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Biomedical subjects

Yasuo Ohashi

Publications and source records attributed to Yasuo Ohashi.

At least 55 records · Page 3Linked to original sources
PubMed2005

[Cancer screening].

The purpose of cancer screening is to widen the difference between morbidity and mortality of the target cancer. Since 1983 cancer screening has been supported by the Japanese government. Initially it covered gastric and cervical cancer with lung, breast and endometrial cancers supported from 1987 and colorectal cancer in 1992. Since 1998 support for cancer screening has been transferred to local government. It is generally accepted that the uptake of screening services is too low. Estimates for Japan suggest that at best 30% of the eligible population accept the services. In other parts of the world screening is more widely accepted, for example, 67% for breast cancer and 79% for cervical screening in the USA. Barriers within Japan for increasing screening are complex and include, legal, ethical, financial, technical infrastructure, data related matters and the level of understanding and education of the general public. In 2000 the MHLW conducted an evaluation of cancer screening in terms of usefulness and effectiveness. It concluded that fair or better evidence for reduction in mortality existed for cervical cancer (cytology), breast cancer (mammography with clinical examination for women aged > or = 50 years), colorectal cancer (faecal occult blood test), gastric cancer, lung cancer and liver cancer. As a step towards improving screening services and their uptake by the general public a new Research Centre for Cancer Prevention and Screening was established at the National Cancer Centre in October 2003. This and other initiatives will build on the progress of the past 20 years but it is generally agreed that there is still have a long way to go.

Adult↗
PubMed2005

[A clinical study of YM 294 (rhlL-11) in patients with gynecologic cancer].

YM 294 was administered for chemotherapy-induced thrombocytopenia in patients with gynecologic cancer at a dose of 50 microg/kg in order to examine the efficacy and safety by a randomized trial, using the non-treatment observation group as a control. Increase in the nadir platelet counts as well as shortening of the days to return the platelet number to>100,000/ microl were significantly higher in the 50 microg/kg groups, in comparison with the non-treatment observation group. The major adverse drug reactions observed in the 50 microg/kg groups were edema, erythema of injection site, and fever. All of these adverse reactions were either mild or moderate (not serious), and they resolved. Abnormal changes in laboratory value for which a casual relationship with the study drug could not be excluded were reversible and manageable. The efficacy and safety of 50 microg/kg groups for chemotherapy-induced thrombocytopenia in patients with gynecological cancer was confirmed by the results of this study.

Adult↗
PubMed2005

A multicenter randomized study comparing 5-fluorouracil continuous infusion (ci) plus 1-hexylcarbamoyl-5-fluorouracil and 5-FU ci alone in colorectal cancer.

To verify the effectiveness of oral 1-hexylcarbamoyl-5-fluorouracil (HCFU) in improving the surgical cure rate in advanced colorectal cancer, a multicenter randomized comparative study was conducted. A total of 429 patients who had had curative resection for stage II and III colorectal cancer were randomly assigned to a study group receiving a 14-day course of 5-FU continuous infusion (320 mg/m2/day) followed by oral HCFU for a year (300 mg/day), or to the control group receiving a 14-day course of 5-FU continuous infusion alone. In terms of background factors, no significant differences were found between the 214 patients in the study group and the 215 in the control group. Adverse reactions during the treatment were more frequently seen in the study group. But with few exceptions, the toxicities were mild and the compliance was acceptable. The 5-year overall survival rate of the study group was similar to that of the control group. The 5-year disease-free survival rate of the study group was better than that of the control group in the patients with colon cancer (hazard ratio=1.87; 95% confidence interval 1.03-3.38; p=0.037). However, this benefit was not seen in the patients with rectal cancer. A significant improvement in the disease-free survival rate was demonstrated through the addition of HCFU to 5-FU continuous infusion for the patients with colon cancer. The usefulness of oral fluoropyrimidine as an adjuvant for curative surgery for colon cancer was further warranted.

Adult↗
PubMed2005

[A Monte-Carlo study for propensity score methods].

