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Biomedical subjects

K Furuse

Publications and source records attributed to K Furuse.

At least 55 records · Page 3Linked to original sources

A pilot study of concurrent whole-brain radiotherapy and chemotherapy combined with cisplatin, vindesine and mitomycin in non-small-cell lung cancer with brain metastasis.

We have evaluated the feasibility, toxicity, and tumour response of concurrent whole-brain radiotherapy (WBRT) and chemotherapy with cisplatin, vindesine and mitomycin in the treatment of 33 patients with brain metastasis from non-small-cell lung cancer (NSCLC). The imaging response demonstrated that 25 patients (75.8%) responded to brain lesions, including five complete responders, and the response rate to primary lesion was 18%. The treatment improved at least one grade of performance status in 30% and of neurological functions in 55% of the patients. The major toxicity was leucopenia (> or = grade 3, 84.4%). Median survival was 9.7 months and the 1-year survival rate was 40%. Concurrent WBRT and chemotherapy can be safely administered to patients with brain metastasis from NSCLC, with a remarkable response rate, improvement of neurological functions and encouraging survival duration.

Adult↗

CODE chemotherapy with and without granulocyte colony-stimulating factor in small-cell lung cancer.

Sixty-three patients with extensive-stage small-cell lung cancer were randomized to receive either cyclophosphamide, vincristine, doxorubicin and etoposide (CODE) alone or CODE plus recombinant human granulocyte colony-stimulating factor (rhG-CSF). rhG-CSF administration in support of CODE chemotherapy resulted in increased mean total received dose intensity for all drugs (P = 0.03) with a significant improvement in survival (P = 0.004).

Adult↗

Prognostic factors and prognostic staging system for small cell lung cancer.

This study was performed to assess the prognostic factors and the predictors of long-term (3-year) survival in patients with small cell carcinoma of the lung, accrued in one randomized trial, and to define patient subgroups showing significantly different survivals using recursive partitioning and amalgamation analysis. A total of 300 patients with small cell carcinoma of the lung were entered into a randomized study comparing cyclophosphamide, adriamycin and vincristine (CAV), cisplatin and etoposide (PE) and alternating treatments of CAV and PE. Of these, 286 patients were analysed for the present study of prognostic factors. Multivariate analysis showed that poor performance status (2-3) (P = 0.0001), extensive disease (P = 0.0015) and abnormally elevated serum lactate dehydrogenase (P = 0.0001) and alkaline phosphatase (P = 0.0013) were independently adverse pretreatment prognostic factors. Of limited disease patients, performance status (P = 0.029) and white blood cell count (P = 0.044) had a significant influence on the probability of 3-year disease-free survival. Using recursive partitioning and amalgamation analysis, three classes of similar prognosis were identified: the most favorable class was defined by knowledge of lactate dehydrogenase (normal), performance status (0-1) and serum sodium levels (normal) with median survival time of 16.0 months, and the class with the poorest prognosis was defined by knowledge of lactate dehydrogenase (elevated) and performance status (2-3) (median survival time 6.6 months). The intermediate class had a median survival time of 9.4 months. In conclusion, this subclassification system will be used for the design, implementation and interpretation of clinical studies as well as decision-making in individual patients.

Adult↗

Utility of hyaluronic acid in pleural fluid for differential diagnosis of pleural effusions: likelihood ratios for malignant mesothelioma.

The level of hyaluronic acid (HA) was determined in the pleural fluid of 99 patients, including 19 with malignant mesothelioma, 27 with lung cancer, 1 with breast cancer, 1 with mediastinal tumor and 51 with non-malignant diseases. With a cut-off level at 100 micrograms/ml, the pleural fluid concentration of HA was high in 36.8% of patients (7 of 19) with malignant mesothelioma and 1.3% of patients (1 of 80) with lung cancer and other malignant and non-malignant diseases. The mean concentration of pleural fluid HA was significantly higher in patients with mesothelioma than in those with lung cancer and other malignant and non-malignant diseases. The pre-test probability of MM was 5.9% in this series. The LRs for > or = 100, 50-99 and < or = 49 micrograms/ml are 28.3, 3.3 and 0.5, respectively; these put the post-test probabilities at 64, 17 and 3%, respectively. Indeed, in cases of uncommon disease such as MM, the post-test probability is low even if the cut-off level of HA is > or = 100 micrograms/ml. The discrimination between malignant mesothelioma and lung cancer needs special attention. In these two diseases, the LRs of MM for pleural fluid CEA > 30, 10-30 and < 10 ng/ml were 0.2, 1.9 and 2.4, respectively. The pre-test probability of MM for HA > or = or 100 micrograms/ml is 64%. Furthermore, because the LR for CEA is < 10 ng/ml, the post-test probability is 81%. When the combination of two markers is considered, the high level of HA and the low level of CEA may be useful for the differential diagnosis of MM from pleuritis carcinomatosa.

