripheral Neuropathy ◽  
Adverse Events ◽  
Cardiac Failure ◽  
Tumor Lysis Syndrome ◽  
Adverse Event Reporting System ◽  
Japanese Patients ◽  
Comprehensive Analysis ◽  
Drug Event ◽  
Lung Disorder ◽  
Time To Onset

Background: Bortezomib is used as first-line therapy for multiple myeloma. Observational studies based on the FDA Adverse Event Reporting System (FAERS) database analysis and systematic reviews indicate that the incidence of peripheral neuropathy and tumor lysis syndrome (TLS) tends to be higher with bortezomib than that of other drugs. In a comprehensive analysis assessing drugs that cause peripheral neuropathy in Japanese patients, the incidence of bortezomib-induced adverse events (AEs) was reportedly high. However, a comprehensive assessment of bortezomib is lacking. Objectives: The purpose of this study was to determine the frequency of bortezomib AEs in Japanese patients and to determine the incidence, time to onset, and post hoc outcomes of unique AEs using the Japanese Adverse Drug Event Report (JADER) database. Method: To investigate the association between bortezomib and AEs, we analyzed the JADER database, which contains spontaneous AE reports submitted to the Pharmaceuticals and Medical Devices Agency from April 2004 to December 2020. Criteria indicating the presence of an AE signal were met when the following requirements were fulfilled: proportional reporting ratios (PRR) ≥ 2 and χ2 ≥ 4. Time to onset and post-event outcomes were analyzed for characteristic AEs. Results: Among 26 extracted AEs, 13 presented AE signals. The post-exposure outcomes of 12 AEs showed fatal outcomes at rates exceeding 10%, including cardiac failure (30%), lung disorder (24%), pneumonia (18%), and TLS (10%). Furthermore, a histogram of time to onset revealed that the 12 AEs were concentrated from the beginning to approximately one month after bortezomib administration. The median onset times for cardiac failure, lung disorder, pneumonia, and TLS were 28, 13, 42, and 5 days, respectively. Conclusions: Cardiac failure, lung disorder, pneumonia, and TLS had a higher rate of fatal clinical outcomes after onset than other AEs. These AEs exhibited a greater onset tendency in the early post-dose period. This study suggests that there is a need to monitor signs of cardiac failure, lung disorder, pneumonia, and TLS, potentially resulting in serious outcomes.

scholarly journals Impact of Adiponectin and Leptin on Long-Term Adverse Events in Japanese Patients With Acute Myocardial Infarction

2013 ◽  
Vol 77 (11) ◽  
pp. 2778-2785 ◽  
Author(s):  
Yasuhiro Morita ◽  
Kengo Maeda ◽  
Takahisa Kondo ◽  
Hideki Ishii ◽  
Kyoko Matsudaira ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Acute Myocardial Infarction ◽  
Adverse Events ◽  
Japanese Patients

scholarly journals Association of the diplotype configuration at the N-acetyltransferase 2 gene with adverse events with co-trimoxazole in Japanese patients with systemic lupus erythematosus

2007 ◽  
Vol 9 (2) ◽  
pp. R23 ◽  
Author(s):  
Makoto Soejima ◽  
Tomoko Sugiura ◽  
Yasushi Kawaguchi ◽  
Manabu Kawamoto ◽  
Yasuhiro Katsumata ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Adverse Events ◽  
Lupus Erythematosus ◽  
Japanese Patients ◽  
Systemic Lupus

Phase 1 Study of Anti-CD22 Immunoconjugate Inotuzumab Ozogamicin (CMC-544) Plus Rituximab In Japanese Patients with Relapsed/Refractory B-Cell Non-Hodgkin Lymphoma

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 2872-2872 ◽  
Author(s):  
Kiyohiko Hatake ◽  
Michinori Ogura ◽  
Kiyoshi Ando ◽  
Kota Tokushige ◽  
Chiho Ono ◽  
...  
Keyword(s):  
Adverse Events ◽  
B Cell ◽  
Malt Lymphoma ◽  
Cell Lymphoma ◽  
Single Agent ◽  
Study Drug ◽  
B Cell Lymphoma ◽  
Japanese Patients ◽  
Clinical Activity ◽  
Inotuzumab Ozogamicin

