Biomedical subjects

Naoki Ishizuka

Publications and source records attributed to Naoki Ishizuka.

13 recordsLinked to original sources

PubMed2006

[Hepatic lymph node involvement in patients with synchronous multiple liver metastases of colorectal cancer].

BACKGROUND AND PURPOSE: Hepatic arterial infusion chemotherapy for unresectable liver metastases of colorectal cancer is generally indicated to patients without extra hepatic lesions. This study was performed to examine the status of hepatic lymph node metastasis as an extra hepatic lesion in patients with synchronous multiple liver metastases of colorectal cancer. PATIENTS AND METHODS: A total of 111 hepatic lymph nodes were removed from 33 patients with synchronous liver metastases of colorectal cancer during resection of the primary tumor at the D2- or D3- level. The frequency of hepatic lymph node metastases and factors predictive for hepatic lymph node metastasis were examined. RESULTS: Hepatic lymph node metastasis was detected in nine patients (27%): The sites were classified into three categories: (1) along the hepatic arteries in three, (2) in the hepato-duodenal ligament except the peri-hepatic arterial region in three, and (3) both in three. The serum level of CEA (p = 0.02), CA19-9 (p = 0.05), and the rate of lymph node metastasis of the primary lesion (p = 0.08) were higher or tended to be higher in patients with hepatic lymph node metastases than in those without. There was no significant relationship between the involvement of hepatic lymph nodes and the other clinicopathologic factors examined. CONCLUSION: We should note the frequency of hepatic lymph node metastasis in the treatment of unresectable liver metastases of colorectal cancer.

Carcinoembryonic Antigen↗

PubMed2005

Randomized pharmacokinetic and pharmacodynamic study of docetaxel: dosing based on body-surface area compared with individualized dosing based on cytochrome P450 activity estimated using a urinary metabolite of exogenous cortisol.

PURPOSE: Docetaxel is metabolized by cytochrome P450 (CYP3A4) enzyme, and the area under the concentration-time curve (AUC) is correlated with neutropenia. We developed a novel method for estimating the interpatient variability of CYP3A4 activity by the urinary metabolite of exogenous cortisol (6-beta-hydroxycortisol [6-beta-OHF]). This study was designed to assess whether the application of our method to individualized dosing could decrease pharmacokinetic (PK) and pharmacodynamic (PD) variability compared with body-surface area (BSA) -based dosing. PATIENTS AND METHODS: Fifty-nine patients with advanced non-small-cell lung cancer were randomly assigned to either the BSA-based arm or individualized arm. In the BSA-based arm, 60 mg/m(2) of docetaxel was administered. In the individualized arm, individualized doses of docetaxel were calculated from the estimated clearance (estimated clearance = 31.177 + [7.655 x 10(-4) x total 6-beta-OHF] - [4.02 x alpha-1 acid glycoprotein] - [0.172 x AST] - [0.125 x age]) and the target AUC of 2.66 mg/L . h. RESULTS: In the individualized arm, individualized doses of docetaxel ranged from 37.4 to 76.4 mg/m(2) (mean, 58.1 mg/m(2)). The mean AUC and standard deviation (SD) were 2.71 (range, 2.02 to 3.40 mg/L . h) and 0.40 mg/L . h in the BSA-based arm, and 2.64 (range, 2.15 to 3.07 mg/L . h) and 0.22 mg/L . h in the individualized arm, respectively. The SD of the AUC was significantly smaller in the individualized arm than in the BSA-based arm (P < .01). The percentage decrease in absolute neutrophil count (ANC) averaged 87.1% (range, 59.0 to 97.7%; SD, 8.7) in the BSA-based arm, and 87.4% (range, 78.0 to 97.2%; SD, 6.1) in the individualized arm, suggesting that the interpatient variability in percent decrease in ANC was slightly smaller in the individualized arm. CONCLUSION: The individualized dosing method based on the total amount of urinary 6-beta-OHF after cortisol administration can decrease PK variability of docetaxel.

