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Articles by T Okusaka
Total Records ( 5 ) for T Okusaka
  Y Seki , T Okusaka , M Ikeda , C Morizane and H. Ueno
 

Pancreatic acinar cell carcinoma (ACC) is a comparatively rare tumor and account for ~1% of all cases of pancreatic cancer. Clinical presentation is usually related to either local spread or metastasis. The clinical features, especially those related to the prognosis and treatment outcomes, have not yet been fully clarified. There are no established treatments for unresectable pancreatic ACC. We administered gemcitabine monotherapy to four patients with ACC; however, the results were not satisfactory. Disease control without obvious tumor shrinkage was observed in one patient. Another patient showed severe renal damage caused by gemcitabine. On the other hand, fluoropyrimidine-based chemotherapy may have some activity against this tumor, because one of the three patients who received S-1 as second-line chemotherapy showed a partial response. Prospective clinical trials are necessary to confirm the effectiveness of fluoropyrimidine for the treatment of pancreatic ACC.

  A Soeda , Y Morita Hoshi , H Makiyama , C Morizane , H Ueno , M Ikeda , T Okusaka , S Yamagata , N Takahashi , I Hyodo , Y Takaue and Y. Heike
  Objective

Chemotherapy and immunotherapy often seem to contradict each other. However, recent reports suggested that the anticancer effects in some chemotherapeutic agents were concerned with immune response. This study was designed to evaluate the immunological reaction by gemcitabine for future clinical trial of combination therapy with gemcitabine and cancer vaccines.

Methods

We evaluated several immunological parameters in patients with advanced pancreatic cancer who received a conventional dose of gemcitabine for 2 months. Twenty-eight patients with metastasis or locally advanced tumor, including 18 gemcitabine-naïve and 10 with a history of preceding gemcitabine treatment, were enrolled in this study. The patients received gemcitabine 1000 mg/m2 for 3 weeks, followed by 1 week of rest. We monitored the kinetics of lymphocytes, natural killer cells, monocytes, dendritic cells (DC), human leukocyte antigen (HLA)-multimer conjugated with CMV or WT1 peptide, and intracellular cytokine production of interferon- and interleukin-4 by flow cytometry. The T cell receptor (TCR) repertoire was also analyzed.

Results

The absolute number and percentage of CD14+ monocytes and CD11c+ (myeloid) DC increased with gemcitabine treatment (P = 0.033 and P = 0.021). The percentage of CD123+ (plasmacytoid) DC also increased (P = 0.034), whereas no significant change was observed in other immune parameters, including multimer, intracellular cytokine production and TCR repertoire.

Conclusions

Our finding that gemcitabine treatment induced the proliferation of CD14+ monocytes and CD11c+ DC could support combination therapy with gemcitabine and specific immunotherapy such as peptide vaccination against pancreatic cancers.

  S Iwasa , C Morizane , T Okusaka , H Ueno , M Ikeda , S Kondo , T Tanaka , K Nakachi , S Mitsunaga , Y Kojima , A Hagihara and N. Hiraoka
  Objective

The combination chemotherapy consisting of cisplatin and etoposide, one of the standard regimens for small cell lung cancer, has been widely used to treat extrapulmonary poorly differentiated neuroendocrine carcinomas. However, there were no prior reports limited to the hepatobiliary tract and pancreas as the primary sites.

Methods

We reviewed the cases in our database from October 1995 to January 2009 and retrospectively examined the clinical data of patients, with unresectable or recurrent poorly differentiated neuroendocrine carcinoma arising from the hepatobiliary tract and pancreas, who received combination chemotherapy with cisplatin and etoposide as the first-line treatment. The chemotherapy regimen consisted of cisplatin 80 mg/m2 given intravenously on day 1 and etoposide 100 mg/m2 intravenously on days 1–3, repeated every 3–4 weeks.

Results

Twenty-one patients were treated with the above regimen of cisplatin and etoposide combination chemotherapy. The primary tumor site was the liver in 2 patients, gallbladder in 8 patients, pancreas in 10 patients and ampulla of Vater in 1 patient. Although no complete responses were obtained, three patients had partial responses, resulting in an overall response rate of 14%. Median progression-free survival was 1.8 months, and median overall survival was 5.8 months. The major adverse events were myelosuppression and gastrointestinal toxicities, with Grade 3 or 4 neutropenia (90%), nausea (33%) and anorexia (24%).

Conclusions

Cisplatin and etoposide combination as the first-line chemotherapy for hepatobiliary or pancreatic poorly differentiated neuroendocrine carcinoma had only marginal antitumor activity and relatively severe toxicity compared with previous studies on extrapulmonary poorly differentiated neuroendocrine carcinoma treated with the same regimen.

  A Soeda , Y Morita Hoshi , M Kaida , T Wakeda , Y Yamaki , Y Kojima , H Ueno , S Kondo , C Morizane , M Ikeda , T Okusaka and Y. Heike
 

The skin toxicity of vaccine therapy at injection sites is generally limited to Grades 1–2 due to the nature of their function. We experienced two cases of severe and prolonged local adverse effects in 25 patients following a Phase I study of gemcitabine and Wilms tumor-1 peptide vaccine mixed with incomplete Freund's adjuvant for inoperable pancreatic or biliary tract cancer. These patients requested to continue the treatment after the study period; however, in the course of compassionate use, they developed unacceptable local skin reactions and terminated their vaccine treatment. One patient (human leukocyte antigen, A0201, 3 mg) developed Grade 3 ulceration at the 10th vaccination and another (human leukocyte antigen, A2402, 1 mg) developed Grade 2 indulation and fibrosis at the 16th vaccination. Skin toxicity occurred at 6.4–8.4 months and continued for several months after the final vaccination during gemcitabine treatment. In these cases, activation or induction of Wilms tumor-1-specific T lymphocytes was not apparent in the peripheral blood despite their severe local reactions. Therefore, we need to monitor patients for late-onset, severe and long-lasting skin reactions at injection sites in Wilms tumor-1 cancer vaccine therapy, particularly for combination treatment with gemcitabine.

  A Takashima , C Morizane , H Ishii , K Nakamura , H Fukuda , T Okusaka and J. Furuse
 

A randomized Phase II selection design trial comparing gemcitabine plus S-1 combination therapy with S-1 monotherapy for chemo-naïve unresectable or recurrent biliary tract cancer patients was started in Japan. The aim of this trial is to evaluate the efficacy and safety of the two regimens and to determine which is more promising as a test arm regimen to be compared with the current standard regimen, gemcitabine plus cisplatin, in a subsequent Phase III trial. Patients with unresectable or recurrent biliary tract cancer are randomized to either gemcitabine plus S-1 combination therapy arm or S-1 monotherapy arm. A total of 100 patients will be accrued for this study from 18 institutions over 1 year. The primary endpoint is the proportion of 1-year overall survival, and the secondary endpoints are progression-free survival, response rate and adverse events.

 
 
 
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