Biomedical subjects

Seiji Niho

Publications and source records attributed to Seiji Niho.

13 recordsLinked to original sources

PubMed2006

Randomized trial of drip infusion versus bolus injection of vinorelbine for the control of local venous toxicity.

Vinorelbine is a moderate vesicant that is well known to cause local venous toxicity such as drug induced-phlebitis. We conducted a prospective randomized trial to determine whether a 1-min bolus injection (1 min bolus) of vinorelbine reduced the incidence of local venous toxicity compared with a 6-min drip infusion (6 min infusion). Non-small cell lung cancer patients who were to receive chemotherapy containing vinorelbine were randomly assigned to receive either 6 min infusion or 1 min bolus of the drug. All infusions were administered through a peripheral vein. Local venous toxicity was evaluated at each infusion up to two cycles. Eighty-three patients were randomized into the study and 81 of them assessable for analysis. One hundred thirty-eight infusions to 40 patients in 6 min infusion and 135 infusions to 41 patients in 1 min bolus were delivered. Vinorelbine induced-local venous toxicity was observed in 33% of patients in 6 min infusion and 24% in 1 min bolus. There was no statistically significant difference between the two arms (P=0.41). The incidence of local venous toxicity per infusions was 16% (22 of 138 infusions) in 6 min infusion and 11% (15 of 135 infusions) in 1 min bolus (P=0.47). No severe local venous toxicity was seen in either arm. In this study, the administration of in 1 min bolus of vinorelbine did not significantly reduce the incidence of local venous toxicity compared with 6 min infusion. Further studies for the control of local venous toxicity of vinorelbine are warranted.

Adult↗

PubMed2006

Interstitial shadow on chest CT is associated with the onset of interstitial lung disease caused by chemotherapeutic drugs.

OBJECTIVE: Pretreatment computerized tomography (CT) films of the chest was studied to clarify the influence of interstitial shadow on developing interstitial lung disease (ILD). METHODS: Eligible patients were those lung cancer patients who started to receive first-line chemotherapy between October 2001 and March 2004. Patients who received thoracic radiotherapy to the primary lesion, mediastinum, spinal or rib metastases were excluded. We reviewed pretreatment conventional CT and plain X-ray films of the chest. Ground-glass opacity, consolidation or reticular shadow without segmental distribution was defined as interstitial shadow, with this event being graded as mild, moderate or severe. If interstitial shadow was detected on CT films of the chest, but not via plain chest X-ray, it was graded as mild. Patients developing ILD were identified from medial records. RESULTS: A total of 502 patients were eligible. Mild, moderate and severe interstitial shadow was identified in 7, 8 and 5% of patients, respectively. A total of 188 patients (37%) received tyrosine kinase inhibitor (TKI) treatment, namely gefitinib or erlotinib. Twenty-six patients (5.2%) developed ILD either during or after chemotherapy. Multivariate analyses revealed that interstitial shadow on CT films of the chest and treatment history with TKI were associated with the onset of ILD. CONCLUSIONS: It is recommended that patients with interstitial shadow on chest CT are excluded from future clinical trials until this issue is further clarified, as it is anticipated that use of chemotherapeutic agents frequently mediate onset of ILD in this context.

Adult↗

PubMed2006

First-line single agent treatment with gefitinib in patients with advanced non-small-cell lung cancer: a phase II study.

PURPOSE: We conducted a phase II study of single agent treatment with gefitinib in chemotherapy-naïve patients with advanced non-small-cell lung cancer (NSCLC) to assess its efficacy and toxicity. PATIENTS AND METHODS: Patients received 250 mg doses of gefitinib daily. Administration of gefitinib was terminated if partial response (PR) was not achieved within 8 weeks or if tumor reduction was not observed within 4 weeks. In these cases, platinum-based doublet chemotherapy was given as a salvage treatment. We evaluated mutation status of the epidermal growth factor receptor (EGFR) gene in cases with available tumor samples. RESULTS: Forty-two patients were enrolled between March and November 2003, with 40 of these patients being eligible. The response rate was 30% (95% CI, 17% to 47%). The most common toxicity included grade 1 or 2 acne-like rash (50%) and grade 1 diarrhea (18%). Grade 2 or 3 hepatic toxicity was observed in 8% of patients. Four patients developed grade 5 interstitial lung disease (ILD). Thirty patients received second-line chemotherapy. Median survival time was 13.9 months (95% CI, 9.1 to 18.7 months), and the 1-year survival rate was 55%. Tumor samples were available in 13 patients, including four cases of PR, six cases of stable disease, and three cases of progressive disease. EGFR mutations (deletions in exon 19 or point mutations [L858R or E746V]) were detected in four tumor tissues. All four patients with EGFR mutation achieved PR with gefitinib treatment. CONCLUSION: Single agent treatment with gefitinib is active in chemotherapy-naïve patients with advanced NSCLC, but produces unacceptably frequent ILD in the Japanese population.

