Biomedical subjects

K Furuse

Publications and source records attributed to K Furuse.

At least 91 records · Page 5Linked to original sources

PubMed1994

[Detection of Mycobacterium tuberculosis in transbronchial biopsy specimens by polymerase chain reaction].

Polymerase chain reaction (PCR) for the rapid detection of Mycobacterium tuberculosis was used to test 30 clinical specimens (transbronchial biopsy specimens) from patients in whom tuberculosis was suspected on chest X-ray. In these patients, 15 cases were histologically diagnosed as tuberculosis. Among them, M. tuberculosis was detected in 8 specimens by PCR. Of 8 PCR positive specimens, 7 were also positive by smear and culture; the other was negative by smear and positive by culture. On the other hand, 15 cases were therapeutically diagnosed as the tuberculosis and these specimens showed negative results in neither PCR nor microbiological tests. We conclude that the PCR method is useful for rapid and direct detection of M. tuberculosis in transbronchial biopsy specimens.

Biopsy↗

PubMed1994

[Phase I clinical trial of RP 56976 (docetaxel) a new anticancer drug].

A multicenter phase I clinical trial of RP 56976 (docetaxel), a new anticancer drug, was performed with single and repeated doses. Based on the results of phase I clinical trials conducted in the United States and Europe, the starting dose was 10 mg/m2. The dose was subsequently increased to 20, 50, 70 and 90 mg/m2. A dose of 60 mg/m2 was additionally tested. Single administrations of the six dose levels were performed in a total of 27 patients via intravenous drip infusion over one hour. Ten of the patients subsequently received repeated doses at three of the dose levels in the same manner. The dose limiting factor (DLF) of docetaxel is leukopenia (especially, neutropenia). Based on the observation of the DLF, the maximum tolerated dose (MTD) was determined to be 70-90 mg/m2. The white blood cell count reached a nadir about 9.5-19.5 days (median) after administration, and took 7-11 days (median) to recover. Other adverse reactions observed were nausea/vomiting anorexia, alopecia, diarrhea, fatigue and fever, which were all acceptable. The results of this trial suggest that a dosage regimen of 60 mg/m2 at 3- to 4 week intervals is appropriate in an early phase II clinical trial.

Adolescent↗

PubMed1994

Concurrent cisplatin-etoposide chemotherapy plus thoracic radiotherapy for limited-stage small cell lung cancer. Japanese Lung Cancer Chemotherapy Group in Japanese Clinical Oncology Group.

A recent approach in the treatment of limited-stage small cell lung cancer (LDSCLC) has involved a combined modality of chemotherapy and chest irradiation. In using the modality, the study of scheduling methods for combining chemotherapy and radiotherapy should lead to other trials of combined modalities against LDSCLC since it is the most basic issue to be evaluated. We have thus conducted a multicenter phase II trial of concurrent cisplatin-etoposide (PVP) chemotherapy and radiotherapy for LDSCLC to determine the effects of the concurrent administration of a PVP regimen and chest irradiation on response rate, relapse, survival and treatment toxicity. The chemotherapy regimen consisted of a four-week cycle: cisplatin (80 mg/m2, given intravenously on day 1) and etoposide (100 mg/m2, given intravenously on days 1-3). This cycle was given four to six times within six months. Chest irradiation to the primary tumors at both the hili and the mediastinum was administered in standard fractions on days 2-12 in the first cycle of chemotherapy and on days 29-47 in the second cycle, with a total dose of 40-50 Gy. Prophylactic cranial irradiation was performed among complete remission (CR) or good partial remission (PR) patients after completion of the concurrent therapy. A total of 66 patients were entered into the trial and 59 were evaluated. The concurrent therapy induced an overall response rate of 94.9% in 59 patients: 24 patients, 40.7% CR, 32 patients, 54.2% PR. The median response duration was 8.7 months, and the median survival time for all eligible patients was 14.8 months. The percentage of patients with two-year survival periods was 20. A local relapse within the irradiated area was seen in only 22% of relapse patients. Brain metastases occurred in 24% of patients. Four of 32 patients treated with prophylactic cranial irradiation had brain metastases. Toxic effects, chiefly grades 3 and 4 leukopenia, as established by the World Health Organization, were detected in all treated patients. Other toxicities, including radiation-induced esophagitis and pneumonitis, were deemed almost acceptable. We concluded concurrent treatment of a PVP regimen with chest irradiation to be a feasible and beneficial therapy with an efficacy compatible to that of other published reports. The outcome of this protocol warrants further investigation to determine the optimal type of schedule for concurrent chemoradiotherapy against LDSCLC.

