[show abstract][hide abstract] ABSTRACT: Cisplatin is used to treat lung cancer; however, it is also a known carcinogen. Cyclooxygenase-2 (COX-2) inhibitors have been shown to prevent carcinogen-induced experimental tumors. We investigated the effect of a COX-2 inhibitor, celecoxib, on cisplatin-induced lung tumors. One hundred twenty 4-week-old A/J mice were divided into 6 groups: group 1, no treatment; group 2, low-dose celecoxib (150 mg/kg); group 3, high-dose celecoxib (1,500 mg/kg); group 4, cisplatin alone; group 5, cisplatin plus low-dose celecoxib;and group 6, cisplatin plus high-dose celecoxib. Mice in groups 4-6 were administered cisplatin (1.62 mg/kg, i.p.) once a week for 10 weeks between 7 and 16 weeks of age. All mice were sacrificed at week 30. Tumor incidence was 15.8% in group 1, 25% in group 2, 26.3% in group 3, 60% in group 4, 50% in group 5, and 50% in group 6. Tumor multiplicity was 0.2, 0.3, 0.3, 1.3, 1.0, and 0.6 in groups 1-6, respectively. Tumor multiplicity in the cisplatin-treated mice was reduced by celecoxib treatment in a dose-dependent manner (p < 0.05, group 4 vs. group 6). Celecoxib significantly reduced COX-2 expression in cisplatin-induced tumors (p < 0.01, group 4 vs. group 6).
[show abstract][hide abstract] ABSTRACT: The objective of this study was to evaluate the utility of the determination of adenosine deaminase (ADA) level in pleural fluid for the differential diagnosis between tuberculous pleural effusion (TPE) and malignant pleural effusion (MPE) in Japan, a country with intermediate incidence of tuberculosis (TB). We retrospectively reviewed the clinical records of 435 patients with pleural effusion and investigated their pleural ADA levels as determined by an auto analyzer. ROC analysis was also performed. The study included patients with MPE (n＝188), TPE (n＝124), benign nontuberculous pleural effusion (n＝94), and pleural effusion of unknown etiology (n＝29). The median ADA level in the TPE group was 70.8U/L, which was significantly higher than that in any other groups (p＜0.05). The area under the curve (AUC) in ROC analysis was 0.895. With a cut-off level for ADA of 36U/L, the sensitivity, specificity, positive predictive value, and negative predictive value were 85.5%, 86.5%, 69.7%, and 93.6%, respectively. As many as 9% of patients with lung cancer and 15% of those with mesothelioma were false-positive with this ADA cutoff setting. Although the ADA activity in pleural fluid can help in the diagnosis of TPE, it should be noted that some cases of lung cancer or mesothelioma show high ADA activity in geographical regions with intermediate incidence of TB, in contrast to high prevalence areas.
[show abstract][hide abstract] ABSTRACT: Chemotherapy is a mainstay in the treatment of extensive-disease small-cell lung cancer (ED-SCLC), although the survival benefit remains modest. We conducted a phase II trial of amrubicin (a topoisomerase II inhibitor) and topotecan (a topoisomerase I inhibitor) in chemotherapy-naïve and relapsed SCLC patients.
Amrubicin (35 mg/m(2)) and topotecan (0.75 mg/m(2)) were administered on days 3-5 and 1-5, respectively. The objective response rate (ORR) was set as the primary endpoint, which was assessed separately in chemotherapy-naïve and relapsed cases.
Fifty-nine patients were enrolled (chemotherapy-naïve 31, relapsed 28). The ORRs were 74% and 43% in the chemotherapy-naïve and relapsed cases, respectively. Survival data were also promising, with a median progression-free survival time and median survival time of 5.3 and 14.9 months and 4.7 and 10.2 months in the chemotherapy-naïve and relapsed cases, respectively. Even refractory-relapsed cases responded to the treatment favorably (27% ORR). The primary toxicity was myelosuppression with grades 3 or 4 neutropenia in 97% of the patients, which led to grades 3 or 4 febrile neutropenia in 41% of the patients and two toxic deaths.
