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Yasuo Ohashi

Publications and source records attributed to Yasuo Ohashi.

At least 73 records · Page 4Linked to original sources
PubMed2004

Statistical comparison of random allocation methods in cancer clinical trials.

The selection of a trial design is an important issue in the planning of clinical trials. One of the most important considerations in trial design is the method of treatment allocation and appropriate analysis plan corresponding to the design. In this article, we conducted computer simulations using the actual data from 2158 rectal cancer patients enrolled in the surgery-alone group from seven randomized controlled trials in Japan to compare the performance of allocation methods, simple randomization, stratified randomization and minimization in relatively small-scale trials (total number of two groups are 50, 100, 150 or 200 patients). The degree of imbalance in prognostic factors between groups was evaluated by changing the allocation probability of minimization from 1.00 to 0.70 by 0.05. The simulation demonstrated that minimization provides the best performance to ensure balance in the number of patients between groups and prognostic factors. Moreover, to achieve the 1 percentile for the p-value of chi-square test around 0.50 with respect to balance in prognostic factors, the allocation probability of minimization was required to be set to 0.95 for 50, 0.80 for 100, 0.75 for 150 and 0.70 for 200 patients. When the sample size was larger, sufficient balance could be achieved even if reducing allocation probability. The simulation using actual data demonstrated that unadjusted tests for the allocation factors resulted in conservative type I errors when dynamic allocation, such as minimization, was used. In contrast, adjusted tests for allocation factors as covariates improved type I errors closer to the nominal significance level and they provided slightly higher power. In conclusion, both the statistical and clinical validity of minimization was demonstrated in our study.

Aged↗
PubMed2004

Statistical evaluation of the diagnostic accuracy of methods used to determine the progression of visual field defects in glaucoma.

OBJECTIVE: To evaluate trend-type analyses to judge the progression of visual field damage (VFD) of glaucoma in terms of ratios of making judgments of progression and specificity, and to report a new method. DESIGN: Retrospective analysis of visual field (VF) results of actual glaucoma cases and those simulated by computer, and receiver operating characteristic curve analysis of performance of methods to judge the progression of VFD. PARTICIPANTS: One hundred five eyes of 105 open-angle glaucoma (OAG) patients with progressing VFD and 355 eyes of 355 clinically stable OAG patients for VF simulation from 4 university-based referral practices. METHODS: Methods using regression analysis of total deviation (TD), mean deviation (MD), mean TD of a sectored VF, and original scoring used in the Advanced Glaucoma Intervention Study (AGIS) were compared. A VF test was repeated twice in a short period on the 355 stable OAG eyes, and test-retest fluctuation, including variance at each test point and covariance between 2 test points, was calculated to simulate stable glaucomatous VF series by computer. The sensitivity of each method was calculated with 105 progressing VF series, and specificity was calculated with 10,000 simulated stable glaucomatous VF series. MAIN OUTCOME MEASURES: Sensitivity (ratios of making judgments of progression), specificity, and diagnostic power. RESULTS: The methods using the TD slope on one test location showed a sensitivity of 0.848 to 1.000, with a specificity of 0.105 to 0.721, and on 2 adjacent test locations showed a sensitivity of 0.848, with a specificity of 0.722. A significant negative MD slope with P<0.05 showed a sensitivity of 0.524, with a specificity of 0.945. The method using a sectored VF showed a sensitivity of 0.695, with a high specificity of 0.946. The AGIS method showed a sensitivity of 0.305 to 0.467, with a very high specificity of 0.999 to 1.000. The method using previously reported mathematically sectored VFs showed a sensitivity of 0.790, with a specificity of 0.900, and higher diagnostic power (1.69) than the others in this study population. CONCLUSIONS: Most of the methods using the TD slope were characterized by high sensitivity, the AGIS method had a very high specificity, and those using VF sectors had reasonable sensitivity and specificity.