Adult↗

PubMed1994

[Recent changes in the management of advanced non-small cell lung cancer].

The value of chemotherapy in advanced non-small cell lung cancer (NSCLC) has been shown in combination chemotherapy with cisplatin, which yields only marginal survival benefits. Chemoradiotherapy with cisplatin improves the survival of patients who have unresectable, locally advanced NSCLC when compared with the treatment by radiation therapy alone. The 2- and 3-year survival rates are nearly doubled on average. Neoadjuvant chemotherapy is more effective than surgery alone for the treatment of stage IIIA NSCLC in the randomized phase III trials. It is suggested that neoadjuvant chemotherapy will be a standard therapy for stage IIIA NSCLC which is marginally resectable. There are many studies about radiation methods such as hyperfractionated radiation therapy and CHART, irradiated dose, and timing of radiation. There is a need to develop new, more active anti-cancer agents, and to find more effective regimens.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1994

[Phase-I clinical study of KW-2307 combined with cisplatin in non-small cell lung cancer patients].

A phase-I clinical study with coadministration of a new vinca alkaloid derivative KW-2307 with cisplatin (CDDP) at 80 mg/m2 to patients with non-small cell lung cancer was conducted by a collaborative study among 6 institutions. CDDP was given on day 1 and KW-2307 on days 1, 8 and 15, both intravenously. One 28-day course was specified to be repeated twice. The initial dose of KW-2307 was 15 mg/m2 and increased to 20 mg/m2 and then to 25 mg/m2. The numbers of enrolled subjects for each dose were 5, 8 and 12 cases, respectively, in the total 25 cases. This regimen as well as KW-2307 monotherapy induced leukocytopenia (neutropenia) as the main adverse reaction. The coadministration with CDDP tended to increase the occurrence of anorexia and nausea/vomiting. Tumor response was obtained in 5 among 24 evaluable cases (CR1, PR 4). The response rate in the cases untreated with KW-2307 and given at 20 mg/m2 or higher doses was 29.4% (5/17, 95% confidence interval of the response rate: 10.3 to 54.7%). Considering drug compliance, etc., the maximum tolerated dose in this regimen was supposed to be 25 mg/m2, and the recommended dose in phase-II study to be 20 mg/m2.

Adenocarcinoma↗

PubMed1994

[Phase I clinical study of 21-consecutive-day oral administration of etoposide].

We conducted a multi-institutional phase I clinical study on a 21-consecutive-day oral administration of etoposide in 12 patients with malignant tumor. The initial dose was 25 mg/body/day and then raised to 50 mg/body/day and eventually to 75 mg/body/day. The dose limiting factor was leukopenia and the maximum tolerated dose (MTD) was 75 mg/body/day. Leukopenia was observed in all 4 patients registered at 75 mg/body/day. Two of 4 patients showed WBC count nadirs of less than 2,000/microliters. The two patients had less than 1.5 m2 body surface area. Thrombocytopenia and hemoglobin decrease were mild compared to leukopenia. Other adverse reactions were as follows; anorexia (75.0%), nausea/vomiting (58.3%) alopecia (46.1%). No sign of accumulation after 21-consecutive-day oral administration of etoposide was seen on pharmacokinetic parameters. As for anti-tumor efficacy, a partial response was noted in a patient with lung metastasis of cervical cancer at the 75 mg/body/day dose level. A recommended dose for phase II study was 75 mg/body/day for 21 consecutive days with a one-week interval. However, for a patient with a body surface area less than 1.5 m2 or with a severe prior chemotherapy, 50 mg/body/day would be considered appropriate.

Administration, Oral↗

PubMed1994

Coexistence of paraneoplastic sensory neuronopathy and Lambert-Eaton myasthenic syndrome in a small cell lung cancer patient.