This phase II study showed the favorable efficacy and moderate safety profiles of a topotecan and amrubicin two-drug combination especially in relapsed patients with ED-SCLC.
Lung cancer (Amsterdam, Netherlands) 02/2011; 74(1):80-4. · 3.14 Impact Factor
[show abstract][hide abstract] ABSTRACT: The relationship between poor performance status (PS) and toxicity during chemotherapy is controversial. We examined this for erlotinib monotherapy in non-small cell lung cancer (NSCLC) patients.
Toxicity during the first month of therapy was recorded in 209 patients receiving erlotinib for NSCLC, and its association with PS was assessed.
Of 209 patients, 52, 115, 30 and 12 had a PS of 0, 1, 2 and 3-4, respectively. Treatment was discontinued in 26% of patients within 1 month, with a higher rate in poorer PS patients (17%, 25%, 37% and 42%). Discontinuation was predominantly due to disease progression, rather than adverse events, in both the whole cohort (82% vs. 18%) and the poorest PS subgroup (100% vs. 0%). Three, two, and four patients with a PS of 1, 2 and 3-4, respectively, died within 1 month; all six deaths of PS 2-4 patients were attributed to disease progression. Treatment interruption and dose reduction rates were similar among the subgroups. The principal adverse event was skin rash, with identical incidence in all PS subgroups.
Poor PS is unlikely to increase the risk for toxicity during erlotinib monotherapy, but was related to low compliance, probably because of disease progression rather than treatment-related toxicity.
Lung cancer (Amsterdam, Netherlands) 12/2010; 70(3):308-12. · 3.14 Impact Factor
[show abstract][hide abstract] ABSTRACT: Gefitinib is an epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI). N-Nitrosamine-4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), a potent carcinogen found in tobacco smoke, induces lung tumors in A/J mice. NNK induces cellular transformation resulting in the over-expression of EGFR. Accordingly, EGFR may be a target for cancer prevention. In this study, we investigated the effect of gefitinib on NNK-induced tumorigenesis and the carcinogenicity of gefitinib in A/J mice. A total of 180 four-week-old female A/J mice were randomly divided into six groups: group 1 (controls), treated with deionized water; group 2, treated with 5 mg/kg p.o. gefitinib; group 3, treated with 50 mg/kg p.o. gefitinib (to test the carcinogenicity of gefitinib); group 4 (controls for NNK treatment), treated with deionized water; group 5, treated with 5 mg/kg p.o. gefitinib; and group 6, treated with 50 mg/kg p.o. gefitinib and injected with NNK once at 8 weeks of age to test the chemopreventive activity of gefitinib. Gefitinib was given once a day, 5 days a week by gavage, beginning at 4 weeks of age and continuing for 26 weeks. All mice were sacrificed at 30 weeks of age. The multiplicities of the NNK-induced lung tumors were significantly suppressed in a dose-dependent manner. Gefitinib had no effect on body weight at a low dose. The administration of gefitinib alone for 26 weeks did not induce tumorigenesis; instead, it significantly suppressed the incidence of spontaneous tumors in the mice, in contrast with other anti-cancer agents. Gefitinib did not induce lung fibrosis when compared with control mice by Azan-Mallory staining. Our results suggest that gefitinib has a weak but significant chemopreventive effect with no carcinogenicity or pulmonary toxicity in A/J mice.