OBJECTIVE: To evaluate the statistical property of the estimators on exposure effect and value of propensity score methods in practical use. METHODS: Simulation data, propensity score methods (PSM) were conducted to assess bias and efficiency, under both with/without model misspecification conditions. RESULTS: Under model misspecification conditions, propensity score methods had better robustness than model based methods. CONCLUSION: For large and complicated data, propensity score methods had more flexibility in practical use than model based methods.

Algorithms↗
PubMed2005

[Cancer prevention].

The 12 th Oncology Forum discussed the progress and future strategy of cancer prevention in Japan. The National Cancer Center has established a research center for screening focusing on the most common six cancer, stomach, lung, liver, colon, breast and uterus cancer. The program so far had a cumulative detection rate of 3.3%, which is high,and may reflect the selection of subjects. Screening and chemoprevention is also being investigated in prostate cancer, but the issues centre on how to make this widely available. High risk subjects can also be identified for breast cancer. Obesity and family history are especially important. In colorectal cancer studies are evaluating different diets, but general application is not yet possible and the infrastructure to implement any general screening and prevention does not exist. Development of pharmaceutical treatments for prevention is difficult because of the need for very safe treatments, and also because of the length of time needed to carry out studies. Overall, cancer prevention is still in evolution. New approaches are needed, and new infrastructure will be needed at a government level to implement this.

Breast Neoplasms↗
PubMed2005

[Assessment of goserelin treatment in adjuvant therapy for premenopausal patients with breast cancer in Japan-zoladex breast cancer study group trial-B].

OBJECTIVE: Goserelin (GOS) therapy in an adjuvant setting for estrogen receptor(ER)-positive premenopausal patients with breast cancer was assessed in a randomised comparative study. METHODS: ER positive premenopausal patients with n + or n 0 and T > or = 3 cm received tamoxifen (TAM) 20 mg/day, GOS 3.6 mg/4 weeks or GOS + TAM for 2 years, and the clinical efficacy and safety of these regimens were assessed. RESULTS: In the data analysis of total 207 patients, hazard ratios of disease free survival (DFS) and overall survival (OS) in the GOS group compared to the TAM group were 0.87 and 2.10,respectively. The incidence of adverse drug reactions was similar (42-55%) in all three groups. Since the number of patients in this study did not reach the target number, the efficacy could not be assessed from a statistical aspect. Therefore,meta-analysis with similar foreign studies(ZIPP) was implemented. The results of meta-analysis showed that the hazard ratios of DFS and OS in the GOS group compared to the non-GOS group were 0.83 and 0.85, respectively. CONCLUSION: Although the analysis of 207 patients did not show any statistically significant difference between each of the treatment groups, the results of meta-analysis showed a significant prolongation of DFS in the GOS group. Also high tolerability of GOS was suggested. From these results, GOS was considered highly useful in adjuvant therapy for ER-positive premenopausal patients with breast cancer.

Adult↗
PubMed2004

Adjusting for differential proportions of second-line treatment in cancer clinical trials. Part I: structural nested models and marginal structural models to test and estimate treatment arm effects.

In randomized trials, post-randomization variables such as compliance, prescription of alternative treatments and so on are usually ignored to compare treatment arms. Intent-to-treat (ITT) analysis is a standard approach but it does not adjust for those variables. However, we may need to evaluate treatment arm effects that have the desired causal interpretation. Previously proposed methods such as time-dependent Cox model may not properly adjust for post-randomization variables and may produce biased results. Alternatively, we propose to use two causal models, structural nested models and marginal structural models. The two models appropriately adjust for such variables. We apply these models to adjust for differential proportions of post-randomization second-line treatment in cancer clinical trials. With sufficient care to several assumptions, these methods, especially structural nested failure time models with randomized analyses, are useful to take the influence of second-line treatment into account and to test and estimate the direct treatment arm effect.

Humans↗
PubMed2004

Adjusting for differential proportions of second-line treatment in cancer clinical trials. Part II: an application in a clinical trial of unresectable non-small-cell lung cancer.