Abstract Abstract 2872 Background: Inotuzumab ozogamicin (CMC-544) is a humanized anti-CD22 antibody conjugated to calicheamicin, a potent cytotoxic agent. Inotuzumab ozogamicin targets CD22, which is expressed in the majority of B-cell non-Hodgkin lymphomas (NHL). The maximum tolerated dose of inotuzumab ozogamicin administered as a single agent was previously determined to be 1.8 mg/m2 administered intravenously every 28 days, and clinical activity was shown in both non-Japanese and Japanese patients with relapsed or refractory B-cell NHL. Safety and efficacy data in non-Japanese patients with relapsed or refractory B-cell NHL treated with inotuzumab ozogamicin given in combination with rituximab was previously reported. Objectives: To assess safety, pharmacokinetics, and preliminary efficacy of inotuzumab ozogamicin in combination with rituximab in Japanese patients with relapsed or refractory B-cell NHL. Methods: Patients were eligible if they had both CD20 and CD22-positive B-cell NHL, which had not responded to or progressed after 1 or 2 therapies. At least 1 prior regimen had to contain rituximab, and patients could not have progressed under treatment or within 6 months of start of rituximab-containing therapy. Patients received 375 mg/m2 of rituximab on Day 1 followed by 1.8 mg/m2 of inotuzumab ozogamicin on Day 2 of each 28-day cycle for up to 8 cycles, provided that there was no disease progression or intolerable toxicity. Adverse events (AEs) were reported according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), version 3.0 in patients who received at least 1 dose of the study drug. Objective response rate (ORR) was evaluated according to the International Response Criteria for NHL. Results: Ten patients were enrolled and treated with 1.8 mg/m2 of inotuzumab ozogamicin in combination with rituximab for a median of 4 cycles. Median age was 60.5 (range 46 – 74), 50% were male, and 50% each had 1 and 2 prior chemotherapy regimens. Six patients were diagnosed as having follicular lymphoma (FL), 2 patients as mantle cell lymphoma (MCL), 1 patient each as diffuse large B-cell lymphoma (DLBCL) and mucosa-associated lymphoid tissue (MALT) lymphoma. Grade 3 or 4 treatment-emergent AEs reported in >20% of the patients were thrombocytopenia (70%), neutropenia (50%), leukopenia (30%), and lymphopenia (30%). AEs resulting in treatment discontinuation were neutropenia (30%) and hyperbilirubinemia (20%). No serious AEs were observed. An ORR of 80% (95% CI, 44 – 98%) was observed in the 10 patients treated. Five out of 6 patients with FL and 1 patient with MALT lymphoma achieved a complete response (CR). One out of 2 patients with MCL achieved unconfirmed CR (CRu), and 1 patient with FL attained partial response (PR). Progression-free survival (PFS) rate at 52 weeks was estimated to be 89% (95% CI, 43 – 98). ORR was 88% (95% CI, 47 – 100%) in the 8 patients that received at least 2 doses of the study drug and had at least 1 post-baseline tumor assessment (5 FL, 2 MCL, and 1 MALT lymphoma). Results of the pharmacokinetics assessment will be presented at the meeting. Conclusion: The combination of inotuzumab ozogamicin plus rituximab has a safety profile similar to that previously reported for inotuzumab ozogamicin as a single agent, with hematologic AEs being the most frequent toxicities. The preliminary but encouraging evidence of clinical activity in Japanese patients with relapsed or refractory B-cell NHL warrants continued clinical development of this combination. Disclosures: Tokushige: Pfizer Japan Inc.: Employment. Ono:Pfizer Japan Inc.: Employment. Vandendries:Pfizer Inc.: Employment, Equity Ownership.

A Clinical Pharmacology and Exploratory Study of Azacitidine Administered Subcutaneously or Intravenously In Japanese Patients with Myelodysplastic Syndrome

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 4964-4964
Author(s):  
Yukio Kobayashi ◽  
Michinori Ogura ◽  
Kiyoshi Ando ◽  
Kensei Tobinai ◽  
Toshiki Uchida ◽  
...  
Keyword(s):  
Adverse Events ◽  
Phase I ◽  
Median Time ◽  
Research Funding ◽  
Treatment Protocol ◽  
Japanese Patients ◽  
Hematologic Response ◽  
Transfusion Requirements ◽  
Grade 3 ◽  
To Receive