Aged↗

PubMed2005

Phase II trial of postoperative adjuvant cisplatin and etoposide in patients with completely resected stage I-IIIa small cell lung cancer: the Japan Clinical Oncology Lung Cancer Study Group Trial (JCOG9101).

OBJECTIVE: Indications for surgical intervention for very limited small cell lung cancer have not yet been determined. The objective of this study is to determine whether resection followed by cisplatin and etoposide is feasible. METHODS: From September 1991 through December 1996, 62 patients with completely resected small cell lung cancer who were less than 76 years of age from 17 centers were entered in the trial. Of 62 patients, 61 were eligible, with a median follow-up of 65 months. Chemotherapy consisted of 4 cycles of cisplatin (100 mg/m 2 , day 1) and etoposide (100 mg/m 2 , days 1-3). There were 49 (80%) male patients, 44 with clinical stage I disease, 10 with stage II disease, and 6 with stage IIIa disease. RESULTS: Forty-two (69%) patients received 4 cycles of cisplatin and etoposide. No treatment-associated mortality was noted. Median survival time was not reached in patients with pathologic stage I disease, was 449 days in patients with stage II disease, and was 712 days in patients with stage IIIa disease. Three-year survival was 61% overall, 68% in patients with clinical stage I disease, 56% in patients with stage II disease, and 13% in patients with stage IIIa disease ( P = .02). Recurrence was noted in 26 (43%) patients overall. Local failure was noted in 6 (10%) patients. Locoregional recurrence tends to be found more frequently in patients with stage IIIA disease. Distant failure was found in 21 (34%) patients overall. Brain metastasis was found in 15% of the patients. CONCLUSION: Major lung resection followed by postoperative cisplatin and etoposide is feasible, with a favorable survival profile. Because nodal metastasis appears to be a major prognostic factor, preoperative evaluation of nodal status remains a major concern.

Adult↗

PubMed2005

Randomized controlled trial to evaluate radiotherapy +/- endocrine therapy versus endocrine therapy alone for PSA failure after radical prostatectomy: Japan Clinical Oncology Group Study JCOG 0401.

A randomized controlled trial has started in Japan to evaluate radiotherapy and endocrine therapy for prostate-specific antigen (PSA) failure after radical prostatectomy. Patients who have PSA failure after radical prostatectomy for localized prostate cancer (T1-2N0M0) are randomized into treatment groups of either radiotherapy +/- endocrine therapy or endocrine therapy alone. The Urologic Oncology Study Group (UOSG) in the Japan Clinical Oncology Group (JCOG) composed of 36 specialized institutions will recruit 200 patients. The primary end-point is time to treatment failure (TTF) of bicalutamide, and secondary end-points are TTF of protocol treatment, progression-free survival, overall survival, adverse events and quality of life (QOL). The Clinical Trial Review Committee of the JCOG approved the protocol on April 13, 2004, and the study was activated on May 17, 2004.

Adult↗

PubMed2005

Standard thoracic radiotherapy with or without concurrent daily low-dose carboplatin in elderly patients with locally advanced non-small cell lung cancer: a phase III trial of the Japan Clinical Oncology Group (JCOG9812).

BACKGROUND: The purpose of this study was to evaluate whether radiotherapy with carboplatin would result in longer survival than radiotherapy alone in elderly patients with unresectable stage III non-small cell lung cancer (NSCLC). METHODS: Eligible patients were 71 years of age or older with unresectable stage III NSCLC. Patients were randomly assigned to the radiotherapy alone (RT) arm, irradiation with 60 Gy; or the chemoradiotherapy (CRT) arm, the same radiotherapy and additional concurrent use of carboplatin 30 mg/m(2) per fraction up to the first 20 fractions. RESULTS: This study was terminated early when 46 patients were registered from November 1999 to February 2001. Four patients (one in the RT arm, three in the CRT arm) were considered to have died due to treatment-related causes. The JCOG Radiotherapy Committee assessed these treatment-related deaths (TRDs) and the compliance with radiotherapy in this trial. They found that 60% of the cases corresponded to protocol deviation and 7% were protocol violation in dose constraint to the normal lung, two of whom died due to radiation pneumonitis. As to the effectiveness for the 46 patients enrolled, the median survival time was 428 days [95% confidence interval (CI) = 212-680 days] in the RT arm versus 554 days (95% CI = 331 to not estimable) in the CRT arm. CONCLUSIONS: Due to the early termination of this study, the effectiveness of concurrent use of carboplatin remains unclear. We re-planned and started a study with an active quality control program which was developed by the JCOG Radiotherapy Committee.