Adult↗

PubMed2005

A phase II study of hyperfractionated accelerated radiotherapy (HART) after induction cisplatin (CDDP) and vinorelbine (VNR) for stage III non-small-cell lung cancer (NSCLC).

PURPOSE: The purpose was to assess the feasibility and efficacy of hyperfractionated accelerated radiotherapy (HART) after induction chemotherapy for Stage III non-small-cell lung cancer. METHODS AND MATERIALS: Treatment consisted of 2 cycles of cisplatin 80 mg/m(2) on Day 1 and vinorelbine 25 mg/m(2) on Days 1 and 8 every 3 weeks followed by HART, 3 times a day (1.5, 1.8, 1.5 Gy, 4-h interval) for a total dose of 57.6 Gy. RESULTS: Thirty patients were eligible. Their median age was 64 years (range, 46-73 years), 24 were male, 6 were female, 8 had performance status (PS) 0, 22 had PS 1, 9 had Stage IIIA, and 21 had Stage IIIB. All but 1 patient completed the treatment. Common grade > or =3 toxicities during the treatment included neutropenia, 25; infection, 5; esophagitis, 5; and radiation pneumonitis, 3. The overall response rate was 83%. The median survival was 24 months (95% confidence interval [CI], 13-34 months), and the 2-year overall survival was 50% (95% CI, 32-68%). The median progression-free survival was 10 months (95% CI, 8-20 months). CONCLUSION: Hyperfractionated accelerated radiotherapy after induction of cisplatin and vinorelbine was feasible and promising. Future investigation employing dose-intensified radiotherapy in combination with chemotherapy is needed.

Aged↗

PubMed2005

Pitfalls in lymph node staging with positron emission tomography in non-small cell lung cancer patients.

BACKGROUND: The evidence of clinical value of positron emission tomography (PET) with fluorine-18 fluorodeoxyglucose (FDG) in lymph node (LN) staging in non-small cell lung cancer (NSCLC) has been shown in numerous papers. However, few studies have assessed its limitations. The aim of the present study is to clarify clinico-pathologic factors responsible for false PET results. METHODS: From July 2000 through December 2001, 71 NSCLC patients underwent both FDG PET and surgical intervention at the National Cancer Center Hospital East, Chiba. Clinical records, computed tomographic (CT) scan findings, PET findings, and histologic findings were retrospectively reviewed. RESULTS: Sensitivity, specificity, accuracy in nodal staging for CT were 29, 83, and 65% and for PET were 39, 79, and 66%, respectively. There were 10 (14%) false-positive PET scans and 14 (20%) false-negative PET scans. The causative factors for false-positive PET scan were: (1) inflammatory conditions in seven patients; (2) PET mis-localization of an interlobar LN as a mediastinal LN in one patient; (3) inability to distinguish the endobronchial polypoid growth of a primary tumor from a lobar LN in one patient; (4) unknown in one patient. All false-positive LNs due to inflammatory conditions showed reactive lymphoid hyperplasia histologically. The causative factors for false-negative PET scan were: (1) limitation of spatial resolution of the PET scanner in 12 patients (maximum tumor focus dimensions in false-negative LNs ranging from 1 to 7.5 mm, with an average of 3.4 mm); (2) PET mis-localization of a mediastinal LN as a hilar LN in one patient; (3) weak FDG uptake by microscopic tumor foci due to necrosis with massive bleeding in a metastatic LN in one patient. CONCLUSIONS: Inflammatory conditions were most responsible for false-positive PET scans, and spatial resolution limitation of FDG PET was the causative factor of false-negative PET scans. Recognizing these factors in advance would be clinically helpful in accurate nodal staging with FDG PET.