Abstract Abstract 4964 [Background and Purpose]: Azacitidine is a pyrimidine nucleoside analog of cytidine with hypomethylating and cytotoxic activity. Although azacitidine is currently approved for subcutaneous (SC) injection and intravenous(IV) administration for the treatment of myelodysplastic syndromes (MDS) in the US, there are limited data available on the treatment effects of IV versus SC administration. To compare the safety, pharmacokinetics (PK), and efficacy of IV with SC administration, a phase I/II study of azacitidine in Japanese patients with MDS was conducted. [Patients and Method]: Patients with RA, RA with ringed sideroblasts (RARS), RAEB, or RAEB-t defined by the French-American-British (FAB) classification were enrolled. RA and RARS must fulfill the additional criteria of significant marrow dysfunction (defined by cytopenias and/or transfusion requirements). Eligible patients were at least 20 years of age but younger than 80 and had a ECOG PS between 0 and 2. The patients were alternately assigned to receive azacitidine SC or IV (10-minutes) at 75 mg/m2/day for 7 days every 4 weeks for a minimum of 4 cycles. Patients who achieved a complete response (CR) received additional 3 cycles of azacitidine and were followed up without treatment. Subjects with a partial response (PR) or hematologic improvement (HI) received azacitidine until disease progression with a maximum of 18 cycles. Ten patients received azacitidine by both SC and IV administration on the different cycle and PK parameters were compared on day 1 of each cycle. The primary endpoints of this study were the safety, PK and HI according to the International Working Group (IWG 2006) criteria for MDS, respectively. [Results]: A total of 54 patients (10 in phase I portion and 44 in phase II portion) were enrolled between October 2007 and November 2008. Of these, 53 patients received at least one dose of azacitidine; 17 patients (32 %) were female; the median age was 65 years (range 35–77 years). FAB MDS subtypes were: RA (16/53, 30%); RARS (3/53, 6%); RAEB (20/53, 38%); RAEB-t (14/53, 26%). IPSS risk groups were: Low (0%); Int-1(23/53, 43%); Int-2(15/53, 28%); High(15/53, 28%). IPSS cytogenetic groups were: good (24/53, 45%); intermediate (13/53, 25%); poor (16/53, 30%). Fifty-one patients have completed the treatment protocol to date. The median number of treatment cycles was 7(range 1 – 18). Seven patients have completed 18 cycles of treatment. Two patients are continuing to receive treatment in their cycles 16 and 17. HI was observed in 53% (26/49) of patients. Median time to HI was 55 days (range 20–217). Of the 27 patients who were RBC transfusion dependent at baseline, 15 (56%) became transfusion independent. Hematologic response (CR, PR, or marrow CR) was achieved in 29% (15/51) of patients. Median time to hematologic response was 113 days (range 49–247). HI rate in SC and IV administration was 50 % (12/24) and 56 % (14/25), respectively. Hematologic response rate in SC and IV administration was 29% (7/24) and 30% (8/27), respectively. There were no significant differences between SC and IV administration of azacitidine for HI and hematologic response. The Cmax following IV administration was approximately 4-fold of that obtained following SC administration; however, the AUC(0-∞) following SC administration was 92.3 ± 15.8% compared to that of IV, indicating good bioavailability following SC administration. Overall, the PK profile was similar to that of the previously reported study. The most common grade 3 or 4 adverse events included neutropenia 80% (41/51), leukopenia 76% (39/51), hemoglobin decreased 71% (36/51) and thrombocytopenia 65% (33/51). Grade 3 or 4 non-hematologic adverse events which were observed more than 10% included pneumonia 12% (6/51) and hypophosphatemia 16%(8/51). There was no death during the study that occurred within 29 days of last dose of azacitidine. The safety profile did not differ significantly different between SC and IV administration with the exception of injection site reactions observed with SC administration, only. [Conclusions]: Azacitidine is generally well tolerated and demonstrated a beneficial effect in Japanese patients with MDS. The higher Cmax of IV dose was not translated into clinical outcomes; no difference was shown in both efficacy and safety profiles between SC and IV administration. Both IV and SC azacitidine are promising therapeutic options for Japanese patients with MDS. Disclosures: Kobayashi: Nippon Shinyaku Co., Ltd.: Research Funding. Ogura: Nippon Shinyaku Co., Ltd: Research Funding. Ando: Nippon Shinyaku Co., Ltd.: Research Funding. Tobinai: Nippon Shinyaku Co., Ltd.: Research Funding. Uchida: Nippon Shinyaku Co., Ltd.: Research Funding. Ogawa: Nippon Shinyaku Co., Ltd.: Research Funding. Ishikawa: Nippon Shinyaku Co., Ltd.: Research Funding. Ohashi: Nippon Shinyaku Co., Ltd.: Research Funding. Hata: Nippon Shinyaku Co., Ltd.: Research Funding. Usui: Nippon Shinyaku Co., Ltd.: Research Funding. Taniwaki: Nippon Shinyaku Co., Ltd.: Research Funding. Ohnishi: Nippon Shinyaku Co., Ltd.: Research Funding. Akiyama: Nippon Shinyaku Co., Ltd.: Research Funding. Ozawa: Nippon Shinyaku Co., Ltd.: Research Funding. Ohyashiki: Nippon Shinyaku Co., Ltd.: Research Funding. Okamoto: Nippon Shinyaku Co., Ltd.: Research Funding. Tomita: Nippon Shinyaku Co., Ltd.: Research Funding. Nakao: Nippon Shinyaku Co., Ltd.: Research Funding. Hotta: Nippon Shinyaku Co., Ltd.: Research Funding.