Adolescent↗
PubMed2004

A randomized, open-label, comparative study of simvastatin plus diet versus diet alone on angiographic retardation of coronary atherosclerosis in adult Japanese patients: Japanese utilization of simvastatin therapy (JUST) study.

BACKGROUND: Cholesterol-lowering therapy reduces the risk of cardiovascular events by slowing the progression or enhancing the regression of coronary atherosclerosis. OBJECTIVE: This study assessed the effects of simvastatin 10 mg/d on progressive coronary atherosclerosis in Japanese patients with coronary artery disease and mild to moderate hypercholesterolemia. METHODS: In a 2-year, open-label comparative study, patients with coronary atherosclerotic lesions (> or =50% diameter stenosis) and serum total cholesterol levels > or =200 and < or =280 mg/dL were randomly assigned to 2 groups: 1 group received simvastatin 10 mg/d taken orally with diet (S-D) and the other group was assigned to diet alone (D). Atherosclerotic progression in coronary segments was compared in the 2 groups using quantitative coronary angiography (QCA). QCA measurements were done under blinded conditions. The study's primary end point was the comparison of mean changes in each segment's minimum obstruction diameter (MOD) or mean segment diameter (MSD) between the S-D group and the D group. RESULTS: A total of 299 patients were randomized, 146 to the S-D group and 153 to the D group. Mean (SD) age was 58.7 (8.0) years and mean (SD) total cholesterol level was 232.6 (21.6) mg/dL at baseline. After 2 years, serum low-density lipoprotein cholesterol levels decreased by 31.9% in the S-D group and by 2.0% in the D group. QCA showed significant stenotic progression in the D group, with reductions in MOD and MSD both by per-segment-based (P < 0.001 and P = 0.004, respectively) and per-patient-based (both P = 0.004) analyses. Although simvastatin treatment suppressed atherosclerotic progression in both per-segment- and per-patient-based analyses, significant reductions were found only in MOD values with per-segment-based analyses (P = 0.034). In a categorical approach, progression was found in significantly fewer segments in the S-D group compared with the D group (MOD, P = 0.014; MSD, P = 0.003), with odds ratios (S-D) group/D group) of 0.571 for MOD and 0.390 for MSD. Significantly fewer patients with angiographic progression were observed in the S-D group (23.3%) compared with the D group (39.4%) with respect to MSD (P = 0.02). CONCLUSION: Two years of treatment with simvastatin 10 mg/d improved patients' lipid profile and retarded coronary atherosclerotic progression in Japanese patients with coronary artery disease and mild to moderate hypercholesterolemia

Anticholesteremic Agents↗
PubMed2004

Superior anti-tumor efficacy of bicalutamide 80 mg in combination with a luteinizing hormone-releasing hormone (LHRH) agonist versus LHRH agonist monotherapy as first-line treatment for advanced prostate cancer: interim results of a randomized study in Japanese patients.

OBJECTIVES: To evaluate bicalutamide (Casodex) 80 mg as a component of maximum androgen blockade (MAB) in Japanese patients with previously untreated advanced prostate cancer. METHODS: 205 patients with previously untreated stage C/D prostate cancer were randomized (1:1) to receive once-daily bicalutamide 80 mg or placebo, each combined with a luteinizing hormone-releasing hormone (LHRH) agonist. Primary study variables were the 12 week prostate-specific antigen (PSA) normalization (i.e. PSA level <or=4 ng/ml) rate, the 12 week overall tumor response rate (proportion with a partial response or better) and the proportion of withdrawals due to adverse drug reactions (ADRs) at follow-up. This interim analysis was undertaken after a minimum of 6 months' follow-up (median 15 months). RESULTS: The 12 week PSA normalization rate was 79.4% for MAB and 38.6% for LHRH agonist monotherapy (P < 0.001). The 12 week overall tumor response rate was 77.5 and 65.3%, respectively (P = 0.063). The withdrawal rate due to ADRs was 8.8% and 10.9%, respectively. There were differences in favor of MAB over monotherapy with respect to time to treatment failure (TTTF) (P = 0.038) and time to progression (TTP) (P = 0.016). There have been too few deaths (n = 10) to analyze survival. The profiles of adverse events and ADRs were broadly similar in the two treatment groups. CONCLUSION: In Japanese patients with advanced prostate cancer, first-line treatment with bicalutamide 80 mg in combination with an LHRH agonist is superior to LHRH agonist monotherapy in terms of the antitumor response at 12 weeks, and also time to treatment failure and progression, and does not compromise treatment safety. The study is ongoing.