Adult↗

PubMed2004

Comparison of pharmacokinetics and pharmacodynamics of docetaxel and Cisplatin in elderly and non-elderly patients: why is toxicity increased in elderly patients?

PURPOSE: Following phase I studies of docetaxel and cisplatin in patients with non-small-cell lung cancer, the recommended doses of docetaxel were different for elderly (> or = 75 years) and non-elderly (< 75 years) patients. To elucidate the mechanism of the difference, the pharmacokinetics of docetaxel and cisplatin were investigated in two phase II studies separately conducted in elderly and non-elderly patients. PATIENTS AND METHODS: Twenty-seven elderly and 25 non-elderly patients were treated with three weekly administrations of docetaxel and cisplatin every 4 weeks. Doses of docetaxel were 20 and 35 mg/m(2) for elderly and non-elderly patients, respectively. All patients received 25 mg/m(2) of cisplatin. The pharmacokinetics and pharmacodynamics of docetaxel and cisplatin were compared in elderly and non-elderly patients. RESULTS: There were no differences in pharmacokinetics of docetaxel or cisplatin between elderly versus non-elderly patients with regard to clearance and volume of distribution. In the pharmacodynamic analysis, neutropenia was positively correlated with the area under the concentration-time curve for docetaxel but not for cisplatin. In evaluating the relationship between neutropenia and the area under the concentration-time curve of docetaxel, elderly patients experienced greater neutropenia than those predicted by a pharmacodynamic model developed in non-elderly patients; the residual for prediction of the percent change in neutrophil count was -11.2% (95% CI, -21.8 to -0.5%). CONCLUSION: The pharmacokinetics of docetaxel and unchanged cisplatin were not different between elderly and non-elderly patients. The elderly patients were more sensitive to docetaxel exposure than the non-elderly patients, resulting in the different recommended doses for the phase II studies.

Adult↗

PubMed2004

Randomized trial of oral versus intravenous antibiotics in low-risk febrile neutropenic patients with lung cancer.

BACKGROUND: Neutropenic fever is one of the most serious adverse effects of cancer chemotherapy. Neutropenia may cause a life-threatening bacterial infection. Therefore, febrile neutropenic inpatients are empirically treated with intravenous broad-spectrum antibiotics. Recently, several studies have suggested the presence of low-risk groups among febrile neutropenic patients. METHODS: A prospective randomized trial was conducted to compare treatment with oral ciprofloxacin (200 mg) and amoxicillin-clavulanate (375 mg) administered every 8 h against that with intravenous ceftazidime (1 g) administered every 12 h in low-risk febrile neutropenic patients with lung cancer. All patients received chemotherapy and antibiotic therapy while being hospitalized. RESULTS: A total of 177 patients with lung cancer agreed to participate in this study prior to undergoing chemotherapy. Among them, a total of 36 neutropenic patients with 42 febrile episodes were enrolled in the study. Treatment was successful without the need for modification in 91% of the episodes in patients receiving the oral regimen and 79% of the episodes in patients receiving the intravenous regimen. No treatment-related deaths occurred. One patient developed nausea while receiving the oral regimen, so the oral regimen was changed to the intravenous regimen in this patient. CONCLUSIONS: This prospective study suggested that treatment with oral antibiotics ciplofloxacin plus amoxicillin-clavulanate was effective for low-risk febrile neutropenic patients after chemotherapy.

Administration, Oral↗

PubMed2004

High body mass index correlates with increased risk of venous irritation by vinorelbine infusion.