Biomarkers, Tumor↗

Identification of chitinase and osmotin-like protein as actin-binding proteins in suspension-cultured potato cells.

Cytoplasmic aggregation is an early resistance-associated event that is observed in potato tissues either after penetration of an incompatible race of Phytophthora infestans, the potato late blight fungus, or after treatment with hyphal wall components (HWC) prepared from P. infestans. In potato cells in suspension culture, the number of cells with cytoplasmic aggregation increased upon treatment with HWC, but such an increase was suppressed by treatment with cytochalasin D prior to treatment with HWC. This result suggested that cytoplasmic aggregation in cultured potato cells might be connected with the association of actin filaments. To identify the molecular basis of cytoplasmic aggregation, we purified actin and actin-related proteins by affinity chromatography on a column of immobilized DNase I from cultured potato cells and isolated proteins of 43 kDa, 32 kDa and 22 kDa. Analysis of the amino-terminal amino acid sequences indicated that the 43 kDa, 32 kDa and 22 kDa proteins were potato actin, basic chitinase and osmotin-like protein, respectively. This conclusion was supported by the results of Western blotting analysis of the 43 kDa and 32 kDa proteins with antibodies against actin and basic chitinase. Binding analysis with actin coupled to actin-specific antibodies and biotinylated actin suggested that the 32 kDa and 22 kDa proteins had actin-binding activity. In addition, examination of biomolecular interactions using an optical biosensor confirmed the binding of chitinase to actin. These results imply the possibility that basic chitinase and osmotin-like protein might be involved in cytoplasmic aggregation, hereby participating. In the potato cell's defense against attack by pathogen.

Amino Acid Sequence↗

[Clinical evaluation of 2 mg granisetron tablet for nausea and vomiting induced by anticancer drugs including cisplatin].

1. The clinical efficacy and safety of the 2 mg granisetron tablet were assessed in 32 mainly lung cancer patients who were to receive treatment with anticancer drugs including CDDP. 2. One 2 mg granisetron tablet was administered prophylactically one hour before the start of CDDP administration. 3. Based on the development of nausea and vomiting in 24 hours after the start of CDDP administration, the study medication was judged to be "remarkably effective" or "effective" in 71.0% (22/31) of cases. 4. The study medication was judged to be "safe" in 96.9% (31/32) of cases, without causing any adverse reactions. 5. The above results indicate that the 2 mg granisetron tablet is safe and useful.

Adult↗

[Correlation between the tumor marker Pro-GRP and prognosis in patients with small-cell lung cancer].

We studied 90 patients with small-cell lung cancer in whom levels of Pro-GRP were abnormally high before therapy. Changes in the serum Pro-GRP level have been said to correlate strongly with therapeutic responses in patients with small-cell lung cancer. We found that changes in the serum Pro-GRP level (half-life > or = 30 vs < 30 days) were a significant prognostic factor. Multivariate analysis showed that in these patients the Pro-GRP level after therapy, Performance Status, and age were independent prognostic factors.

Adult↗

[Lung cancer].

Recently, a number of novel chemotherapeutic agents under development show consider able promise in the treatment of lung cancer. Optimally, these new agents should exhibit a unique mechanism of action, a favorable toxicity profile in comparison to standard cisplatin-based chemotherapy, significant single agent activity (> 20% response rate, or > 40% 1-year survival rate) and synergistic antitumor effects with cisplatin and/or radiation. This review will describe the current development status of these new agents, including paclitaxel, docetaxel, vinorelbine, CPT-11, topotecan and gemcitabine.

Antimetabolites, Antineoplastic↗

[The recent progress in chemoradiotherapy of lung cancer].