Aged↗
PubMed2004

Phase I/II study of combination therapy of oral fluorinated pyrimidine compound S-1 with low-dose cisplatin in patients with unresectable and/or recurrent advanced gastric cancer: a novel study design to evaluate safety and efficacy.

A phase I/II clinical trial has been planned to evaluate the safety and efficacy of combination therapy of S-1 with low-dose cisplatin in patients with unresectable or recurrent gastric cancer. A new statistically as well as clinically deliberated study design is applied to determine the maximal benefits of combination chemotherapy. This trial uses a 'continual reassessment method' for evaluating toxicity and a "two-stage method" for assessing the response rate to determine the combination that achieves adequate tumor response without toxicity in a high proportion of patients. Three specialized institutions will recruit 10-16 patients for the phase I part of the trial, and 14 institutions, in conjunction with the three specialized ones, will enroll 42 patients for the phase II part. The goal of this trial is to establish a useful chemotherapeutic treatment in an outpatient setting.

Administration, Oral↗
PubMed2004

Endocrine therapy with or without radical prostatectomy for T1b-T3N0M0 prostate cancer.

BACKGROUND: We retrospectively compared the 5-year survival rates of T1b-T3N0M0 prostate cancer patients treated either by endocrine therapy plus radical prostatectomy or endocrine therapy alone. METHODS: Clinical T1b-T3N0M0 prostate cancer patients were enrolled at 104 institutions in Japan. They were assigned to study 1 (n = 176), if they were indicated to prostatectomy, if not indicated, they were assigned to study 2 (n = 151). The indication of prostatectomy was based on the clinical judgement of physicians and/or patients. Those assigned to study 1 underwent prostatectomy and adjuvant endocrine therapy with or without preoperative androgen deprivation. Those assigned to study 2 were treated with leuprorelin acetate with or without chlormadinone acetate. They were followed-up every 3 months until death or for 5 years and over. RESULTS: Those assigned to study 1 were younger (mean age 67.2 vs 75.7 years), less advanced in clinical stage, and had lower prostate specific antigen levels (mean 43.8 vs 103.6 ng/mL). Death for any reason was observed less frequently in study 1 (n = 29, 16%) than study 2 (n = 50, 33%), and the 5-year overall survival rate was higher in study 1 (87 vs. 68%). However, prostate cancer deaths were comparatively seldom (9% in study 1 and 7% in study 2), resulting in the identical 5-year cause specific survival rate in both study groups (91%). In both study groups the overall survival was almost equal to the natural survival of age-matched men. CONCLUSIONS: Endocrine therapy offers a reasonable survival rate in T1b-T3 prostate cancer patients within a 5-year follow-up. Observation will be extended to determine 10-year outcomes.

Age Factors↗
PubMed2004

Radical prostatectomy and adjuvant endocrine therapy for prostate cancer with or without preoperative androgen deprivation: Five-year results.