Lung cancer (Amsterdam, Netherlands) 02/2009; 65(3):284-9. · 3.14 Impact Factor
[show abstract][hide abstract] ABSTRACT: A combination of S-1, a newly developed oral 5-fluorouracil derivative, and cisplatin is reported to show anti-tumour activity against advanced non-small cell lung cancer (NSCLC). Because S-1 shows synergistic effects with radiation, we conducted a phase I study to evaluate the maximum tolerated doses (MTDs), recommended doses (RDs), and dose-limiting toxicities (DLTs) of cisplatin and S-1 when combined with concurrent thoracic radiation (total dose of 60 Gy with 2 Gy per daily fraction) in patients with locally advanced NSCLC. Chemotherapy consisted of two 4-week cycles of cisplatin administered on days 1 and 8, and S-1 administered on days 1-14. S-1/cisplatin dosages (mg/m(2)/day) were escalated as follows: 60/30, 60/40, 70/40, 80/40 and 80/50. Twenty-two previously untreated patients were enrolled. The MTDs and RDs for S-1/cisplatin were 80/50 and 80/40, respectively. DLTs included febrile neutropaenia, thrombocytopaenia, bacterial pneumonia and delayed second cycle of chemotherapy. No patient experienced radiation pneumonitis>grade 2 and only one patient experienced grade 3 radiation oesophagitis. The overall response rate was 86.4% with a median survival time of 24.4 months. These results indicate that combination cisplatin-S-1 chemotherapy with concurrent thoracic radiation would be a feasible treatment option and a phase II study is currently under way.
Lung cancer (Amsterdam, Netherlands) 01/2009; 65(1):74-9. · 3.14 Impact Factor
[show abstract][hide abstract] ABSTRACT: We conducted a phase I/II study of triplet chemotherapy consisting of cisplatin (CDDP), docetaxel (DCT) and gemcitabine (GEM) in patients with advanced non-small-cell lung cancer (NSCLC).
Fifty-three untreated patients with stage IIIB or IV NSCLC were enrolled. All drugs were given on days 1 and 8. The doses of CDDP and DCT were fixed at 40 mg/m(2) and 30 mg/m(2), respectively. In the phase I portion, a dose escalation study of GEM with starting dose of 400 mg/m(2) was conducted and primary objective in the phase II portion was response rate.
The maximally tolerated dose (MTD) and recommended dose (RD) of GEM were determined as 800 mg/m(2) because grade 3 non-hematological toxicity (liver damage, diarrhea, and fatigue) developed in three of nine patients evaluated at that dose level. In pharmacokinetic analysis, C (max) and AUC of dFdC and dFdU were increased along with the dose escalation of GEM. However, no relationship between pharmacokinetic parameters and toxicity or response was observed. Objective response rate was 34% and median survival time was 11.7 months. Though major toxicity was myelosuppression, there were no life-threatening toxicities.
These results indicate that this triplet chemotherapy is feasible and effective in patients with advanced NSCLC.
Cancer Chemotherapy and Pharmacology 07/2007; 60(1):53-9. · 2.80 Impact Factor
[show abstract][hide abstract] ABSTRACT: We describe a 55-year-old man with advanced adenocarcinoma of the lung who received gefitinib ('IRESSA'). After gefitinib administration for 7 months, computed tomography scan of the chest demonstrated diffuse ground glass opacity and he was suspected to have developed gefitinib-induced interstitial lung disease (ILD). However, transbronchial lung biopsy (TBLB) revealed tumor cells in the middle-size lung vessels. Afterwards, multiple infarctions of the brain, spleen and left kidney were detected. Then, he was considered to have developed systemic tumor emboli, a rare complication. The clinical presentation of this patient was difficult to discriminate from that of ILD, and TBLB was useful in the differential diagnosis.
Internal Medicine 10/2005; 44(9):979-82. · 0.97 Impact Factor
[show abstract][hide abstract] ABSTRACT: To evaluate the usefulness and pharmacokinetics of docetaxel in the treatment of elderly patients with advanced non-small-cell lung cancer.
Chemotherapy-naive elderly patients (aged at least 76 years) with locally advanced or metastatic non-small-cell lung cancer were accrued. Eligible patients received at least two cycles of docetaxel at a dose of 60 mg/m2 on day 1 over 1 h every 3 weeks. Patients who were considered ineligible for this study were also registered. Symptom control was assessed using a questionnaire during the treatment period. The pharmacokinetics of docetaxel were evaluated in the first cycle of chemotherapy.
