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ABSTRACT: Uracil-Tegafur (UFT), an oral fluorinated pyrimidine chemotherapeutic agent, has been used for adjuvant chemotherapy in curatively resected colorectal cancer patients. Past trials and meta-analyses indicate that it is somewhat effective in extending survival of patients with rectal cancer. The objective of this study was to perform a reappraisal of randomised clinical trials conducted in this field. We designed an individual patient-based meta-analysis of relevant clinical trials to examine the benefit of UFT for curatively resected rectal cancer in terms of overall survival (OS), disease-free survival (DFS), and local relapse-free survival (LRFS). We analysed individual patient data of five adjuvant therapy randomised clinical trials for rectal cancer, which met the predetermined inclusion criteria. These five trials had a combined total of 2091 patients, UFT as adjuvant chemotherapy compared to surgery-alone, 5-year follow-up, intention-to-treat-based analytic strategy, and similar endpoints (OS and DFS). In a pooled analysis, UFT had significant advantage over surgery-alone in terms of both OS (hazard ratio, 0.82; 95% confidence interval (CI), 0.70-0.97; P=0.02) and DFS (hazard ratio, 0.73; 95%CI, 0.63-0.84; P<0.0001). This individual patient-based meta-analysis demonstrated that oral UFT significantly improves both OS and DFS in patients with curatively resected rectal cancer.
British Journal of Cancer 05/2007; 96(8):1170-7. · 5.04 Impact Factor
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ABSTRACT: Oral 5-fluorouracil and its prodrugs (tegafur, carmofur) is now being studied for adjuvant chemotherapy of curatively resected colorectal cancers. To evaluate the effect of these oral fluoropyrimidines (o-FPs), an individual patient data (IPD) meta-analysis of randomized clinical trials was performed in Japan as an inter-trialist group study.
Data from the three clinical trials in which postoperative adjuvant therapy with o-FPs was compared with surgery alone in patients with colorectal cancer were sought. IPD from a total of 4960 patients with follow-up periods of at least 5 years were analyzed.
The results of the meta-analysis on an 'intention to treat' basis demonstrated a significant benefit of o-FPs in terms of the disease-free survival (DFS) of the total patients [risk ratio (RR) 0.830, 95% confidence interval (CI) 0.742-0.929, P = 0.001]. o-FPs were also demonstrated to be effective for survival in rectal cancer (RR 0.857, 95% CI 0.734-0.999, P = 0.049) and in Dukes'C colorectal cancer (RR 0.828, 95% CI 0.711-0.965, P = 0.016).
The results suggest the advantage of long term o-FPs, possibly with the injection of mitomycin C, for prognosis for curatively resected colorectal cancer patients.
Japanese Journal of Clinical Oncology 03/1999; 29(2):78-86. · 1.78 Impact Factor
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ABSTRACT: The role of the spleen in tumor immunology is still controversial in that it can either enhance or suppress the antitumor immune response depending on the tumor-bearing host. To clarify this biphasic effect of the spleen, a clinical evaluation of splenectomy in conjunction with immunotherapy and the host immune status was performed in gastric cancer patients. The effect of splenectomy and immunotherapy in 253 gastric cancer patients enrolled in a prospective randomized trial (SIP) was analyzed using the Cox's proportional hazards model in terms of the covariate interaction of the preoperative immunosuppressive acidic protein (IAP) level. In patients with high IAP levels (>580 microg/ml) with predicted negative antitumor immune reactions, splenectomy improved the prognosis. In patients with lower IAP values, conversely, the preservation of the spleen and immunotherapy demonstrated a significant benefit to survival. The spleen was shown to have a biphasic activity in terms of its antitumor immune response depending on the IAP level of the patient. The effect of immunotherapy is significantly influenced by the activity of spleen cells. The preoperative IAP level is therefore considered to be a possible indicator for the effectiveness of splenectomy and immunotherapy in curatively resected gastric cancer patients.
Surgery Today 02/1999; 29(6):504-10. · 1.22 Impact Factor
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ABSTRACT: In a previous randomized clinical trial against curatively resected gastric cancer, we compared the effect of immunochemotherapy to chemotherapy and obtained significantly better survival and disease-free survival time (DFS) in a combined therapy group. Although DFS was analysed with a conventional approach in which the onset of relapse was defined as the diagnosis of relapse, we considered it necessary to re-analyse the data and compare the results of an interval-censored approach with the conventional approach, in order to examine whether the conclusion might be altered depending on the approach.