BACKGROUND: The effects of preoperative androgen deprivation on the outcomes of prostate cancer patients who received radical prostatectomy and subsequent adjuvant endocrine therapy have not yet been fully evaluated. METHODS: Patients with stage A(2), B or C prostate cancers were randomized to one of two groups: group I (n = 90), who received androgen deprivation (leuprolide and chlormadinone acetate) for 3 months followed by radical prostatectomy and subsequent adjuvant endocrine therapy (leuprolide alone), and group II (n = 86), who underwent the surgery followed by 3-month androgen deprivation (leuprolide and chlormadinone acetate) and subsequent adjuvant endocrine therapy (leuprolide alone). The effects of preoperative androgen deprivation on survival, clinical relapse (serum prostate specific antigen, PSA, above the normal level, local recurrence, or distant metastases), and PSA relapse (PSA above the detectable level) were evaluated at 5 years or later after treatment. RESULTS: There were no significant differences in overall, cause-specific, clinical relapse-free, or PSA relapse-free survival rates between the two groups. In a subanalysis, no prostate cancer deaths or clinical relapses were noted in 29 patients with organ-confined disease (OCD: negativity of capsular invasion, seminal vesicle invasion, surgical margins or nodal involvement). The odds ratio for OCD depending on group assignment was 2.44 (95% confidence interval, CI 1.04-5.72), for group I, demonstrating a higher probability of having OCD. This ratio was increased to 4.00 (95% CI 1.06-15.16) if the analysis was conducted in a subpopulation with prostate specific antigen levels less than 35.6 ng/mL and with clinical stage B or C cancers. CONCLUSION: Preoperative androgen deprivation has no demonstrable benefit in 5-year outcomes for patients undergoing radical prostatectomy and adjuvant endocrine therapy. However, it did increase the probability of OCD, which was associated with no clinical relapse during the follow-up. A longer observation is needed to clarify the exact extent of the benefits in terms of survival.

Aged↗
PubMed2004

Dose-response study of 22-oxacalcitriol in patients with secondary hyperparathyroidism.

The dose-response relationships and the safety of administering 22-oxacalcitriol (OCT) to patients with secondary hyperparathyroidism (2HPT) under regular three-times-weekly hemodialysis (HD) were evaluated by double-blind parallel group design. A total of 203 patients with 2HPT were randomly allocated into four groups, and 5 microg (Group L), 10 microg (Group M), or 15 microg (Group H) OCT, or placebo (Group P) was administrated at the end of every HD for 12 weeks. Reductions of intact-parathyroid hormone (iPTH) concentration greater than 30% from baseline were observed in 7.7% of Group P as compared to 77.3% of the pooled OCT groups after 12 weeks of treatment (Mantel test: P < 0.001). Time-trends (slopes) of log-iPTH concentration calculated by least-squares line fitting to each patient's data during treatment differed between Group P and the pooled OCT groups (t-test: P < 0.001) and these iPTH slopes decreased dose-dependently (linear trend by t-test: P < 0.001). Slopes of serum calcium corrected for albumin (corrected-sCa) concentrations also differed between Group P and the pooled OCT groups (t-test: P < 0.001), and increased dose-dependently (linear trend by t-test: P < 0.0001). Serum phosphorus and Ca x P product increased significantly only in high dose groups. Slopes of log(iPTH) and corrected-sCa concentrations were reciprocally related. Most adverse events were hypercalcemia and dose-related, but occasionally comprised pruritus or increased serum creatinine phosphokinase. These results indicate that OCT produced a strong and dose-dependent suppression of PTH and an increase of corrected-sCa concentration in patients with 2HPT. The recommended initial dosages of OCT would appear to be 5 microg when pretreatment iPTH concentrations are less than 500 pg/mL, and 10 microg when greater than 500 pg/mL for safe and effective treatment. As in the case of PTH, calcium and phosphorus showed dose-dependent increases. It is therefore essential to take precautions as to possible increases in calcium and phosphorus.

Acid Phosphatase↗
PubMed2004

Durable response but prolonged cytopenia after cladribine treatment in relapsed patients with indolent non-Hodgkin's lymphomas: results of a Japanese phase II study.

