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by
Y Komatsu |
Total Records (
4 ) for
Y Komatsu |
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A Yasoda
,
H Kitamura
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T Fujii
,
E Kondo
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N Murao
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M Miura
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N Kanamoto
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Y Komatsu
,
H Arai
and
K. Nakao
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Skeletal dysplasias are a group of genetic disorders characterized by severe impairment of bone growth. Various forms of them add to produce a significant morbidity and mortality, yet no efficient drug therapy has been developed to date. We previously demonstrated that C-type natriuretic peptide (CNP), a member of the natriuretic peptide family, is a potent stimulator of endochondral bone growth. Furthermore, we exhibited that targeted overexpression of a CNP transgene in the growth plate rescued the impaired bone growth observed in a mouse model of achondroplasia (Ach), the most frequent form of human skeletal dysplasias, leading us to propose that CNP may prove to be an effective treatment for this disorder. In the present study, to elucidate whether or not the systemic administration of CNP is a novel drug therapy for skeletal dysplasias, we have investigated the effects of plasma CNP on impaired bone growth in Ach mice that specifically overexpress CNP in the liver under the control of human serum amyloid P component promoter or in those treated with a continuous CNP infusion system. Our results demonstrated that increased plasma CNP from the liver or by iv administration of synthetic CNP-22 rescued the impaired bone growth phenotype of Ach mice without significant adverse effects. These results indicate that treatment with systemic CNP is a potential therapeutic strategy for skeletal dysplasias, including Ach, in humans. |
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K Shitara
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T Yokota
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D Takahari
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T Shibata
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T Ura
,
Y Komatsu
,
S Yuki
,
M Yoshida
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H Takiuchi
,
S Utsunomiya
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Y Yatabe
and
K. Muro
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Standard weekly cetuximab and irinotecan is an effective regimen in heavily pre-treated patients with metastatic colorectal cancer. The aim of this study is to prospectively evaluate the efficacy of combination chemotherapy with biweekly cetuximab and irinotecan in patients with pre-treated metastatic colorectal cancer harboring wild-type KRAS. A total of 30 patients will be enrolled at four medical institutions. The primary endpoint is response rate. The secondary endpoints include adverse events, progression-free survival and overall survival. The pharmacokinetics of cetuximab will also be evaluated in five patients. |
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T Doi
,
N Boku
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K Kato
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Y Komatsu
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K Yamaguchi
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K Muro
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Y Hamamoto
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A Sato
,
W Koizumi
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N Mizunuma
and
H. Takiuchi
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Objective
The addition of bevacizumab to fluoropyrimidine-based combination chemotherapy as first-line therapy for metastatic colorectal cancer results in clinically significant improvements in patient outcome. However, clinical trials have been conducted primarily in Caucasian patients with only a small proportion of Asian patients. This Phase I/II study was designed to evaluate the efficacy and safety of XELOX (capecitabine plus oxaliplatin) plus bevacizumab in Japanese patients with metastatic colorectal cancer.
Methods
Patients with previously untreated, measurable metastatic colorectal cancer received bevacizumab 7.5 mg/kg and oxaliplatin 130 mg/m2 on day 1, plus capecitabine 1000 mg/m2 twice daily on days 1–14, every 3 weeks. A three-step design evaluated in: step 1, initial safety of XELOX in six patients; step 2, initial safety of XELOX plus bevacizumab in six patients; and step 3, efficacy and safety in a further 48 patients. The primary study endpoints were safety and response rate.
Results
No dose-limiting toxicity occurred during Steps 1 and 2. Fifty-eight patients were enrolled in Steps 2 and 3 and received XELOX plus bevacizumab. In the 57 patients assessed for response, the overall response rate was 72% (95% confidence interval, 58.5–83.0). Median progression-free survival was 11.0 months (95% confidence interval, 9.6–12.5) and median overall survival was 27.4 months (95% confidence interval, 22.0–not calculated). Eight patients (14%) underwent surgery with curative intent. The most common grade 3/4 adverse events were neurosensory toxicity (17%) and neutropenia (16%).
Conclusions
XELOX plus bevacizumab is effective and has a manageable tolerability profile when given to Japanese patients with metastatic colorectal cancer.
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