Biomedical subjects

Nagio Takigawa

Publications and source records attributed to Nagio Takigawa.

12 recordsLinked to original sources

PubMed2003

Phase I/II study of altered schedule of cisplatin and etoposide administration and concurrent accelerated hyperfractionated thoracic radiotherapy for limited-stage small-cell lung cancer.

To improve the efficacy of a combination of cisplatin and etoposide and concurrent accelerated twice-daily thoracic radiotherapy against limited-stage small-cell lung cancer, we conducted a phase I/II study using an altered schedule of chemotherapy administration. Chemotherapy consisted of four cycles of cisplatin (days 1 and 8) and etoposide (days 1, 2, 8, and 9) every 4 weeks. Accelerated hyperfractionated thoracic radiation (1.5 Gy twice daily x 30 fractions, total dose of 45 Gy) was concurrently given with the first cycle of chemotherapy. The recommended doses of cisplatin and etoposide determined in the phase I study were 40 and 80 mg/m(2), respectively. In the phase II study, the overall response rate was 100% (complete response: 32%, partial response: 68%). By a median follow-up time of 29 months, median radiation-outfield progression-free survival was 13.4 months, while radiation-infield progression-free survival did not reach median value. The median overall survival time was 22.9 months, with survival rate of 48.4% at 2 years. Major toxicities were leukopenia and neutropenia (>/=grade 3, 92% each). The local control and overall survival demonstrated in this study were excellent. However, the insufficient distant control suggests a need for development of more active chemotherapy regimens.

Aged↗

PubMed2002

Parathyroid hormone-related protein measured at the time of first visit is an indicator of bone metastases and survival in lung carcinoma patients with hypercalcemia.

BACKGROUND: Parathyroid hormone-related protein (PTH-rP) is a major cause of tumor-induced hypercalcemia (TIH) and frequently is found to be elevated in serum of patients with TIH. In the current study, the authors examined the usefulness of PTH-rP measurement at the time of first presentation in the follow-up of lung carcinoma patients with TIH. METHODS: The authors retrospectively studied 23 of 1149 lung carcinoma patients who were found to have TIH at the time of first presentation for the correlation between serum PTH-rP and the development of bone metastases and survival compared with lung carcinoma patients without TIH who were matched by gender, age, Eastern Cooperative Oncology Group performance status, histological type of tumor, and stage of the disease. RESULTS: Twenty-three lung carcinoma patients with TIH demonstrated significantly increased serum levels of PTH-rP (mean +/- standard error [SE], 84.1 +/- 16.5 pmol/L) compared with control patients without TIH (mean +/- SE, 36.2 +/- 2.0 pmol/L) at the time of first presentation, (P < 0.001). In these hypercalcemic patients, patients whose serum PTH-rP was > 150 pmol/L (n = 16) were found to have a significantly increased rate of bone metastases (71.4% vs. 12.5%; P = 0.01) and decreased survival (median survival of 1.4 months vs. 5.4 months; P < 0.015) compared with patients whose serum PTH-rP was < 150 pmol/L (n = 7). CONCLUSIONS: The data from the current study suggest that serum PTH-rP as determined at the time of first presentation is a useful indicator of not only hypercalcemia but also bone metastasis and eventual survival in patients with lung carcinoma.

Adult↗

PubMed2002

Interleukin-12 augments cytolytic activity of peripheral blood mononuclear cells against autologous lung cancer cells in combination with IL-2.