We conducted a phase II study to evaluate the efficacy and safety of cladribine (2-chlorodeoxyadenosine [2-CdA]) for patients with refractory or relapsed indolent B-cell lymphoma or mycosis fungoides. Forty-five patients were enrolled, and 43 patients, including 34 with follicular lymphoma, were eligible. 2-CdA was given by continuous intravenous infusion at a dose of 0.09 mg/kg daily for 7 consecutive days, and this schedule was repeated every 4 weeks up to a maximum of 6 cycles. The overall and complete response rates were 58.1% (25/43; 90% confidence interval, 44.5%-70.9%) and 14.0% (6/43), respectively. The disease progression-free proportions of all 43 eligible and all 25 responding patients at 2 years were 30.3% and 48.1%, respectively. Neutropenia and thrombocytopenia of grade 3 or 4 were observed in 53.3% and 37.8% of patients, respectively, with prolonged cytopenia observed in patients with increased numbers of treatment cycles. Nonhematologic toxicities of grade 3 or greater included diarrhea, arrhythmia, malaise, and gastrointestinal bleeding in 1 patient each, an increase in glutamic-pyruvic transaminase level in 2 patients, and infection in 5 patients. Two treatment-related deaths were observed. Four patients developed myelodysplastic syndrome (MDS) at 13 months to 2 years after completion of the 2-CdA treatments. 2-CdA is an active agent with acceptable toxicity for refractory or relapsed indolent lymphoma; however, prolonged myelosuppression and the potential development of MDS should be carefully monitored.

Adult↗
PubMed2004

[Molecule based diagnosis].

Based on reviews of the concept of diagnostics and in general and in specific tumour areas it was clear that development of diagnostic procedures involving genomics will allow for much better targeted and tailored treatments in the future. This will result in better efficacy and better tolerability of cancer treatments, but will also allow for progress in prediction, diagnosis and dose selection. Large collaborative projects studying the efficacy and safety of drugs on the genome level is promising to bring important benefits to both patients and the national economy by reducing useless drug therapy. In colorectal cancer there are several genetic defects identified that can act as the target for directed therapy in the future. Expressions of tumour specific antigens open the way for immunological targeted therapies. Developments in the understanding of the genomic basis for resistance to anti-tumour therapy is promising to help targeting patients likely to respond and not develop resistance. A Japanese model is being developed to determine the relative risk of breast cancer of Japanese women. Based on this prevention therapies can be instigated. The last four years have seen the introduction of four novel targeted therapies. If this model should become a standard in the future, much stronger collaboration between academic research and pharmaceutical industry need to develop.

Antineoplastic Agents↗
PubMed2004

[Anti angiogenesis].

Based on presentations on the basic concepts and scientific rationale of anti-angiogenic approaches to cancer therapy and the possible applications in the area of prostate cancer, gastrointestinal cancer, lung cancer and breast cancer it is easy to conclude that development of anti-angiogenic approaches into clinical therapies is extremely challenging. It is now well established that cancer growth is increased by angiogenic factors and that inhibition of angiogenesis decreases growth and metastatic potential. Anti-angiogenic effect can be obtained through interference with multiple targets. Further development of new strategies involving such novel cancer therapies requires wide reaching development of translational research abilities. However, for moving new therapies into the clinic same rigorous criteria need to be applied as is done for traditional therapies. Angiogenesis appear to be a critical factor for development of prostate, gastric, lung and breast cancers. Development of new anti-angiogenic treatment modalities might become very important in these diseases. A critical requirement for the successful clinical development will be the development of imaging techniques that can help evaluate the effect on blood vessel functionality. Such surrogate markers of anti-angiogenic effect will be essential for optimising molecules and doses.

Angiogenesis Inhibitors↗
PubMed2004

[Prevention and therapeutic strategy of metabolic syndrome--implications from the interim results of Japan Diabetes Complications Study(JDCS)].