Japanese Journal of Clinical Oncology 01/1998; 27(6):445-6. · 1.78 Impact Factor
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J Sakamoto,
H Nakazato,
S Teramukai, Y Ohashi,
Y Takahashi,
M Mai,
T Toge,
H Okura,
S Kodaira,
S Maetani,
K Okajima,
K Nomoto,
T Hattori,
K Inokuchi
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ABSTRACT: A large-scale retrospective study was undertaken to evaluate the association between preoperative plasma carcinoembryonic antigen (CEA) levels and the prognosis of 2768 gastric cancer patients who underwent curative gastrectomy between 1983 and 1984 at 66 leading medical institutions in Japan Postoperative follow-up was at least 5 years. Preoperative plasma CEA levels were also analysed against other prognostic factors. Preoperative plasma CEA levels showed strong correlations to the degree of lymph node metastasis (P < 0.001), TNM stage (P = 0.004) and the histopathology of the gastric cancer (P < 0.001). Preoperative CEA levels were also evaluated against survival, after being adjusted for the effect of clinically important factors by multivariate analysis. Patients with lower preoperative plasma CEA levels survived significantly longer than patients with higher CEA levels (P = 0.0001). This analysis demonstrates that curatively resected gastric cancer patients with higher preoperative plasma CEA levels have a poorer prognosis than those with lower levels, despite the adjustment for the effects of major prognostic factors.
Surgical Oncology 07/1996; 5(3):133-9. · 2.44 Impact Factor
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ABSTRACT: Immunosuppressive acidic protein (IAP) has been reported to have close correlation with the impairment of host immune response. To evaluate the significance of IAP in clinical studies, the prognostic value of preoperative IAP was investigated in clinical trials of patients with gastric carcinoma after curative resection.
An appropriate IAP threshold value of 580 micrograms/mL was determined using Cox's proportional hazards model. Five-year survival rates were estimated for high and low IAP groups in three different clinical studies. Meta-analysis was performed based on individual patient data, and summarized hazard ratios were estimated using a stratified proportional hazards model.
Meta-analysis of the three clinical trials demonstrated that patients with preoperative IAP levels above the threshold had significantly poorer cancer related survival (P = 0.0039) and absolute survival (P = 0.0023), even after adjustment for the major prognostic factors.
Gastric carcinoma patients with an IAP value above the threshold level of 580 micrograms/mL have a higher risk of cancer death and absolute death than patients with an IAP value below the threshold value.
Cancer 07/1996; 77(11):2206-12. · 4.77 Impact Factor
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ABSTRACT: Comparisons of surgical procedures and the identification of prognostic factors in pancreatic cancer were carried out on 158 patients who underwent surgery in Aichi Cancer Center from 1975 to 1991 for advanced pancreatic ductal adenocarcinoma. Survival and 'hospital-free survival (HFS), which we consider the best general means of measuring quality of life (QOL) in such severe and often fatal disease, were identified as primary end points, and the effect of pancreatectomy, compared with palliative surgery (by-pass operation, etc.) for TNM Stages III and IV pancreatic cancer was evaluated. Both survival and HFS were significantly longer in the group of patients who underwent pancreatectomies (R group, n 25) compared to the group without pancreatic resection (NR group, n 35) in Stage III cases. In Stage IV cases, however, no significant difference was observed between the R (n 12) and NR (n 86) groups. From these results, we conclude that an extensive pancreatic resection against Stage III pancreatic cancer may improve prognosis. For Stage IV pancreatic cancers, however, aggressive surgery might not always be beneficial either for survival or for QOL.
Japanese Journal of Clinical Oncology 05/1995; 25(2):37-45. · 1.78 Impact Factor
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ABSTRACT: Preoperative serum levels of carcinoembryonic antigen (CEA) and/or carbohydrate antigen 19.9 (CA19.9) were measured in 90 patients with advanced pancreatic cancer. CEA antigen was above the cutoff levels of 5.0 ng/ml in 51% of patients and CA19.9 was above the cutoff limit of 37 U/ml in 87% of patients. High preoperative CEA and CA19.9 levels were related to a poor prognosis of the patients. In multivariate analysis, the hazard rate was significantly higher in the high-CEA group (> 2.5 ng/ml) compared to the low-CEA group (< 2.4 ng/ml). An increase in CEA and/or CA19.9 within 1 month after the operation was also significantly related to the hazard rate. This study reconfirms the prognostic importance of preoperative and postoperative CEA and CA19.9.