The majority of patients with advanced lung cancer die within a few years. Accordingly, new therapeutic modalities need to be developed. Interleukin (IL)-12 was previously known as natural killer (NK) cell stimulatory factor or cytotoxic lymphocyte maturation factor. By virtue of its effects on T cells and NK cells, IL-12 seems to be one of the key cytokines that regulates cell-mediated anti tumor immune responses. Recently, there has been a substantial interest in the potential applications of IL-12 in the treatment of lung cancer. However, there have been no reports about the effect of IL-12 on peripheral blood mononuclear cells (PBMCs) obtained from lung cancer patients in an autologous setting. In this study, we examined the cytotoxicity of PBMC activated by IL-2, IL-12 or both against K562 or autologous lung cancer cells. In contrast to the effect of IL-2 on NK activity, IL-12 alone augmented NK activity against K562 cells, but not against autologous lung cancer cells. IL-12 augmented the IL-2 mediated cytotoxicity of PBMC against both K562 and autologous lung cancer cells. In the absence of IL-2, IL-12 alone cannot induce an autologous anti-tumor effect in vivo. In summary, our results clearly demonstrated that IL-12 can augment the cytolytic activity of PBMC against K562 and autologous lung cancer cells when combined with IL-2, although, IL-12 alone was unable to induce a marked increase in the cytotoxicity against autologous lung cancer cells. These results suggest that an administration of IL-12 in combination with IL-2 may be a useful therapeutic option for solid tumors.

Aged↗

PubMed2002

A phase III randomized trial comparing vindesine and cisplatin with or without ifosfamide in patients with advanced non-small-cell lung cancer: long-term follow-up results and analysis of prognostic factors.

UNLABELLED: In order to evaluate the activity and toxicity of a three-drug combination of vindesine, ifosfamide and cisplatin (VIP) for inoperable non-small-cell lung cancer (NSCLC), we conducted a randomized trial comparing VIP with a two-drug combination of cisplatin and vindesine (VP). Between September 1987 and March 1992, a total of 132 patients with stage III or IV NSCLC were randomly allocated to either VIP or VP. The VIP regimen consisted of vindesine (VDS 3 mg/m(2) on days 1 and 8), ifosfamide (IFX 1300 mg/m(2) on days 1-5), and cisplatin (CDDP 20 mg/m(2) on days 1-5). The VP regimen consisted of VDS and CDDP with the same dose and schedule as the VIP regimen. Both regimens were repeated every 4 weeks. Objective response rates were 49.3% (95% confidence interval: 95%CI, 43.1-55.4%) in the VIP arm and 44.6% (95%CI, 38.4-50.2%) in the VP arm; the difference was not significant (P=0.5390). Median response duration, median survival time, and two-year survival rates were 26.5 weeks, 49.6 weeks, and 14.9% in the VIP arm and 28.7 weeks, 37.1 weeks, and 12.3% in the VP arm, respectively. There were also no significant differences between these two treatment arms. In comparison with the VP regimen, however, a survival advantage of the VIP regimen could be confirmed when the data were evaluated with Cox's multivariate analysis (P=0.0131). In both arms, the principal toxicity was myelosuppression, which was significantly more frequent in the VIP arm, although generally well tolerated. CONCLUSION: This study suggested the survival advantage of the VIP regimen over the VP regimen for treatment of patients with advanced NSCLC.

Adult↗

PubMed2002

Daily low-dose cisplatin and concurrent thoracic irradiation for poor-risk patients with unresectable non-small-cell lung cancer.

A pilot study was conducted to assess the efficacy and feasibility of daily low-dose cisplatin with concurrent thoracic irradiation for clinically unresectable non-small-cell lung cancer (NSCLC). Patients with inoperable NSCLC who had poor risk factors such as advanced age, poor performance status, poor lung function, or concomitant active malignancy were entered into the study. Low-dose cisplatin (6 mg/m2) was administered daily before concurrent thoracic irradiation (2 Gy/day; total dose of 60 Gy) was given. Twenty-five patients were registered. The majority of the patients had either stage IIIA (24.0%) or stage IIIB (60.0%) disease. Fifteen patients (60.0%) completed the planned treatment. Both chemotherapy and radiotherapy were stopped in 3 patients (12.0%) due to poor response, and 7 patients (28.0%) partly received radiotherapy alone as a result of their toxicity response. The proportion of total administered dose to planned dose was 90.9% for chemotherapy and 99.3% for radiotherapy, which were comparable to those in previous studies for LA-NSCLC patients without poor risk factors. Grade 3 leukopenia and neutropenia developed in 14 patients (56.0%) and 10 patients (40.0%), respectively, but grade 4 toxicity was not encountered. Grade 3 pneumonitis and esophagitis were observed in 4 patients (16.0%) and 2 patients (8.0%), respectively. The overall response rate was 60.0%. The median survival time was 22 months, and the 2-year survival rate was 50.3%. Daily low-dose cisplatin and concurrent thoracic irradiation were well tolerated even by poor-risk patients with NSCLC, and showed a therapeutic efficacy similar to that for good-risk patients.