Of 35 elderly patients, 15 (43%) met the study eligibility criteria. The reasons for ineligibility consisted mainly of poor performance status, poor bone marrow function, and hypoxemia (six patients each). A total of 49 cycles of chemotherapy (median 2 cycles, range 1-12 cycles) were administered to the eligible patients, six of whom achieved a partial response (overall response rate 40%, 95% confidence interval 15-65%). The major toxicity was hematologic, with grade 3 or greater neutropenia and grade 3 neutropenic fever developing in 13 patients (87%) and five patients (33%), respectively. Symptoms, as assessed in terms of the symptom control score, did not clearly decline during the treatment period. The values (mean+/-SD) of Cmax, AUC(0-->inf), and t(1/2) were 1.35+/-0.32 microg/ml, 1.79+/-0.52 microg h/ml, and 4.1+/-2.3 h, respectively.
Although the validity of the results of this study is limited due to the small sample size, docetaxel appears effective in selected elderly patients with advanced non-small-cell lung cancer.
Cancer Chemotherapy and Pharmacology 10/2004; 54(3):230-6. · 2.80 Impact Factor
[show abstract][hide abstract] ABSTRACT: We describe a patient with adenocarcinoma of the lung who developed hydronephrosis secondary to compression by right common iliac lymph node metastases. The most common primary sites of cancers causing ureteral obstruction are the cervix, prostate, bladder and colo-rectum. To date, few reports of ureteral obstruction attributable to lung cancer have been published. Although rare, physicians should be aware that hydronephrosis can complicate the course of patients with non-small cell lung cancer.
Anticancer research 01/2003; 23(3C):2915-6. · 1.71 Impact Factor
[show abstract][hide abstract] ABSTRACT: Atypical adenomatous hyperplasia (AAH) has been reported to be a precancerous lesion of pulmonary adenocarcinoma. Cyclooxygenase-2 (COX-2), Fas and Fas ligand (FasL) are believed to be involved in the pathogenesis and progression of cancer.
We examined the expression of COX-2, Fas and FasL in 31 tissue specimens of adenocarcinoma and 9 of AAH using an immunohistochemical method.
COX-2 staining was observed in 20 (65%) specimens of adenocarcinoma and 2 (22%) of AAH. There was a significant difference in incidence of expression between these two groups (p = 0.025). All tumor specimens obtained from three patients with simultaneous multiple adenocarcinoma showed positive COX-2 staining. In two patients having both adenocarcinoma and AAH, COX-2 expression was detected in adenocarcinoma but not in AAH. Fas was expressed in 5 (16%) adenocarcinoma and 2 (22%) AAH specimens. FasL was detected in 3 (9.7%) adenocarcinoma and 1 (11%) AAH specimen.
These findings suggest that COX-2 might play a role in the progression from AAH to adenocarcinoma.
Anticancer research 01/2003; 23(6D):5069-73. · 1.71 Impact Factor
[show abstract][hide abstract] ABSTRACT: Breast-conserving surgery and postoperative radiotherapy have played important roles in the treatment of early breast cancer. Bronchiolitis obliterans organizing pneumonia (BOOP) syndrome has recently been reported to be one of the complications of adjuvant radiotherapy. The purpose of this study was to determine the incidence of and risk factors for BOOP syndrome in breast cancer patients.
Between January 1996 and December 1998, 157 patients with breast cancer underwent radiotherapy after breast-conserving surgery. The criteria used for the diagnosis of BOOP syndrome were as follows: 1) radiation therapy to the breast within 12 months, 2) general and/or respiratory symptoms lasting for at least 2 weeks, 3) radiographic lung infiltrates outside the radiation port, and 4) no evidence of a specific cause.