Pancreas 12/1994; 9(6):735-40. · 2.39 Impact Factor
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ABSTRACT: The prognostic value of immunosuppressive acidic protein (IAP), which is known to suppress various immune responses in cancer patients, was studied in a prospective randomized trial of advanced gastric cancer patients, designed to evaluate the effect of PSK, a kind of biological response modifier with protein-bound polysaccharides. Preoperative serum IAP levels were determined in 228 patients who received radical gastric resection and tests conducted in one laboratory by the single radial immunodiffusion (SRID) method. All patients were followed up for 24 months or more. There was an overall significant difference in disease-free survival time in favour of the PSK-treated group compared with the control group. Preoperative IAP values were strongly associated with disease-free survival time. The statistical analysis to define an appropriate cut-off level for IAP was performed using Cox's proportional hazards model. The most significant difference was observed at the threshold value of 580 micrograms/ml, the hazard ratio being 2.13 with a 95% confidence interval [1.17, 3.88] (P = 0.013). Patients in the PSK-treated group with a preoperative IAP of lower than 580 micrograms/ml showed improved disease-free survival (P = 0.029), however, no significant difference was seen between the two groups when the preoperative IAP exceeded the threshold level. From these results, 580 micrograms/ml is postulated to be the most appropriate threshold value for predicting the prognosis of advanced gastric cancer patients, and it is suggested that PSK would be most effective in patients whose preoperative IAP level is lower than the threshold level.
Surgery Today 02/1992; 22(6):530-6. · 1.22 Impact Factor
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ABSTRACT: One of the objectives of randomization is to balance the number of patients in each level and combination of levels of prognostic factors. However, as the number of possible prognostic factors increases, some imbalance may occur and make the results of the analysis less interpretable. In order to balance the marginal distribution of each factor and to facilitate more interpretable trial results, the "minimization method" reported by Pocock was applied in our multi-center immunochemotherapy clinical trial. Balancing in every institution was achieved by using Zelen's prespecified value d = 3 for replacing provisional assignment in the individual institution. Nonmetric principal component analysis in S, N factors which were used in minimization process showed good equilibration between groups. Also, in uncontrolled background factors, such as cancer pathology or Borrmann types, acceptable balance was obtained spontaneously at the end of the trial.
Gan to kagaku ryoho. Cancer & chemotherapy 07/1988; 15(6):1935-42.
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ABSTRACT: The benefits of immunochemotherapy with a penicillin-treated, lyophilized preparation of Streptococcus pyogenes, OK-432 (Picibanil), were reassessed in patients with resected non-small-cell lung cancer through a meta-analysis based on data from 1,520 patients enrolled in 11 randomized clinical trials. All 11 trials were started before 1991, and the subjects had been followed up for at least 5 years after surgery and randomization. In these trials, standard chemotherapy was compared with the same therapy plus OK-432. The endpoint of interest was overall survival, and analysis was based on intent-to-treat population without patient exclusion. Data were analyzed using the Mantel-Haenszel method. The 5-year survival rate for all eligible patients in the 11 trials was 51.2% in the immunochemotherapy group versus 43.7% in the chemotherapy group. The odds ratio (OR) for overall survival was 0.70 (95% CI = 0.56-0.87, p = 0.0010). Analysis of four trials in which central randomization was performed also reconfirmed a significantly longer survival time for the immunochemotherapy group (OR = 0.66, 95% CI = 0.44-1.00, p = 0.049). Based on these results of meta-analysis, it is postulated that postoperative adjuvant immunochemotherapy using OK-432 might improve the survival of patients after resection of non-small-cell lung cancer.
Journla of Immunotherapy 24(3):250-6. · 3.27 Impact Factor
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ABSTRACT: To reappraise the benefits of the long supported chemotherapy with carmofur, a meta-analysis based on individual patient data from the three clinical trials was performed by pooling 614 patients from three trials, there is a statistically significant survival benefit (2p=0.032) and disease-free survival (DFS) benefit (2p=0.021) for carmofur; and a highly significant advantage for carmofur in DFS (2p=0.0004) and in survival (2p=0.004) in Dukes' C patients. This IPD meta-analysis strongly suggested an effect of oral carmofur in a long supported chemotherapy for curatively resected colorectal carcinoma.
Oncology Reports 8(3):697-703. · 1.84 Impact Factor