The CPT-11 trial was conducted to confirm the superiority of CDDP+CPT-11 (CPT-P) arm to CDDP+VDS (VDS-P) arm with regard to survival for patients with previously untreated advanced (stage IIIB/IV) non-small-cell lung cancer. However, the CPT-P arm did not show the survival benefit for patients with stage IIIB. The proportion of patients with stage IIIB treated by active radiation given as second-line treatment (second-line radiotherapy) after initial (first-line) treatment was 45 per cent in the CPT-P arm while 61 per cent in the VDS-P arm. This showed that not proving survival advantage in the CPT-P arm might be due to the benefits of second-line radiotherapy. We apply two causal models appeared in the companion paper to test and estimate the survival differences that would have been observed if all the patients had been received the same second-line radiotherapy. Based on several assumptions, we inferred that the CPT-P arm still would not have showed survival advantage if all the patients had been given identical second-line radiotherapy.

Adult↗
PubMed2004

Efficacy of oral adjuvant therapy after resection of colorectal cancer: 5-year results from three randomized trials.

PURPOSE: Adjuvant therapy of colorectal cancer with oral fluorinated pyrimidines is attractive because of its ease of administration and good tolerability. The purpose of this meta-analysis is to assess the survival and disease-free survival benefits of treating patients after surgical resection of a primary colorectal tumor with oral fluoropyrimidines for 1 year. PATIENTS AND METHODS: This meta-analysis was performed on individual data from three randomized trials conducted by the Japanese Foundation for Multidisciplinary Treatment for Cancer involving a total of 5,233 patients with stages I to III colorectal cancer. RESULTS: The overall hazard ratio in favor of oral therapy was 0.89 for survival (95% CI, 0.80 to 0.99; P =.04), and 0.85 for disease-free survival (95% CI, 0.77 to 0.93; P <.001). Thus oral therapy reduced the risk of death by 11% and the risk of recurrence or death by 15%. There was no significant heterogeneity between trials, nor did the benefit of oral therapy depend on tumor stage (I, II, or III), tumor site (rectum or colon), patient age, or patient sex. CONCLUSION: Oral fluoropyrimidines improve disease-free survival and survival of patients after resection of early-stage colorectal cancer. These observations support the use of these agents alone after resection of early-stage disease, as well as further testing of oral agents in combination with new drugs that have recently shown antitumor activity in advanced colorectal cancer.

Administration, Oral↗
PubMed2004

Phase III randomized trial of docetaxel plus cisplatin versus vindesine plus cisplatin in patients with stage IV non-small-cell lung cancer: the Japanese Taxotere Lung Cancer Study Group.

PURPOSE: Few randomized trials have demonstrated survival benefit of combination chemotherapy involving new agents plus cisplatin compared with classic combination chemotherapy in advanced non-small-cell lung cancer (NSCLC). The primary aim of this study was to test whether docetaxel plus cisplatin (DC) improves survival compared with vindesine plus cisplatin (VdsC) in patients with previously untreated stage IV NSCLC. PATIENTS AND METHODS: Eligible, stage IV, chemotherapy-naive patients (n = 311) were randomly assigned to receive docetaxel 60 mg/m(2) intravenously on day 1 plus cisplatin 80 mg/m(2) intravenously on day 1 of a 3- or 4-week cycle, or vindesine 3 mg/m(2) intravenously on days 1, 8, and 15 plus cisplatin 80 mg/m(2) intravenously on day 1 of a 4-week cycle. Cross-over administration of docetaxel and vindesine was prohibited for both treatment groups. RESULTS: Overall, 302 patients were eligible for evaluation. The DC arm demonstrated significant improvements compared with the VdsC arm in overall response rates (37% v 21%, respectively; P <.01) and median survival times (11.3 v 9.6 months, respectively; P =.014). Two-year survival rates were 24% for the DC arm compared with 12% for the VdsC arm. The physical domain of the Quality of Life for Cancer Patients Treated with Anticancer Drugs measure was significantly better in the DC arm than in the VdsC arm (P =.020). Toxicity was predominantly hematologic and was more severe in the VdsC arm. CONCLUSION: As first-line treatment for stage IV NSCLC, DC resulted in greater clinical benefit in terms of response rate (with marked improvements in overall and 2-year survival rates) and quality of life than did treatment with VdsC.