Type 2 diabetes plays significant roles in pathogenesis of metabolic syndrome. The Japan Diabetes Complications Study(JDCS) is an ongoing trial with 2,205 patients with type 2 diabetes. It is clarified that the frequencies of CHD and stroke events in type 2 diabetic patients are three or more times greater than non-diabetic subjects. Gender, LDL cholesterol, glycohemoglobin A1c and triglycerides are significant age-adjusted risk factors for CHD in patients with type 2 diabetes, while systolic blood pressure and glycohemoglobin A1c are those for stroke. We can conclude from these results that the control of risk factors like LDL cholesterol and blood pressure, together with glycemic control, is essential for preventing CHD and stroke also in Japanese patients with type 2 diabetes.

Cardiovascular Diseases↗
PubMed2004

[Validity and clinical applicability of the Japanese version of amyotrophic lateral sclerosis--assessment questionnaire 40 (ALSAQ-40)].

We studied validity and clinical applicability of the Japanese version of amyotrophic lateral sclerosis (ALS) assessment questionnaire 40 (ALSAQ-40). The original version contains forty questions measuring five areas (domains) of health status: Physical Mobility, ADL/Independence, Eating and Drinking, Communication and Emotional Functioning. Data were obtained from 39 ALS patients and from their physicians at 15 centers in Japan. Patients completed the ALSAQ-40 and the SF-36, and provided information on their age and their status of ventilator use. Their physicians provided information on the date of diagnosis, type of disease and clinical characteristics, and ALSFRS-R. The patients' average age was 58.5 years, and 64% were men. The mean duration since diagnosis was 39.1 months. Forty four percent were classical ALS patients and 46% were receiving a respiratory intervention. Although there was much heterogeneity, the scores for Physical Mobility and ADL/Independence were higher(indicating worse health status)than the scores for the other domains. Item-scale correlations were strong, except for the item "felt embarrassed in social situations" in the Emotional Functioning domain. All the domains had very high internal consistency: Cronbach's alphas ranged 0.95 to 0.97. With regard to the cluster structure of the forty items, the Eating and Drinking domain and the Communication clustered together. The reason might be that the former consisted of only three items and both domains measure bulbar symptoms. Domain scores correlated significantly with scores of related dimensions in the SF-36 and ALSFRS-R, and did not correlate strongly with unrelated domains. The five items of the ALSAQ-5 correlated with all five domain scores on the ALSAQ-40. These results should be interpreted with caution because we analyzed together data from ALS patients with various characteristics. In conclusion, although we may need to add and remove some items and modify the wording of others, the Japanese version of the ALSAQ-40 had high validity and is likely to be useful in evaluating of QOL in ALS patients. Whether the ALSAQ-5 can be used in place of the ALSAQ-40 is a matter for further study.

Activities of Daily Living↗
PubMed2004

[Reliability at the National Cancer Institute-Common Toxicity Criteria version 2.0].

We evaluated the reliability of CTC v 2.0 based on source documents and also studied the degree of inconsistency in toxicity grading. Five clinical research coordinators from the National Cancer Center Hospital independently reviewed source documents from 17 patients and graded toxicities in the following common adverse events: diarrhea, nausea, stomatitis/pharyngitis, vomiting, febrile neutropenia, infection, infection unknown source, and sensory neuropathy. If grading was already documented on the medical chart, it was masked so that the coordinator could perform the evaluation without information bias. After the completion of toxicity grading, the participating coordinators discussed each case, and a consensus was reached for final toxicity grading. The proportion of agreement for each toxicity criteria are as follows: diarrhea; 0.59 (95%CI 0.35-0.82), nausea; 0.47 (0.23-0.71), stomatitis/pharyngitis; 0.59 (0.35-0.82), vomiting; 0.71 (0.49-0.92), febrile neutropenia; 0.88 (0.73-1.04), infection; 0.82 (0.64-1.01), infection by unknown source; 0.82 (0.64-1.01), sensory neuropathy; 0.65 0.42-0.87). The cause of variability largely depended on the differences in individual clinical assessment, and misunderstanding of toxicity criteria by coordinators has been observed. Even in a single institution environment, variability exists in the toxicity assessment and grading. Good training and education on toxicity assessment using common criteria and development of translated manual, including the interpretation of criteria assessment, may help reduce variability.