Aged↗

PubMed2005

[Impact of the change in criteria for hospital discharge of patients with tuberculosis based on the duration of hospitalization].

OBJECTIVES: The criteria for discharge from TB ward was changed from sputum culture negative to smear negative since January 2003 and the duration of hospitalization and the applicability of each criteria were analyzed. METHODS: Cases hospitalized from Jan. to Dec. 2003 (Group I) were compared with those hospitalized from Jan. 2000 to Dec. 2002 (Group II). In group I, we investigated which criteria was applied for each case. RESULTS: Shifting criteria from culture negative to smear negative, the median duration of hospitalization was shortened from 83 to 70 days, in particular in 20s, 30s and 70s. No effect however were found in patients with initially high grade excreter of AFB or extensive cavitary lesions. Although 44% of patients were discharged according to smear conversion to negative, this criteria could not be applied in 17% due to some reasons. CONCLUSIONS: Conversion to culture negative has been conventionally used for discharge criteria in Japan considering not only contagiousness of the disease but to maintain patients adherence to treatment. After the introduction of new criteria to shorten the hospitalization periods, Japanese style DOTS after discharge would be more important to maintain patients adherence to treatment. We will continue to evaluate the treatment completion rate.

Adult↗

PubMed2004

Feasibility study of neoadjuvant chemotherapy followed by interval cytoreductive surgery for stage III/IV ovarian, tubal and peritoneal cancers: Japan Clinical Oncology Group Study JCOG0206.

A feasibility study was started in January 2003 on neoadjuvant chemotherapy (NAC) followed by interval cytoreductive surgery (ICS) and postoperative chemotherapy for stage III/IV müllerian carcinomas such as ovarian, tubal and peritoneal carcinomas. The purpose is to assess the safety and efficacy of the treatment starting with NAC and also to know whether we can accurately diagnose these advanced carcinomas by imaging studies, cytologic findings and tumor markers without staging laparotomy or laparoscopy. Fifty-six patients with advanced müllerian carcinomas will be recruited to the study. After confirmation of diagnosis by laparoscopic inspection and biopsies, patients undergo four cycles of chemotherapy as NAC, followed by ICS and an additional four cycles of post-surgical chemotherapy. The primary endpoint is proportion of clinical complete remission after accomplishment of the protocol treatment, while the major secondary endpoint is positive predictive value of diagnosis before laparoscopy regarding tumor origin, histology and stage. Based on the results of this study, we will conduct a phase III study to compare the treatment starting with NAC and primary cytoreductive surgery followed by post-surgical chemotherapy.

Adult↗

PubMed2004

A randomized controlled trial investigating the survival benefit of dose-intensified multidrug combination chemotherapy (LSG9) for intermediate- or high-grade non-Hodgkin's lymphoma: Japan Clinical Oncology Group Study 9002.