BOOP syndrome developed in 4 (2.5%) patients, who had fever and nonproductive cough, with patchy infiltrative shadows on chest roentgenograms which emerged between 5 and 6 months after radiotherapy. The symptoms and pulmonary infiltrates were rapidly improved by treatment with prednisone (40 mg/day), which was tapered over 2- to 5-month periods. However, BOOP syndrome relapsed in all cases during the tapering period or after withdrawal of prednisone. The eosinophil and neutrophil counts were increased and the ratios of CD4+ to CD8+ lymphocytes were elevated in bronchoalveolar lavage fluid in all four cases. There were no differences in proportions of patients by age, irradiated breast site, use of tamoxifen and/or chemotherapy, or radiation dose between those with and without BOOP syndrome.
BOOP syndrome is considered an intractable form of lung toxicity after radiotherapy to the breast. An immunologic reaction mediated by eosinophils, neutrophils, and lymphocytes may be responsible for the development of this syndrome. Methods of prevention of BOOP syndrome should be established.
International Journal of Radiation OncologyBiologyPhysics 11/2000; 48(3):751-5. · 4.52 Impact Factor
[show abstract][hide abstract] ABSTRACT: We describe two cases of atypical carcinoid of the thymus. One was an 82-year-old woman with complaints of nonproductive cough and back pain, and the other a 64-year-old woman with no symptoms. Computed tomography scans of the chest in both cases revealed a large mass in the anterior mediastinum. Multiple metastases to bone and liver were also noted in the former case. Histological examination of their tumors revealed that the tumor cells were arranged in a nested, trabecular, or pseudorosette pattern, with increased numbers of mitoses, nuclear pleomorphism, and presence of necrosis. In addition, immunohistochemically, the cells stained for neuron-specific enolase, synaptophysin and chromogranin A. Combination chemotherapy consisting of carboplatin and etoposide was performed as initial chemotherapy in the former case and as adjuvant therapy in the latter. The former patient achieved a short-term partial response. It is important to differentiate atypical carcinoid from other thymic tumors, since such tumors including thymoma have a much better prognosis than does atypical carcinoid.
Internal Medicine 11/2000; 39(10):834-8. · 0.97 Impact Factor
[show abstract][hide abstract] ABSTRACT: To evaluate the nature and scope of treatment for non-small cell lung cancer (NSCLC) in the elderly, we retrospectively analyzed the cases of 166 patients (aged 75 years or more) who had been treated at our hospital between 1986 and 1997. In addition, we assessed the effectiveness and feasibility of combination chemotherapy consisting of ifosfamide and vindesine for 21 elderly patients. As their initial treatment, 20 patients (12%) received surgery; 65 (39%), curative chest radiotherapy; 30 (18%), chemotherapy; and 51 (31%), best supportive care. With combination chemotherapy consisting of ifosfamide (1.6 g/m2 on hospital days 1 through 3) and vindesine (2.5 mg/m2 on days 1 and 8), the response rate was 48% and the median survival time was 13.9 months (95% confidence interval: 5.6-22.2). Grade 3 or 4 leukopenia and neutropenia developed in 76% and 86% of the patients, respectively. However, other toxicities were generally mild, and no treatment-related deaths were observed. The combination of ifosfamide with vindesine may be effective for selected elderly NSCLC patients, and warrants further clinical study.
Nihon Kokyūki Gakkai zasshi = the journal of the Japanese Respiratory Society. 05/2000; 38(4):273-7.
[show abstract][hide abstract] ABSTRACT: The clinicopathologic characteristics of atypical adenomatous hyperplasia (AAH) remain unclear. A total of 137 patients underwent resection for adenocarcinoma of the lung at our institution. Examination of resected lung tissue showed that in addition to adenocarcinoma AAH was present in 26 cases and was not present in 111 cases. All nonsmokers with AAH (n = 13) had earlier-stage disease (stage IA, IB, IIA, and IIB) and no history of respiratory disease. Among patients with stage IA disease, the relapse-free and overall survival curves for those with AAH (n = 14) tended to be better than for those without AAH (n = 40), but the difference was not statistically significant (P = 0.056 and 0.087, respectively). Concurrent presence of AAH may be a favorable prognostic indicator in patients with stage IA adenocarcinoma.