This is a review of the recent progress in chemoradiotherapy of locally advanced lung cancer. In the limited disease stage of small cell lung cancer, a meta-analysis showed patients treated with a combination of chemotherapy and radiotherapy have a statistically significantly longer survival than those with chemotherapy alone. However, the timing of the combination of radiation and chemotherapy has not been clarified. One study favored late over early use of radiotherapy for survival. Another randomized study and a meta-analysis revealed earlier radiotherapy had a better prognosis. JCOG performed a randomized phase III study comparing concurrent chemoradiotherapy with chemotherapy followed by radiotherapy, and the final results will be published in the near future. In the past, radiotherapy alone had been considered standard therapy for inoperable locally advanced non-small cell lung cancer. Several randomized studies and meta-analyses demonstrated the combination of chemotherapy and radiotherapy produced better survival rates than by radiotherapy alone. Our randomized study indicated the addition of radiotherapy after chemotherapy is superior in long-term survival to chemotherapy alone. The West Japan Lung Cancer Group conduct a phase III randomized study comparing concurrent and sequential chemoradiotherapy, and the determination of survival is now in the follow-up stage. The role of induction chemoradiotherapy before surgical resection, comparison of chemoradiotherapy with induction chemoradiotherapy followed by surgery, and the effects and safety of the combination of new drugs and radiotherapy are now under investigation.

Antineoplastic Agents↗

Dose escalation study of carboplatin with fixed-dose etoposide plus granulocyte-colony stimulating factor in patients with small cell lung carcinoma. A study of the Lung Cancer Study Group of West Japan.

BACKGROUND: We performed a Phase I-II trial to determine the maximum tolerated dose of carboplatin (CBDCA) with a fixed dose of VP-16 and granulocyte-colony stimulating factor (G-CSF) in small cell lung cancer (SCLC) patients. METHODS: Treatment consisted of a starting dose of CBDCA, 400 mg/m2 (i.v., Day 1); VP-16, 100 mg/m2 (i.v., Days 1-3), and G-CSF, 2 micrograms/kg (s.c., Days 4-17) every 4 weeks for four cycles. The dose of CBDCA was escalated in increments of 50 mg/m2 until Grade IV toxicity on the World Health Organization scale developed in two-thirds or more of the patients. RESULTS: Seventy-five previously untreated patients with pathology confirmed SCLC were entered into the trial. Seventy-one patients were eligible and 70 patients were evaluated for response. Forty-five patients had limited disease (LD) and 26 had extensive disease (ED). The response rate of the 70 patients who could be evaluated was 81%, with 23% attaining a complete response (CR) and 58% attaining a partial response (PR). The response rate was 80% in LD patients (CR, 23%; PR, 57%) and 85% in ED patients (CR, 23%; PR, 62%). The major dose-limiting toxicity was thrombocytopenia. Nephrotoxicity, neurotoxicity, and ototoxicity were uncommon. The doses of CBDCA that resulted in unacceptable thrombocytopenia were 700 mg/m2 in patients younger than 70 years and 500 mg/m2 in patients older than 70 years. Overall median survival time (MST) was 9 months. MST of LD patients and ED patients were 11 months and 7 months, respectively. The dose-limiting toxicity of CBDCA with a fixed dose of VP-16 and using G-CSF as bone marrow rescue was age-related thrombocytopenia. The maximum tolerated dose of CBDCA was 650 mg/m2 if patients were younger than 70 years and 450 mg/m2 if they were 70 years or older. CONCLUSIONS: When we retrospectively compared our results with those using standard chemotherapy regimens, we saw no therapeutic benefit from increasing planned doses of CBDCA up to 700 mg/m2 in combination with G-CSF in patients with SCLC.

Aged↗

Clinicopathological significance of Ki-ras point mutation and p21 expression in benign and malignant exocrine tumors of the human pancreas.

CONCLUSION: The present study suggests that Ki-ras point mutations may play an important role in the early stages of tumorigenesis and that a double mutation has a stronger detrimental effect than a single mutation on the survival after pancreatectomy. BACKGROUND: Previous studies have suggested the important role of Ki-ras point mutations in ras gene codon 12 in the tumorigenesis of pancreatic cancer, but their clinicopathological significance is still unclear. The present study was designed to assess the clinicopathological significance of Ki-ras point mutations, and p21 expression in malignant and benign diseases of the pancreas. METHODS: Oligonucleotide dot-blot hybridization for Ki-ras point mutations in codon 12 and immunohistochemical staining for p21 expression were applied. Cases included 44 primary and 15 metastatic lesions of pancreatic cancer, and 17 benign pancreatic diseases. RESULTS: Ki-ras point mutations and p21 expression were detected in 43 and 19 primary lesions, 9 and 6 metastatic lesions, and four and five benign diseases, respectively. The patients with a single mutation had a better survival after pancreatectomy than those with a double mutation. The patients with a p21(+) GAT mutation showed the worst survival after pancreatectomy compared with other categories of patients.