The present report is on a 72-year-old male patient with combined paraneoplastic sensory neuronopathy (PSN) and Lambert-Eaton myasthenic syndrome (LEMS) with small cell lung cancer. He noticed a painful paresthesia of the legs which advanced over seven days, and both hands became numb and painful. Three months later, he was found to have small cell lung cancer by mediastinoscopic examination. PSN was diagnosed by clinical symptoms and anti-Hu antibody, and LEMS was diagnosed by the waxing phenomenon on an electromyogram (incremental in compound muscle action potential up to 120%) and autoantibody against the presynaptic voltage-gated calcium channel. High titers of anti-Hu antibody were detected in the serum (1:12800) and cerebrospinal fluid (1:320). Although a partial response to chemoradiotherapy was obtained, the neurologic symptoms of PSN did not improve. The anti-Hu antibody titers obtained on five different occasions during the patient's clinical course did not change. The patient died from respiratory arrest six months after the initiation of therapy. To the best of the authors' knowledge, this combined form of disease, confirmed by both clinical and laboratory tests, is the rarest case ever to be reported.

Aged↗

PubMed1994

[Late phase II clinical study of KW-2307 in previously untreated patients with non-small cell lung cancer. KW-2307 Study Group (Lung Cancer Group)].

A late Phase II clinical study of KW-2307, a new vinca alkaloid derivative, in previously untreated patients with non-small cell lung cancer was jointly carried out in 26 medical institutions. Of 80 enrolled cases, 75 cases were eligible, and PR was attained in 23 cases (30.7%). The main adverse effect of this drug, leukopenia (neutropenia), was observed in 62.7% (83.3%) of Grade 3 and 4 cases, but they recovered rapidly. In addition to decreased hemoglobin in 67% (Grade 3 in 5.7%) of the cases, adverse effects included slight disorder of hepatic function, anorexia, nausea and vomiting, fever, general fatigue, phlebitis, paresthesia and interstitial pneumonia. Peripheral neuropathy such as paresthesia occurred rarely and was slight, if any.

Adult↗

PubMed1994

[Early phase II clinical study of KW-2307 in patients with lung cancer. Lung Cancer Section in KW-2307 Study Group].

A multicenter early Phase II clinical study of KW-2307, a new vinca alkaloid derivative, in patients (pts) with lung cancer was conducted in 15 hospitals. Ninety-seven pts were enrolled, among whom 95 were eligible. Seventy of the eligible pts had non-small cell cancer (NSCLC) and 25 had small cell cancer (SCLC). PR was obtained in 13 (18.6%) of NSCLC pts and 3 (12%) of SCLC pts. Only those who had no previous chemotherapy showed PR in NSCLC pts, and the response rate in these pts was 29.5% (13/44). As to the correlation between dosage and tumor effect, a better effect was exhibited at higher doses, with response rates of 21.7% (5/23) and 38.1% (8/21) at 20 mg/m2 and 25 mg/m2, respectively. The major adverse effect of this drug was leukopenia (neutropenia), which was Grade 3 or 4 in many cases. Recovery from this complication, however, was rapid. Other adverse effects included mild hepatic dysfunction, anorexia, nausea/vomiting, fever, general fatigue, phlebitis and constipation. The incidence of peripheral nervous disorder such as the paresthesia commonly observed with vinca alkaloids, was as low as 10%, and the symptoms, if any, were mild.

Adult↗

PubMed1994

[Phase I clinical study on new vinca alkaloid derivative, KW-2307 (vinorelbine). KW-2307 Study Group].

Phase I study on a new vinca alkaloid derivative, KW-2307(vinorelbine), was conducted by multiple institutions in 40 patients with a variety of malignant tumors. KW-2307 was given intravenously by single administration or by weekly repeated for 4 weeks (hereinafter as the repeated administration). The initial dose, 10 mg/m2(ln), was escalated to 35 mg/m2(3.5n) in single administration and to 30 mg/m2(3n) in the repeated administration. A total of 35 cases were eligible for evaluation, consisting of 18 cases in single administration group and 17 in the repeated group. Both of single and repeated administration caused leukopenia dose-dependently, and the dose limiting toxicity (DLT) was judged as leukopenia. The maximum tolerated dose (MTD) was 30 mg/m2 in single administration and 25 mg/m2 in the repeated administration provided that administration is made weekly for 4 consecutive weeks. As subjective and objective adverse effects, general fatigue, anorexia, constipation, phlebitis etc. were observed, but all of these symptoms were relatively mild and recoverable. Peripheral neuropathy were found in two cases and judged as Grade 1. In this phase I study, a tendency of the decrease in tumor size was seen in 3 cases; 2 of non-small cell lung cancer and 1 of breast cancer. The pharmacokinetics of KW-2307 in blood after single administration showed a triphasic disappearance pattern with half-life of about 20 to 60 hrs. The data of pharmacokinetics after repeated administration revealed no accumulation of this agent. The recommended dose for early phase II study was supposed to be 20 to 25 mg/m2/week.