Adult↗
PubMed2004

Efficacy of prophylactic intravenous granisetron in postoperative emesis in adults.

PURPOSE: This randomized, double-blind, placebo-controlled trial evaluated the efficacy, safety, and optimal dose of granisetron in the prophylactic control of postoperative nausea and vomiting in patients undergoing gynecologic surgery or cholecystectomy. METHODS: Three-hundred and fifteen patients (age, 20-65 years) received intravenous granisetron (1 mg or 3 mg) or placebo immediately before the end of anesthesia. After treatment, patients were observed for 24 h, and the occurrence of nausea and vomiting was recorded and safety was assessed. The no-vomiting rate, time-to-first vomiting episode, and severity of nausea were recorded. RESULTS: The no-vomiting rates in patients receiving granisetron 1 mg and 3 mg were significantly higher than that in the placebo group (83.7%, 78.8%, and 57.9%, respectively; P = 0.0004 for 1 mg vs placebo, P = 0.001 for 3 mg). Time-to-first vomiting episode was longer in the granisetron 1-mg and 3-mg groups than in the placebo group (time-to-event analysis, Kaplan-Meier, log-rank test; 83.2%, 80.1%, and 59.1%, respectively; P = 0.0002 and P = 0.0010). The severity of nausea was also less in granisetron-treated patients (25.2%, 11.5%, and 15.4% severe nausea incidence for placebo, granisetron 1 mg, and granisetron 3 mg, respectively; P = 0.00003 and P = 0.002). Fewer rescue medications were required in the two granisetron-treated groups compared with those receiving placebo. Adverse events were similar in all groups. No differences in efficacy or safety were observed between granisetron doses. CONCLUSION: Granisetron is well-tolerated and more effective than placebo in the prophylactic control of nausea and vomiting after surgery. This study suggests that the optimum dose of granisetron is 1 mg.

Adult↗
PubMed2004

A comparison of incidences of vertebral fracture in Japanese patients with involutional osteoporosis treated with risedronate and etidronate: a randomized, double-masked trial.

To demonstrate the clinical benefit of risedronate at 2.5 mg daily in the treatment of involutional osteoporosis, the effect of risedronate on incidence of vertebral fracture was compared with that of etidronate. A total of 547 patients with one to four vertebral fractures were randomized to receive either treatment with 2.5 mg/day of risedronate or intermittent treatment (treatment of 2 weeks and off period of 10 weeks) with 200 mg/day of etidronate for 96 weeks in a double-masked fashion. All patients received 200 mg calcium supplement daily. Lateral and anteroposterior thoracic and lumbar spine radiographs were obtained at baseline and at 24, 48, 72, and 96 weeks. Cumulative incidence rates of patients who had at least one new or worsening vertebral fracture during the 96-week period were 12.3% for risedronate and 14.2% for etidronate, and it was verified that the fracture prevention effect of risedronate was not inferior to that of etidronate. The incidence rates of fracture during the initial 24-week period were 8.8% for risedronate and 6.0% for etidronate, but the cumulative incidence rate of fracture from 24 to 96 weeks was lower in the risedronate group (3.9%) as compared to the etidronate group (8.7%). Height loss was significantly less in the risedronate group (-0.28 cm) than in the etidronate group (-0.70 cm) after 96 weeks. Decreases in bone resorption markers including urinary total deoxypyridinoline and NTX were significantly greater in the risedronate group than in the etidronate group throughout the treatment period. An improvement of patient QOL was observed in both groups. No significant difference in the incidence of adverse events was observed between the two treatments. Daily oral risedronate (2.5 mg) was shown to provide an effective therapy for involutional osteoporosis in Japanese patients with good tolerability.