BACKGROUND: Vinorelbine is currently one of the most active chemotherapeutic agents. However, it is also a moderate vesicant that is well known to cause venous irritation and phlebitis. We conducted this study to identify clinical risk factors related to the incidence of venous irritation caused by peripheral vinorelbine infusion. METHODS: Medical records were used to investigate retrospectively a total of 201 cases of non-small cell lung cancer treated with a chemotherapeutic regimen containing vinorelbine. Venous irritation was evaluated in every course and graded according to the National Cancer Institute Common Toxicity Criteria version 2.0. Gender, age, body mass index (BMI), chemotherapeutic regimen, dose of vinorelbine and prior chemotherapy were used as clinical variables. RESULTS: A total of 928 vinorelbine infusions were administered to the 201 patients, among whom venous irritation occurred in 63 (31%). The incidence of venous irritation was 28% in the normal BMI (<25) group and 45% in the high BMI (25 or more) group and the difference between the two groups was statistically significant (P = 0.037). There were no significant correlations between the incidence of venous irritation and the clinical variables except BMI. In the multivariate analysis BMI was also a significant independent variable that correlated with increased risk of venous irritation (P = 0.017). CONCLUSIONS: Care is required when using vinorelbine to treat patients with a high BMI, especially with regard to the development of venous irritation.

Adult↗

PubMed2003

Weekly chemotherapy with cisplatin, vincristine, doxorubicin, and etoposide is an effective treatment for advanced thymic carcinoma.

BACKGROUND: Thymic carcinoma is a rare neoplasm that often disseminates or metastasizes. The role of chemotherapy in treating this malignancy is unclear. The purpose of the current study was to determine the efficacy and tolerability of a weekly chemotherapy regimen consisting of cisplatin, vincristine, doxorubicin, and etoposide (CODE) for the treatment of advanced thymic carcinoma. METHODS: The authors retrospectively reviewed 18 patients with thymic carcinoma who were treated between 1996 and 2002. Twelve of these patients had unresectable advanced diseases and received weekly chemotherapy according to the CODE regimen. The CODE regimen consisted of cisplatin (25 mg/m(2), intravenously [i.v.]; weekly administration), vincristine (1 mg/m(2), i.v.; administered during Weeks 1, 2, 4, 6, and 8), doxorubicin (40 mg/m(2), i.v.; administered during Weeks 1, 3, 5, 7, and 9), and etoposide (80 mg/m(2), i.v.; administered for 3 days during Weeks 1, 3, 5, 7, and 9). RESULTS: The responses of all 12 patients to the CODE regimen were assessed. A partial response was achieved in 5 patients, and the overall response rate was 42%. Only one patient experienced disease progression. The median progression-free survival period was 5.6 months (range, 2-39 months). The overall survival period ranged from 6 to 79 months, with a median survival period of 46 months. Based on the Kaplan-Meier method, the estimated 1-year and 2-year survival rates were 80% and 58%, respectively. The most common side effects were hematologic toxicities, and only mild nonhematologic toxicities were experienced. CONCLUSIONS: Weekly chemotherapy treatments according to the CODE regimen were effective and tolerated by patients with advanced thymic carcinoma.

Adult↗

PubMed2003

Combination second-line chemotherapy with gemcitabine and docetaxel for recurrent non-small-cell lung cancer after platinum-containing chemotherapy: a phase I/II trial.

PURPOSE: In a randomized trial, docetaxel monotherapy yielded longer survival than the best supportive care in patients with non-small-cell lung cancer (NSCLC) previously treated with platinum-based chemotherapy, and combination chemotherapy regimens containing docetaxel have been assessed to enhance the efficacy of second-line chemotherapy. We conducted a phase I/II trial of gemcitabine and docetaxel in patients with recurrent NSCLC after platinum-based chemotherapy and with an ECOG performance status (PS) of 0 or 1. PATIENTS AND METHODS: Docetaxel administration was fixed at a dosage of 60 mg/m(2) on day 8, and gemcitabine was administered on days 1 and 8. The starting dose level of gemcitabine was 800 mg/m(2) (level 0), and the subsequent dose level of gemcitabine was 1000 mg/m(2) (level +1). Treatment was repeated every 3 weeks. RESULTS: In the phase I study, 13 patients were enrolled, and in the phase II study, 29 patients were enrolled. Neutropenic fever and omission of treatment on day 8 due to leukopenia (leukocyte count less than 3000/mm(3)) were dose-limiting toxicities (DLTs). Three of six patients experienced DLTs at level +1, which was the maximum tolerated dose. Gemcitabine 800 mg/m(2) on days 1 and 8 plus docetaxel 60 mg/m(2) on day 8 (level 0) was recommended for the phase II study. An objective response was observed in 8 (28%) of the 29 patients. The median time to disease progression was 4.2 months (95% CI 0.9-7.7 months). The median survival time was 11.1 months (95% CI 9.9-12.4 months), and the 1-year survival rate was 41%. The most common toxicity, though mild, was hematologic, and consisted of grade 4 neutropenia (18%), grade 3 febrile neutropenia (11%), and grade 3 thrombocytopenia (11%). There were no toxic deaths. Grade 3 non-hematologic toxicities included nausea (4%) and rash (4%). CONCLUSIONS: The combination chemotherapy of gemcitabine and docetaxel is active and well tolerated in patients with recurrent NSCLC after platinum-based chemotherapy and with a good PS.