Adult↗

Phase II study of recombinant human interleukin 3 administration following carboplatin and etoposide chemotherapy in small-cell lung cancer patients. SDZ ILE 964 (IL-3) Study.

Recombinant human interleukin 3 (rhIL-3) has been suggested to be a useful agent for the treatment of chemotherapy-induced thrombocytopenia. For evaluation of this possibility, rhIL-3 was given subcutaneously for 10 days to patients with small-cell lung cancer (SCLC). Chemotherapy consisted of carboplatin (CBDCA) given at 400 mg/m2 to previously untreated patients or at 350 mg/m2 to previously treated patients on day 1 and etoposide (VP-16) given at 100 mg/m2 on days 1-3 every 4 weeks. If the platelet count nadir was < 75,000/microliters in the control cycle of chemotherapy, patients were randomly assigned for the next cycle to rhIL-3 given at 5 or 10 micrograms/kg per day on days 4-13. A total of 41 patients (32 previously untreated patients and 9 previously treated patients) were enrolled in the study. The platelet count nadir in the cycles including rhIL-3 was significantly higher at both dose levels (P < 0.01) than in the control cycle. The duration of thrombocytopenia (< 75,000/microliters) and the mean time from the 1st day of chemotherapy to thrombocyte recovery (> 100,000/microliters) in the rhIL-3 cycle were significantly shorter than those in the control cycle (P < 0.01). The neutrophil count nadir and the duration of neutropenia (<1,000/microliters) were also significantly improved in the rhIL-3 cycle (P < 0.05). The major side effects were fever (80.5%), headache (24.3%), and fatigue (14.6%). All side effects were tolerable and of less than grade II. There was no difference in the efficacy of the two dose levels, but the 5-micrograms/kg dose appeared to be better tolerated than the 10-micrograms/ kg dose. We conclude that rhIL-3 administration following chemotherapy consisting of CBDCA and VP-16 reduces the incidence and severity of chemotherapy-induced thrombocytopenia and neutropenia with an acceptable adverse-events profile.

Adult↗

Management of malignant tracheobronchial stenosis with metal stents and Dumon stents.

BACKGROUND: Tracheobronchial stenosis caused by malignancy is a life- threatening problem. Stenting is one of the treatment modalities and recently has been used widely for the management of such stenosis, but we do not have a clear guide as to which stent should be selected. METHODS: We evaluated 25 patients (19 men, 6 women; mean age, 60.7 years; range, 34 to 77 years) received 24 metal stents (four covered with silicone rubber) and three Dumon stents. All 25 patients had severe dyspnea because of airway stenosis caused by malignant tumors. RESULTS: Among the 25 patients, airway obstruction due to extrinsic compression by tumor developed in 11 and was treated with a bare metal stent. The airway remained patent in 10 patients. In 16 patients with intraluminal tumor invasion, nine lesions were treated with a bare metal stent, four lesions with a covered metal stent, and the remaining three lesions with a Dumon stent. Recurrent stenosis did not occur in any patient with a covered metal stent or a Dumon stent. However, restenosis occurred in 4 patients with a bare metal stent, all of whom received laser therapy. In all patients, stenting immediately relieved dyspnea. Six patients lived for 32 days to 53 months after stenting, and 19 patients died of primary malignancies with a mean survival of 131.9 days. CONCLUSIONS: Metal stents are effective in treating malignant extrinsic tracheobronchial compression. The use of covered metal stents or Dumon stents is preferable for intraluminal stenosis due to malignant growth.

Adult↗

Randomized study of vinorelbine (VRB) versus vindesine (VDS) in previously untreated stage IIIB or IV non-small-cell lung cancer (NSCLC). The Japan Vinorelbine Lung Cancer Cooperative Study Group.