Aged↗
PubMed2004

Randomized controlled trial of the efficacy of adjuvant immunochemotherapy and adjuvant chemotherapy for colorectal cancer, using different combinations of the intracutaneous streptococcal preparation OK-432 and the oral pyrimidines 1-hexylcarbamoyl-5-fluorouracil and uracil/tegafur.

BACKGROUND: We investigated the efficacy and safety of adjuvant immunochemotherapy and adjuvant chemotherapy for colorectal cancer, using different combinations of the intracutaneous streptococcal preparation OK-432 and the oral pyrimidines 1-hexylcarbamoyl-5-fluorouracil (carmofur, HCFU) and uracil/tegafur (UFT). METHODS: Patients with stage II, III, or IV (Dukes' B, C) colorectal cancer were enrolled and randomly assigned to one of three groups: an immunochemotherapy group (mitomycin C [MMC] + 5-fluorouracil [5-FU] + HCFU + OK-432), a chemotherapy group (MMC + 5-FU + HCFU), and a control group (surgery alone) for those with colon cancer (study 1); and an immunochemotherapy group (MMC + 5-FU + UFT + OK-432), a chemotherapy group (MMC + 5-FU + UFT), and a control group (surgery alone) for those with rectal cancer (study 2). RESULTS: A total of 760 patients with colon cancer and 669 patients with rectal cancer were entered into this randomized clinical trial (RCT). The incidence of side-effects was in the order of: immunochemotherapy group >> chemotherapy group >> control group in both the cohort of patients with colon cancer and the cohort with rectal cancer. In particular, the frequency of leucopenia and skin disorders was significantly higher than control groups. There were no severe adverse events such as death related to the adjuvant therapy. In both the colon cancer and rectal cancer cohorts, no significant difference in the 5-year survival rate and disease-free survival rate was noted among the three groups. CONCLUSION: The results of an RCT demonstrated that the combination of MMC + 5-FU + HCFU + OK-432 for colon cancer and that of MMC + 5-FU + UFT + OK-432 for rectal cancer could not prolong the survival of patients with surgically resected colorectal cancer, but that both combinations were well tolerated as adjuvant therapy. We investigated the efficacy and safety of adjuvant immunochemotherapy and adjuvant chemotherapy for colorectal cancer, using different combinations of the intracutaneous streptococcal preparation OK-432 and the oral pyrimidines 1-hexylcarbamoyl-5-fluorouracil (carmofur, HCFU) and uracil/tegafur (UFT).

Administration, Oral↗
PubMed2004

Identification of DNA copy number changes in microdissected serous ovarian cancer tissue using a cDNA microarray platform.

We have established a method for using a cDNA array platform in combination with degenerate oligonucleotide primer polymerase chain reaction (DOP-PCR) and taramide signal amplification (TSA) to identify DNA copy number abnormalities (CNA) in cancer cell lines and cancer cells procured with laser-based microdissection. To determine the sensitivity and specificity for detecting single-copy gain and loss, receiver-operator curve analysis was performed on hybridization signal ratios generated from non-DOP and DOP amplified female and male DNA using a 10,816-element cDNA microarray. A cutoff value of 1.12 and 1.07 average signal ratio for X-chromosomal genes versus autosomal genes provided a sensitivity and specificity of 50 and 79%, respectively, for non-DOP amplified DNA and a sensitivity and specificity of 50 and 72%, respectively, for DOP amplified DNA. We used this approach to identify DNA copy number abnormalities in the ovarian cancer cell line OVCA633, which has previously been shown to have 12p amplification. Transcription profiling of OVCA633 was also performed. Two amplified and overexpressed genes located on 12p11, KRAS2 and LRMP, were identified; these were validated with quantitative real-time PCR. Subsequently, the same approach was used to identify CNAs and gene expression alterations in 11 microdissected serous ovarian adenocarcinoma cases. Validated data revealed amplification and overexpression of ERBB3 and FOS and deletion and underexpression of KRT6 and APXL in more than 50% of the tissue samples. These results show the feasibility of using the cDNA array platform to identify changes in DNA and mRNA copy number simultaneously in microdissected tumor tissues.

Adenocarcinoma↗