Adult↗

PubMed1994

[Vibratory perception threshold in normal volunteers].

A feasibility study on the vibratory perception threshold (VPT) in normal volunteers was conducted to detect anti-cancer drug induced peripheral neuropathy. The VPT was found to increase with age. The mean VPT in the main hand in 25 normal volunteers was significantly higher than in the other hand. No variation of VPT was observed in one day or one week. Variation of VPT in the lower extremities was detected between two examiners. In conclusion, the measurement of VPT was expected to be useful for the detection of anti-cancer drug induced peripheral neuropathy, if there is one examiner and the examined hand is specified.

Adult↗

PubMed1993

Lung cancer incidence rate for male ex-smokers according to age at cessation of smoking.

Lung cancer incidence rate after the cessation of smoking was assessed for male ex-smokers according to the age at cessation, using the results from a case-control study for ex-smoker versus continuing smoker, and the lung cancer incidence rate function for continuing smoker estimated from Japan Vital Statistics and the "Six-prefectural Cohort Study" in Japan. This hospital-based case-control study consisted of 776 lung cancer cases (553 current smokers and 223 ex-smokers) and 772 controls (490 current smokers and 282 ex-smokers) who started smoking at ages 18-22. The odds ratio of developing lung cancer for ex-smokers compared to continuing smokers according to years since the cessation of smoking was estimated for four age groups (55-64, 60-69, 65-74 and 70-79). Given that the number of years since cessation of smoking is the same, reduction of the odds ratio appeared to be greater for the younger age group than for the older age group, reflecting the shorter period of exposure for the younger age group. Lung cancer incidence rate (per 100,000) was assumed to be expressed by the following function; 1.7 x 10(-5) x (age -24.3) for continuing smokers and 0.15 x 10(-5) x (age) for nonsmokers. Lung cancer incidence rate among ex-smokers according to years since cessation was then estimated to be the above function multiplied by the odds ratio from the case-control study for each age group. In contrast to the greater reduction of the odds ratio among younger ex-smokers, reduction of the incidence rate, in terms of rate difference, was considerably greater for older ex-smokers due to a high incidence rate of lung cancer for older continuing smokers. This indicates that the absolute magnitude of reduction of the lung cancer incidence rate after cessation of smoking is greater for older ex-smokers, although the relative magnitude of reduction is greater for younger ex-smokers.

Age Factors↗

PubMed1993

Photodynamic therapy for cancers: a clinical trial of porfimer sodium in Japan.

Photodynamic therapy utilizing Photofrin has proven to be an effective modality that can be used in the treatment of a wide variety of solid tumors and luminal cancers. An argon pumped dye laser or excimer dye laser was used to deliver 630 nm light via quartz fibers passed through the biopsy channel subsequent to i.v. injection of photosensitizer. In this study, 64 patients with superficial cancers were treated in this manner but only 58 patients, including 21 with roentgenographically occult lung cancer, 8 with stage I lung cancer, 5 with esophageal cancer, 12 with gastric cancer, 8 with cervical cancer and 4 with bladder cancer were evaluable. Complete remission was obtained in 48 out of 58 cases (82.8%). There was no serious complication except skin photosensitivity, which was seen in 13 patients. We conclude that photodynamic therapy is efficacious in the treatment of superficial cancers where complete remission may be achieved.

Adult↗

PubMed1993

A prospective phase II study on photodynamic therapy with photofrin II for centrally located early-stage lung cancer. The Japan Lung Cancer Photodynamic Therapy Study Group.