Lung Cancer 09/1999; 25(2):115-21. · 3.39 Impact Factor
[show abstract][hide abstract] ABSTRACT: Bronchioloalveolar carcinoma (BAC) has been reported to have unique clinicopathological features.
This retrospective study was performed using data base including 871 patients treated for primary lung cancer between 1981 and 1995.
The patients with BAC included a larger proportion of female (P = 0.029) and smoked less (P = 0.002) than those with non-BAC. There was no difference in survival between surgically resected patients with BAC and those with non-BAC. Clinical Stage IV patients with BAC had a better response to chemotherapy than did those with non-BAC. Survival in the former group was better than that in the latter on univariate analysis, but the significance of this difference was not confirmed multivariate analysis.
The patients with BAC included a larger proportion of females and smoked less than those with non-BAC. Treatment results for BAC was comparable to those for non-BAC.
Anticancer research 01/1999; 19(2B):1369-73. · 1.71 Impact Factor
[show abstract][hide abstract] ABSTRACT: Gefitinib ('Iressa, ZD1839) has promising antitumor activity in non-small cell lung cancer (NSCLC). However, patients with advanced NSCLC have few treatment options available if they are refractory to gefitinib. We describe four cases of patients with advanced NSCLC who previously responded to gefitinib and obtained significant tumor regression through retreatment with other cytotoxic agents. Gefitinib might restore chemosensitivity to previously chemorefractory patients.
Anticancer research 25(1B):547-9. · 1.71 Impact Factor
[show abstract][hide abstract] ABSTRACT: The relationship between preoperative serum carcinoembryonic antigen (CEA) level and treatment outcome for 39 clinical-stage I patients with surgically resected non-small-cell lung cancer (NSCLC) was retrospectively studied. Serum CEA levels were measured with an enzyme-linked immunosorbent assay kit, with the upper limit of normal defined as 6.7 ng/mL based on the 95% specificity level for benign lung disease in our hospital. Patients with serum CEA > or = 6.7 ng/mL (n = 9) were more likely to have advanced disease at surgery than those with serum CEA < 6.7 ng/mL (n = 30) (77.8% vs 16.7%, p = 0.0049). This increase in disease stage at surgery was mainly due to mediastinal lymph node metastasis. The sensitivity and specificity of serum CEA in the detection of pathological N2 disease were 62.5% and 87.1%, respectively. Survival for the high CEA group was significantly worse than that for the low CEA group (median survival time, 40.2 vs 75.8 months, p = 0.0125). Relapse-free survival for the high CEA group was also poorer than that of the low CEA group (p = 0.0032). In a multivariate analysis, serum CEA level was the most dominant factor affecting relapse-free survival (hazard ratio = 6.68, p = 0.0053). These findings suggest that preoperative serum CEA level is useful not only in detection of mediastinal lymph node metastasis, but also in prediction of survival for clinical-stage I patients with NSCLC.
Anticancer research 20(3B):2177-80. · 1.71 Impact Factor
[show abstract][hide abstract] ABSTRACT: The aim of this study was to investigate the prognostic value of hypermethylation of tumor suppressor genes in patients with non-small cell lung cancer (NSCLC). In samples from 34 lung patients with malignant pleural effusions, we used a methylation-specific polymerase chain reaction to detect aberrant hypermethylation of the promoters of the DNA repair gene O6-methylguanine-DNA methyltransferase (MGMT), p16INK4a, ras association domain family 1A (RASSF1A), apoptosis-related genes, death-associated protein kinase (DAPK), and retinoic acid receptor beta(RARbeta). There is no association between methylation status of five tumor suppressor genes including MGMT, p16INK4a, RASSF1A, DAPK and RARbeta in pleural fluid DNA and clinicopathological parameters including clinical outcome. Aberrant promoter methylation of tumor suppressor genes in pleural fluid DNA could not be a valuable prognostic marker of NSCLC patients with malignant pleural effusion.
Asian Pacific journal of cancer prevention: APJCP 8(2):221-4. · 1.27 Impact Factor