Adenocarcinoma↗

PubMed2002

Comparison of chemosensitivity tests: clonogenic assay versus MTT assay.

When the development of chemotherapeutic agents reaches the clinical trial stage, it is necessary to perform drug sensitivity tests quickly in order to select the most promising agents for the treatment of cancer. In order to assess the possibility of using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay as a substitute for the human tumor clonogenic assay (HTCA), we evaluated the correlation between the results obtained by these 2 assays in 5 human lung cancer cell lines. The correlation coefficient between the results of the HTCA and the MTT assay was 0.673, indicating a relatively good correlation. The correlation was most prominent in platinum analogues (r = 0.939) and good in anthracyclines/anthracenedione (r = 0.611). However, no significant correlation was observed in vinca alkaloids, etoposide, irinotecan, SN-38 (an active metabolite of irinotecan), and rhizoxin. The results of the MTT assay showed a high degree of correlation with those of the HTCA in predicting the sensitivity of cancer cell lines to platinum analogues, and anthracyclines/anthracenedione. These results suggest that the MTT assay may be more convenient and quickly performed than the HTCA and can replace HTCA in evaluating the effects of anticancer agents, especially the platinum analogues and anthracyclines/anthracenedione.

Antineoplastic Agents↗

PubMed2002

Inhibition of NF-kappaB and proteasome activity in tumors: can we improve the therapeutic potential of topoisomerase I and topoisomerase II poisons.

Activation of signaling pathways following DNA damage induced by topoisomerase (topo) poisons can lead to cell death by apoptosis. NF-kappaB, a major regulator of the stress response and a negative regulator of apoptosis is often activated following treatment with topoisomerase poisons. Since activation of NF-kappaB is generally considered to relay an anti-apoptotic signal, inactivation of this signaling molecule is considered to represent an important strategy to improve therapeutic efficacy. Although this strategy seems to be effective in some model systems, our results in human non-small cell lung cancers differed. In this review we will discuss the role of NF-kappaB in mediating topoisomerase poison-induced DNA damage and apoptosis and the consequence of inhibiting its activity. Newer insights about the importance of proteasome inhibitors and anti-apoptotic genes in topoisomerase poison-induced signaling mechanisms leading to apoptosis will also be reviewed. The knowledge obtained from these studies may be useful for translation to a clinical setting for development of more effective therapeutic strategies.

Animals↗

PubMed2002

[Docetaxel].

Explore the source record for details and available documents.

Antineoplastic Agents, Phytogenic↗

PubMedDate not supplied

Gingival metastasis in lung cancer.

Gingival metastasis is an extremely rare manifestation of lung cancer, and exhibits rapid growth with various clinical symptoms. Physicians must appropriately manage patients with lung cancer who develop gingival metastasis. Clinical records of patients with lung cancer treated at the Department of Internal Medicine II, Okayama University Hospital, between 1976 and 1998 were retrospectively reviewed. The medical literature was searched by Medline to identify reports of gingival metastasis from lung cancer. Three of 729 (0.41%) lung cancer patients developed gingival metastasis in our hospital between 1976 and 1998, and 9 additional cases of this type of metastasis were found in the literature. All were male, and median age was 57.5 years (range, 47 to 70). There were no clear correlations between development of gingival metastasis and either histologic type or location of the primary lesion. Chemotherapy or radiotherapy was effective for treatment of gingival metastasis, and the quality of life was improved. However, survival after development of gingival metastasis was very short, with median survival of only 4 months.