PURPOSE: We compared the activity of vinorelbine (VRB) and vindesine (VDS) in a randomized crossover study in patients with previously untreated stages IIIB or IV non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Two hundred four patients were assessable for response and toxicity. VRB was administered at a dose of 25 mg/m2 weekly and VDS at a dose of 3 mg/m2 weekly. Patients who failed to respond after 4 cycles of initial monotherapy were switched to a combination chemotherapy (VRB-->VDS + cisplatin (P) or VDS-->VRB + P). RESULTS: Objective response was observed in 31.1% of patients in the VRB arm versus 8.9% of those in the VDS arm (P = 0.0002). The median duration of response to VRB was 18.5+ weeks (range, 7.9 to 107.5+ weeks) compared with 11.7+ weeks (range, 6.0 to 35.0+ weeks) for VDS. Of the 69 patients who failed to respond to initial monotherapy, 33 in the VRB group who subsequently received VDS + P did not respond and 13 (26.5%) of 49 initially on VDS who received subsequent VRB + P responded. The rates of grades 3 and 4 leukopenia were similar in the two monotherapy arms (VRB, 55.3% vs. VDS, 48.5%). However, grade 3 anemia was more frequent in the patients on VRB than in those on VDS. The incidence of peripheral neurotoxicity was significantly higher with VDS than with VRB (P = 0.002), but VRB induced a slightly higher rate of local cutaneous reaction than VDS (P = 0.012). With the combination of cisplatin and these vinca alkaloids, peripheral neurotoxicity was less frequent in the VRB group than in the VDS group. CONCLUSION: Our results demonstrate that VRB yields a higher response rate than VDS in stage IIIB or IV NSCLC, with the same extent of toxicity in terms of leukocytopenia. The peripheral neurotoxic effects were also milder with VRB than with VDS. In second-line chemotherapy, there was a notable difference in response between the VRB + P and VDS + P regimens.

Adult↗

Dose-escalation study of oral etoposide and carboplatin in patients with advanced lung cancer.

A dose-escalation study of daily etoposide and carboplatin was carried out on 23 patients with advanced lung cancer using a starting dose of 40 mg/m2/day etoposide given orally for 21 days and 250 mg/m2 carboplatin given intravenously (IV) on day 1. A total of 41 courses were given. Myelosuppression was the major dose-limiting toxicity. The maximum tolerated dose was reached at the fourth level with 40 mg/m2/day etoposide for 21 days and 400 mg/m2 carboplatin on day 1, once every 4 weeks. Non-hematological toxicities were generally mild or reversible. The recommended doses of this combination chemotherapy are 40 mg/m2/day etoposide for 21 days and 350 mg/m2 carboplatin on day 1. The response rate for non-small cell lung cancer and small cell lung cancer was 16.7% and 60% (95% confidence intervals of 3.6% to 41.4%, and 14.7% to 94.7%), respectively. A phase II study is necessary to define the efficacy and safety of this combination chemotherapy.

Administration, Oral↗

A case of malignant pleural mesothelioma with metastasis to the orbit.

A 58-year-old woman with malignant mesothelioma metastatic to the orbit is reported. Malignant pleural mesothelioma was diagnosed by pleural biopsy. Marked reduction of pleural effusion was obtained with intrapleural interleukin-2 therapy. Systemic chemotherapy failed to elicit a response after the first recurrence of the tumor. Multiple systemic metastasis, including metastasis to the orbit, developed and the patient died one year and 4 months after the initial diagnosis. Although malignant mesothelioma is known to spread hematogenously, sometimes producing brain metastasis, there have been few reports of orbital metastasis, and in fact the present report may be the first clinically documented account of its kind.

Female↗

Determinants of myelosuppression in the treatment of non-small cell lung cancer with cisplatin-containing chemotherapy.

Data on 16 potential risk factors for myelosuppression were assessed in 134 patients who received either vindesine and cisplatin (VP) or mitomycin C, vindesine and cisplatin (MVP) for inoperable stage III or IV non-small cell lung cancer in a randomized trial. Determinant factors for myelosuppression were evaluated by using univariate analysis and the logistic regression model. Recursive partitioning and amalgamation (RPA) was also used to define patient subgroups frequently suffering from severe bone marrow toxicity. Overall, 33 (25%) of 134 patients experienced at least one episode of grade 4 leukopenia. In univariate analysis, age, body surface area, serum creatinine, and pretreatment hemoglobin concentration were associated with severe leukopenia. A multivariate analysis using the logistic regression method showed that only raised creatinine level was an independent predictor for grade 4 leukopenia (P = 0.049). The RPA model generated three distinct subgroups based on age, body surface area and regimen. The three subgroups were distinguished by the frequency of severe (grade 4) leukopenia (50%, 25%, and 2.4%, respectively) (P < 0.001). Grade 4 leukopenia occurred more frequently in patients in class 3 (age > or = 65 years and treatment with MVP). The RPA model was useful in identifying the risk factors for myelosuppression induced by cisplatin-based chemotherapy, and in defining patient subgroups with elevated risk of toxicity.

Adult↗