Phase 1 study of atrasentan (ABT627), novel endothelin receptor-A antagonist, in Japanese patients with hormone refractory prostate cancer

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 14602-14602
Author(s):  
Y. Fujisaka ◽  
Y. Fujiwara ◽  
K. Yamada ◽  
T. Shimizu ◽  
A. Horiike ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Adverse Events ◽  
Half Life ◽  
Phase 1 ◽  
Plasma Concentrations ◽  
Study Drug ◽  
Japanese Patients ◽  
Maximum Plasma ◽  
Hormone Refractory Prostate Cancer ◽  
Hormone Refractory

14602 Background: Endothelin (ET)-1 and its primary receptor, the ETA receptor, contribute to tumor cell growth, survival, angiogenesis and invasion. Atrasentan is a highly potent, selective ETA receptor antagonist. This study assessed safety and pharmacokinetics (PK) in Japanese patients with hormone refractory prostate cancer. Methods: This open-label, single-center Phase I trial evaluated the safety and PK of escalating oral atrasentan doses (2.5, 10 or 20 mg) given daily on day 1 and day 4 through 27 (except day 2 and 3). Dose-limiting toxicity (DLT) was defined as Grade 3 or greater adverse events related to study drug. Results: Eighteen patients, aged 54–74 (median; 66) were treated in cohorts of 6 patients each. The compliance of all patients was 100%. The most common toxicities were rhinitis, peripheral edema, headache, hypotension and anemia, all of which were well tolerated. These events were consistent with the anticipated vasodilatory effects or with a hemodilution effect of the study drug. DLTs were not observed. Atrasentan was rapidly absorbed following oral administration of 2.5 to 20 mg, maximum plasma concentrations averaged from 0.4 to 0.8 hours. After peaking, plasma concentrations declined bi-exponentially with a terminal half-life of approximately 25 hours. In the 10 mg dosing group, the steady-state maximum plasma concentration (Cmax) and the area under the curve (AUC0–24h) averaged 135.5 ng/mL and 533 ng h/mL, respectively. The Cmax and AUC values generally increased linearly with increasing dose after single- and multiple-dose administration. Compared to baseline, PSA decreased 50% or more in 1 patient (20 mg) and increased 25% or more in 10 patients (2.5 mg;2, 10 mg;5, 20 mg;3). The PSA of the remaining 7 patients (2.5 mg;4, 10 mg;1, 20 mg;2) ranged from < 25% increase to < 50% decrease. Fourteen patients continued on study drug in an extension study. Conclusions: Atrasentan is well tolerated, with no dose-limiting adverse events observed up to 20 mg in Japanese patients. The main adverse events are consistent with the vasodilatory effect of the drug. PK are linear and dose-proportional; the half-life is appropriate for once-daily dosing. No significant financial relationships to disclose.

A phase I/II study of biweekly XELIRI plus bevacizumab for patients with metastatic colorectal cancer as second-line chemotherapy (BIXER study): Reports of phase I part and interim analysis of phase II part.

2012 ◽  
Vol 30 (4_suppl) ◽  
pp. 643-643
Author(s):  
Mitsukuni Suenaga ◽  
Satoshi Matsusaka ◽  
Eiji Shinozaki ◽  
Nobuyuki Mizunuma ◽  
Kiyohiko Hatake ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Adverse Events ◽  
Phase I ◽  
Metastatic Colorectal Cancer ◽  
Phase Ii ◽  
Interim Analysis ◽  
Japanese Patients ◽  
Recommended Dose ◽  
Grade 3 ◽  
Dose Limiting Toxicity