Aged↗

PubMedDate not supplied

Gastric perforation due to metastasis from adenocarcinoma of the lung.

We report a rare case of the development of gastric perforation at the site of metastasis from adenocarcinoma of the lung during systemic chemotherapy. We speculated that the chemotherapy-induced necrosis of the metastatic tumor might have led to the gastric perforation. To the best of our knowledge, this is the first case of chemotherapy-induced gastric perforation as a complication of lung cancer treatment.

Adenocarcinoma↗

PubMedDate not supplied

Fractionated administration of irinotecan and cisplatin for treatment of extensive-disease small-cell lung cancer: a phase II study.

BACKGROUND: A combination of irinotecan (CPT-11) and cisplatin (CDDP) was shown to be effective for extensive-disease small-cell lung cancer (ED-SCLC). To take maximum advantage of the synergistic effect between CPT-11 and CDDP, we designed a fractionated administration schedule. PATIENTS AND METHODS: Between August 1995 and September 1998, 15 previously untreated patients with ED-SCLC were enrolled. Both CPT-11 at a dose of 50 mg/m2 and CDDP at a dose of 60 mg/m2 were given on days 1 and 8, and repeated every 4 weeks up to four cycles. RESULTS: Fifteen patients were assessed for response and survival, and fourteen for toxicity. Although twelve patients (80.0%; 95% confidence interval, 51.9-95.7) achieved an objective response, complete response (CR) was not obtained. The median survival time and the actual 1-year survival rate were 9.4 months and 40.0%, respectively. Grade 3 or 4 leukopenia, neutropenia and diarrhea occurred in 71.4%, 100% and 14.3% of the patients, respectively. Enrollment into this study was stopped because CR, which was the primary endpoint, was not obtained in the consecutive 15 patients and the survival appeared to be inferior to the previous multi-institutional study (Kudoh et al, Clin Oncol 16: 1068-1074, 1998). The projected dose intensity in the present study was lower in CPT-11 and higher in CDDP compared to that in the previous report. CONCLUSION: These results suggest that the dose intensity of CPT-11 may have a major role on the activity of SCLC in this combination.

Adult↗

PubMedDate not supplied

Prognostic significance of mutant p53 protein, P-glycoprotein and glutathione S-transferase-pi in patients with unresectable non-small cell lung cancer.

BACKGROUND: The prognostic significance of mutant p53 protein, p-glycoprotein (P-gp) and glutathione S-transferase-pi (GST-pi) in patients with unresectable non-small cell lung cancer (NSCLC) has not been established. MATERIALS AND METHODS: We performed immunohistochemical staining of p53, P-gp and GST-pi using transbronchial biopsy specimens obtained from previously untreated NSCLC patients. RESULTS: Of 45 patients examined, p53 immunostaining was positive in 18 (40%) patients. The objective response rate by cisplatin (CDDP)-based chemotherapy was significantly lower in patients with p53-positive tumors compared to those with p53-negative tumors (22% versus 59%, p = 0.0143). Survival of the patients with p53-positive tumors was significantly shorter than those with p53-negative tumors (median survival time: 4.6 months versus 12.2 months, p = 0.011), which was confirmed by the multivariate analysis (p = 0.0243). However, P-gp and GST-pi showed no significant relationship with either response rate or survival in patients with unresectable NSCLC receiving CDDP-based chemotherapy. CONCLUSION: p53 alteration is an independent and significant indicator to predict unfavorable prognosis in patients with unresectable NSCLC.

ATP Binding Cassette Transporter, Subfamily B↗