Academies and Institutes↗
PubMed2003

Log-linear models for assessing gene-age interaction and their application to case-control studies of the apolipoprotein E (apoE) gene in Alzheimer's disease.

Case-control studies provide a powerful approach for detecting disease-susceptibility genes or assessing gene-environment interactions. We investigated the situation in which the gene being studied plays a role in several diseases, and the allele frequency among subjects free of the disease of interest consequently decreases with age as subjects die from other diseases. The logistic model is one approach frequently used for analyzing case-control data, but it cannot accommodate this dependence of genotype and age. Using a log-linear model, we therefore proposed a hierarchical procedure that could be used as a valid method for assessing interactions in such situations. We then applied this procedure to observed data on Alzheimer's disease and the apolipoprotein E gene in Japan. We were able to derive an appropriate inference on whether the interaction was a gene-age interaction or merely a bias due to death from other diseases.

Age Factors↗
PubMed2003

Long-term effect of 5-fluorouracil enhanced by intermittent administration of polysaccharide K after curative resection of colon cancer. A randomized controlled trial for 7-year follow-up.

BACKGROUND AND AIMS: The efficacy of a biological response modifier polysaccharide K in adjuvant immunochemotherapy was evaluated in primary colon cancer patients with macroscopic Dukes' C after curative resection. PATIENTS AND METHODS: Employing the minimization method using three factors (lymph node metastases, preoperative serum CEA level, and institution), 446 patients were allocated into groups P and C. Group P received immunochemotherapy, oral PSK (3 g per day) followed by oral 5-FU (200 mg/body per day), while group C received only intermittent chemotherapy, oral 5-FU (200 mg per day) followed by 4-week rest. Both groups received ten courses. RESULTS: Survival for cancer death was significantly higher in group P than in group C, but there was no difference in 7-year disease-free survival or overall survival had. CONCLUSION: Repeated alternating administration with PSK followed by 5-FU can improve survival for cancer death.

Adenocarcinoma↗
PubMed2003

Randomized controlled trial comparing oral doxifluridine plus oral cyclophosphamide with doxifluridine alone in women with node-positive breast cancer after primary surgery.

PURPOSE: We compared the therapeutic usefulness of doxifluridine (5'-DFUR) alone and a combination of 5'-DFUR plus cyclophosphamide (CPM), both of which are considered effective against advanced and recurrent breast cancer, to determine which treatment is more beneficial as postoperative adjuvant chemotherapy. PATIENTS AND METHODS: A total of 1,131 women with node-positive primary breast cancer were randomly assigned after primary surgery to receive 5'-DFUR alone or 5'-DFUR plus CPM. All patients initially received 5'-DFUR in an oral dose of 1,200 mg/d for 4 weeks, starting 4 weeks after surgery. Chemotherapy was then not given for 2 weeks. Patients in the 5'-DFUR group subsequently received five 4-week cycles of treatment consisting of oral 5'-DFUR (1,200 mg/d) for the first 2 weeks and no chemotherapy for the next 2 weeks. Those assigned to the 5'-DFUR plus CPM group also received oral CPM 100 mg/d for the first 2 weeks and no chemotherapy for the next 2 weeks. Women 50 years or older concurrently received 20 mg/d of tamoxifen for 2 years in both groups. RESULTS: Of the 1,088 eligible women, 546 were assigned to receive 5'-DFUR alone and 542 were assigned to receive 5'-DFUR plus CPM. Overall disease-free survival was significantly better in women who received 5'-DFUR plus CPM than in those who received 5'-DFUR alone (log-rank test, P =.021). Toxic effects occurred in 20.0% of patients (109 of 546) in the 5'-DFUR group and 32.3% of patients (175 of 542) in the 5'-DFUR plus CPM group (chi(2) test, P <.001). CONCLUSION: Combination therapy with 5'-DFUR plus CPM is more effective in preventing recurrence than 5'-DFUR alone.

Administration, Oral↗