Adult↗

PubMed2003

Cushing's syndrome associated with adenocarcinoma of the lung.

Paraneoplastic Cushing's syndrome caused by ectopic adrenocorticotropin production has been reported in association with a variety of malignant tumors. However, most cases of this syndrome are associated with neuroendocrine tumors such as small-cell lung cancer (SCLC), carcinoid tumors, and medullary carcinoma of the thyroid. We present a 49-year-old man who developed Cushing's syndrome associated with adenocarcinoma of the lung. He had a wide variety of clinical symptoms and comorbidity related to this syndrome during the course, and died 4 months after the diagnosis. This is a very rare case report of Cushing's syndrome associated with adenocarcinoma of the lung.

ACTH Syndrome, Ectopic↗

PubMed2002

Phase II study of docetaxel and cisplatin administered as three consecutive weekly infusions for advanced non-small cell lung cancer.

Weekly administration of low-dose taxane reduces myelosuppression and increases dose intensity as compared with an every third week schedule. We conducted a phase II trial of weekly docetaxel and cisplatin in patients with advanced non-small cell lung cancer (NSCLC) to evaluate safety and efficacy. Thirty-seven patients with chemonaïve stage IIIB (n=15), stage IV (n=16), or recurrence after operation (n=6) NSCLC received intravenous infusions of docetaxel at 35 mg/m(2) and cisplatin at 25 mg/m(2) for three consecutive weeks, followed by a week of rest. There were ten partial responses for an objective response rate of 30% (95% confidence interval (CI), 15-46%) in 33 evaluable patients and 27% (95% CI, 13-41%) in the intent-to-treatment population. The median survival was 12.8 months (range 2.5-17.1), and the 1-year survival was 54%. Hematologic toxicities, which were mild, included grade 4 neutropenia in 6%. There were none with febrile neutropenia or severe (grade 3-4) infections, and no septic deaths. The common nonhematologic toxicities included grade 2-3 nausea and vomiting (44%) and grade 2-3 diarrhea (14%). Consecutive weekly administrations of docetaxel and cisplatin for 3 weeks produces minimal myelosuppression and shows activity in the treatment of chemonaïve patients with advanced NSCLC. A randomized phase III trial is warranted to compare this 3 consecutive weeks protocol with administration of docetaxel and cisplatin every third week.

Adult↗

PubMed2002

Three novel single nucleotide polymorphisms in UGT1A10.

Three novel single nucleotide polymorphisms (SNPs) were found in the UDP-glucuronosyltransferase (UGT) 1A10 gene from 24 Japanese patients with various cancers who were administered the anti-tumor drug, irinotecan (CPT-11). The detected SNPs were as follows: 1) SNP, MPJ6_U1A003; GENE NAME, UGT1A10; ACCESSION NUMBER, AF297093; LENGTH, 25 bases; 5'-CAGATGCCATGAC/TTTTCAAGGAGAG-3'. 2) SNP, MPJ6_U1A004; GENE NAME, UGT1A10; ACCESSION NUMBER, AF297093; LENGTH, 25 bases; 5'-CCTAGAAATAGCC/TTCTGAAATTCTC-3'. 3) SNP, MPJ6_U1A030; GENE NAME, UGT1A10; ACCESSION NUMBER, AF297093; LENGTH, 25 bases; 5'-GGTTGTAGTCATG/ACCAGAGGTGAGT-3' All the three SNPs were located in exon 1 and their frequencies were all 0.021. Among these SNPs, MPJ6_U1A003 and U1A030 resulted in amino acid alterations, T202I and M59I, respectively. The third SNP, MPJ6_U1A004, introduced a synonymous amino acid change (A231A).

Journal Article↗