The effect of enhancing the dose intensity (DI) of the key drugs in multidrug combination chemotherapy for malignant lymphoma is uncertain. We investigated the survival benefit of dose-intensified multidrug combination chemotherapy for intermediate- or high-grade non-Hodgkin's lymphoma (NHL). Patients without any prior chemotherapy were randomly assigned either to dose-intensified multidrug combination chemotherapy, LSG9 (VEPA-B/FEPP-AB/M-FEPA, treated 3 times every 10 weeks for 28 weeks total), or to control-arm combination chemotherapy, mLSG4 (VEPA-B/FEPP-B/M-FEPA, treated 4 times every 14 weeks for 54 weeks total). The planned DI of doxorubicin and cyclophosphamide were 1.96 and 1.47 times higher, respectively, in LSG9 than in mLSG4. Overall survival, complete response (CR) rate, and toxicities were evaluated. The 447 patients (230 for LSG9 and 217 for mLSG4) were enrolled between February 1991 and March 1995. The 5-year overall survival rates were 56.8% for LSG9 patients and 55.1% for mLSG4 patients (log-rank P = .42). The rates for CR plus uncertain CR were 70.0% for LSG9 and 64.5% for mLSG4. The toxicities of both regimens were similar and tolerable. The median actual DI of doxorubicin and cyclophosphamide were 1.56 and 1.17 times higher, respectively, in LSG9 than in mLSG4. Compared with the control regimen mLSG4, the dose-intensified regimen LSG9 did not show significant survival benefit. An increase in the DI of doxorubicin in multidrug combination chemotherapy did not improve the survival of patients with intermediate- or high-grade NHL.

Adolescent↗

PubMed2003

Long-term follow-up of patients with unresectable locally advanced non-small cell lung cancer treated with chemoradiotherapy: a retrospective analysis of the data from the Japan Clinical Oncology Group trials (JCOG0003A).

To clarify the long-term survival data and factors that are correlated with survival outcome of unresectable locally advanced non-small cell lung cancer (NSCLC) following chemoradiotherapy, we analyzed patients who entered the Japan Clinical Oncology Group (JCOG) clinical trials for unresectable locally advanced NSCLC. Between October 1989 and August 1997, 240 patients (male 207, female 33; PS (performance status) 0 58, PS 1 172, PS 2 9, unknown 1; stage IIB 2, IIIA 62, IIIB 175, unknown 1) entered the 6 trials. All patients received chemotherapy and radiotherapy. The associations between survival outcome and treatment-related factors were analyzed using Cox regression analysis. Median survival times and 5-year survival rates in the trials were 11.9-19.7 months and 0-17.6%, respectively. Median survival time was 16.1 months and the 5- and 7-year survival rates of all 240 patients were 14.4% and 12.0%, respectively. No deaths were observed 7 years after initiation of the treatment or later. For stage IIIA and IIIB patients, the 5-year survival rates were 16.3% and 13.4%, respectively. Node status and age were significantly associated with survival, but no factors of the treatment were associated with survival of patients with unresectable locally advanced NSCLC. The present retrospective analysis showed that approximately 12% of patients with unresectable locally advanced NSCLC could be cured by various chemoradiotherapy regimens.

Adult↗

PubMed2003

[Time-to-event endpoints--definitions and methodological issues].

Time-to-event endpoint or survival time is the most important type of endpoint that is widely used in clinical cancer research. Understanding the principles of event definition, censoring and possible biases by competing risks is critical to obtain the unbiased estimates of time-to-event endpoints. The authors provide the standard definitions, characteristics, and pitfalls of several major time-to-event endpoints, such as overall survival, progression-free survival, relapse-free survival, disease-free survival, and time to treatment failure.

Biomedical Research↗

PubMed2002

Phase II study of twice-daily high-dose thoracic radiotherapy alternating with cisplatin and vindesine for unresectable stage III non-small-cell lung cancer: Japan Clinical Oncology Group Study 9306.

PURPOSE: To evaluate the efficacy and toxicity of high-dose thoracic radiotherapy (TRT) alternating with chemotherapy (CH) for unresectable stage III non--small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Forty-one patients received TRT with 1.5 Gy twice daily, 5 days a week, on weeks 1, 2, 5, 6, and 9, up to a total dose of 66 to 72 Gy, alternating with cisplatin 80 mg/m(2) on day 1 and vindesine 3 mg/m(2) on days 1 and 8, repeated every 4 weeks, for two or three courses beginning on week 3. RESULTS: The median (range) total dose of TRT and number of CH courses were 72 Gy (16.5 to 72 Gy) and three (zero to three), respectively. Delay in TRT > or = 5 days was observed in 24 (75%) of 32 patients who completed the projected treatment, due to leukopenia in 12, esophagitis in seven, infection in two, and other causes in three patients. Partial responses were obtained in 36 patients (88%). The median survival time and 3- and 5-year survival rates were 18.4 months, 24%, and 10%, respectively. Grade 3 or 4 leukopenia and esophagitis developed in 32 and seven patients, respectively. Grade 3 or 4 late esophageal toxicity developed in two patients. CONCLUSION: Alternating high-dose TRT and CH for stage III NSCLC produced a high response rate with median and long-term survival comparable to prior trials utilizing standard approaches in this population. Acute and late esophageal toxicity was observed and interruption of TRT was required in most of the patients.