643 Background: Capecitabine is an oral fluoropyrimidine prodrug, which is converted to fluorouracil (5-FU) predominantly in the tumor cells. In Japan, capecitabine is mainly used in combination with oxaliplatin (XELOX) in treatment for metastatic colorectal cancer (mCRC) since its approval in 2009. The results of capecitabine plus Irinotecan (CPT) (XELIRI) with or without bevacizumab (BV) in EU or US patients were previously reported, but not in Japanese. Thus, we conducted this study to assess the safety and efficacy of XELIRI plus BV in Japanese patients with mCRC. Methods: Patients with prior chemotherapy including oxaliplatin and BV for mCRC, wild or hetero type of UGT1A1 *6*28 were eligible for this study. This was a phase I study composed of two steps, and dose limiting toxicity (DLT) was assessed during the first treatment cycle. Treatment comprised capecitabine 1,000 mg/m2 twice daily from the evening of day 1 to the morning of day 8, intravenous CPT 180 mg/m2 on day 1, and BV 5mg/kg on day 1 every two weeks. To evaluate the initial safety, 3-6 patients received XELIRI+BV (CPT 150mg/m2) in step 1, and 6 patients received XELIRI+BV (CPT 180mg/m2) in step 2. If DLT occurred in 1 patient in step1, 3 patients would be newly added to step 1, and if in none of 3 or 1-2 of 6 patients, the step 2 would be started. If DLT occurred in less than or equal to 2 of 6 patients in step 2, phase II study would be proceeded, and if In more than 2 of 6 patients, phase II would be conducted at the recommended dose of step 1. Results: In step 1 and 2 of phase I, initial safety of 9 patients was confirmed without occurrence of DLT. Adverse events observed in step 1 and 2 were: neutropenia in 2 and 1; anorexia in 1 and 1; diarrhea in 1 and 1; stomatitis in 1 and 1; alanine or aspartate aminotransferase increased in 1 and 3, respectively. There was no grade 3 or greater adverse events. Conclusions: In mCRC patients with wild or hetero of UGT1A1*6*28 genotype, safety of biweekly XELIRI+BV was confirmed and recommended dose of CPT-11 was determined as 180mg/m2. Interim analysis of safety of phase II part will be reported at the meeting.

Management tips for the low incidence, of adverse events and well efficacy of regorafenib for metastatic colorectal cancer in Juntendo University Medical Hospital.

2015 ◽  
Vol 33 (3_suppl) ◽  
pp. 778-778 ◽  
Author(s):  
Yoshie Higashihara ◽  
Nobuko Serizawa ◽  
Junko Kato ◽  
Tomohiro Kodani ◽  
Taro Osada ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Adverse Events ◽  
Metastatic Colorectal Cancer ◽  
Kinase Inhibitor ◽  
Japanese Patients ◽  
Similar Efficacy ◽  
Treatment Discontinuation ◽  
Common Grade ◽  
Low Incidence ◽  
Grade 3

778 Background: Regorafenib is an oral multi-kinase inhibitor that has demonstrated significant overall survival for metastatic colorectal cancer in CORRECT study. In the Japanese subset of CORRECT study, adverse events (AEs) such as hand-foot skin reaction (HFSR), anorexia, and liver dysfunction occurred at high frequency. Therefore, those AEs were one of the causes for treatment discontinuation. Methods: We retrospectively analyzed the safety and efficacy in 14 patients who received regorafenib monotherapy in our hospital between June 2013 and August 2014. Results: Among the 14 patients, median age was 64.5 years old (range 53-76). Median follows up time was 209 days (range 72-340), median PFS was 64 days (range 19-272), and median TTF was 66.5 days (range 18-280). There was no patient who had complete or partial response. The disease control rate was 36%. Nine patients initiated with 160 mg of regorafenib once daily, 4 patients with 120 mg, and one patient with 80 mg. The most common grade 3 or more AEs were HFSR, AST and ALT elevations and hypertension (2 patients, 14.2%, respectively). The frequency of HFSR was lower in our cohort the Japanese patients of CORRECT study. Treatment discontinuation due to drug related AEs occurred to 5 patients (35.7%). Dose reduction and interruption of regorafenib were required in 10 patients (71.4%) and 8 patients (57.1%), respectively. For prevention of HFSR, more than 90% of the patients were received proactive treatment including heparinoid and strong steroid from the start of the therapy. We carefully monitored their toxicities every week during the first cycle, and chose interruption if patients were had more grade 2 AEs. It is very important, we think to give the patients instructions on possible AEs and how to manage them using an illustrated book. Conclusions: Our cohort had lower HFSR in frequency than and similar efficacy to the Japanese subpopulation in CORRECT study. Enough explanation and instruction to patients might be important to decrease an incidence of AEs and treatment discontinuation due to drug- related AEs. We will increase the number of cases and examine in future.

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