Antineoplastic Agents↗

PubMed2002

The Influence of handling censored data on estimating progression-free survival in cancer clinical trials (JCOG9913-A).

BACKGROUND: Progression-free survival (PFS) is a common endpoint in cancer clinical trials. This study was undertaken to assess the impact of data errors and data handling on the statistical estimation of PFS. METHODS: Data from four trials conducted by the Japan Clinical Oncology Group were examined. Three types of data handling methods were defined: (1) data handling method A (METHOD-A), the collected event data are used as much as possible, (2) METHOD-C, only reliable data with firm evidence are used, and (3) METHOD-B is intermediate between METHOD-A and METHOD-C. To assess the impact of each of the three methods, Kaplan-Meier survival curves, median PFS, proportion of PFS, log-rank p values and hazard ratios were estimated. RESULTS: In three trials that collected PFS data periodically, no remarkable differences in median PFS and the proportion of PFS were observed. In one trial with non-periodic data cleaning, however, the ratio of median PFS by METHOD-C to that by METHOD-B was 0.85, the maximum difference of proportion of PFS between METHOD-C and METHOD-B was 12.0% and the largest spread in PFS curves amongst the three methods was observed in this trial. In all trials, log-rank p values and hazard ratios for between arm comparisons did not differ between the three methods. CONCLUSIONS: Periodic data management can reduce errors in comparisons of PFS and is a critical requirement when using PFS as a major endpoint. Furthermore, proper data handling is essential in the estimation of patient benefit and caution is needed when making clinical decisions based on PFS.

Clinical Trials as Topic↗

PubMed2002

[Hepatic recurrence after prophylactic hepatic arterial infusion of 5-fluorouracil for Dukes' C colorectal cancer--correlation with the expression of dihydropyrimidine dehydrogenase in the primary tumor].

PURPOSE: The purpose of this study was twofold: (1) to disclose the intermediate outcome of a non-randomized trial of prophylactic hepatic arterial infusion chemotherapy (PHAI) for curatively resected Dukes' C colorectal cancer performed between November 1996 and April 2000, and (2) to examine the relationship between the expression of dihydropyrimidine dehydrogenase (DPD) in tumor tissue and the efficacy of this chemotherapy. PATIENTS AND METHODS: The oncological outcomes were compared between patients (n = 28) receiving PHAI (5-FU: 500 mg/body/w x 50 cycles) plus oral administration of UFT-E (400 mg/body/day, for 24 months) and those (n = 21) receiving UFT-E alone. The levels of tumoral DPD were determined in a total of 43 patients (n = 25, PHAI group; n = 18, control group) by an enzyme-linked immunosorbent assay. RESULTS: Seven (25%) in the PHAI group and four (19%) in the control group developed liver metastasis postoperatively. The liver metastasis-free survival was not different between the groups (p = 0.94). When the analysis was restricted to patients who developed liver metastasis, the duration from surgery to detecting liver metastasis tended to be longer in the PHAI group (p = 0.09). In addition, the overall survival tended to be better in the PHAI group (p = 0.12). In the control group, the level of DPD was higher in patients who developed liver metastases (n = 4) than in those who did not (n = 14, p = 0.04). However, in the PHAI group, the level of DPD was not different regardless of the occurrence of liver metastases (p = 0.30). CONCLUSIONS: These results suggest that (1) PHAI is unlikely to improve the prognosis of Dukes' C patients remarkably, and (2) the efficacy of this regimen cannot be predicted by determining the levels of tumoral DPD.

Administration, Oral↗