PURPOSE: A phase II study was conducted between June 1989 and February 1992 to evaluate the activity and toxicity of photodynamic therapy (PDT) with photofrin II in centrally located early-stage lung cancer and to determine the complete response (CR) rate as the primary end point. PATIENTS AND METHODS: Patients had histologically proven lung cancer and endoscopically superficial thickening or small protrusions. All lesions were located in subsegmental or larger bronchi. All patients had a performance status (PS) of 0 to 2 and arterial oxygen pressure tension (PaO2) > or = 60 mm Hg. No lymph node or distant metastases were present. All patients received photofrin II (2 mg/kg) intravenously 48 hours before PDT. Tumor lesions were superficially photoradiated by an argon dye laser or an excimer dye laser. RESULTS: Of 54 patients with 64 carcinomas, 51 with 61 carcinomas were eligible for toxicity evaluation and 49 with 59 carcinomas were assessable for response. Of the 59 assessable carcinomas, 50 (84.8%; 95% confidence interval, 73.0% to 92.8%) showed a CR after initial PDT. The median duration of CR was 14.0+ months (range, 2.0+ to 32.4+). The multiple regression model indicates that estimated length of longitudinal tumor extent was the only independent prognostic factor for CR (P = .002). Five carcinomas that had a CR had a local recurrence at 6, 10, 12, 16, and 18 months after initial PDT, respectively. Toxicity assessment (World Health Organization [WHO] grade 2) showed transient elevation of ALT (1.9%), pulmonary toxicity (7.7%), and allergic reaction (7.7%), as well as sunburn (1.9%). CONCLUSION: PDT with photofrin II has an excellent effect on patients with centrally located early-stage lung cancer who have limited tumor invasion extending over a small area (< or = 1 cm).

Aged↗

PubMed1993

[Chemotherapy for small cell lung cancer].

This paper describes the results of a randomized trial comparing alternating chemotherapy with standard chemotherapy and of a trial of dose intensive chemotherapy with or without recombinant human granulocyte-colony stimulating factor (G-CSF) in small cell lung cancer (SCLC). 1) Between April 1985 and May 1988, the Japan Clinical Oncology Group conducted a randomized phase III trial of cyclophosphamide, doxorubicin and vincristine (CAV) versus cisplatin and etoposide (PE) versus CAV alternating with PE (CAV/PE). Three hundred patients were entered in the study, and 288 of them were eligible for analysis. The response rates for PE (78%) and CAV/PE (76%) were significantly higher than the rate for CAV (55%) (p < 0.01). The median survival time (MST) with CAV/PE (11.8 months) was superior to that with CAV (9.9 months) (p = 0.027) or that with PE (9.9 months) (p = 0.056); however, the survival advantage of CAV/PE disappeared when the data were adjusted for prognostic factors. These results have shown that CAB/PE is a reasonable approach for the management of SCLC. 2) Between May 1989 and September 1991, we carried out a randomized study to determine whether the dose intensity of the weekly CODE (cyclophosphamide, Oncovin, doxorubicin and etoposide) chemotherapy could be increased by the addition of G-CSF support. Sixty-three patients were entered in this study. The use of G-CSF was associated with a reduced incidence of neutropenic fever and an increase in the dose intensity. The MST for the patients treated with CODE plus G-CSF (58 weeks) was significantly longer than that for the patients treated with CODE alone (36 weeks). The results of this study showed that dose intensive weekly chemotherapy may improve the outcome of patients with ED-SCLC.

Aged↗

PubMed1993

[Radiotherapy and chemotherapy for locally advanced non-small-cell lung cancer: report of a clinical trial and review of the literature. South Osaka Lung Cancer Chemotherapy Study Group].

A prospective nonrandomized phase II trial was performed from June 1989 to Oct 1990 using concurrent chemotherapy and split course radiotherapy in the treatment of inoperable, locally advanced non-small-cell lung cancer (NSCLC). Eligibility criteria consisted of NSCLC, inoperable stage IIIA or IIIB excluding T3N0 or T3N1 of TNM classification, with pleural effusion, age 75 y.o. or less, PS0-2, with measurable lesion, previously untreated, normal bone marrow, adequate renal and hepatic function, PaO2 > or = 70 torr, and with no other active neoplastic disease. Patients were treated with 50 Gy of radiation in 25 fractions to the chest, together with 100 mg/m2 cisplatin and 8 mg/m2 mitomycin-C on day 1 and 29 and vindesine 3 mg/m2 on days 1, 8, 29, 36. Sixty-five patients were entered into this trial and 61 were eligible. There were 4 ineligible patients (1 stage II, 2 stage IV, 1 malignant lymphoma). Fifty-seven patients received 2 or more courses of chemotherapy, with dose modification in 42 patients. Only 5 patients received less than 50 Gy radiation dose. Fifty-three patients had a partial response for an overall response rate of 87% (95% CI 78-95%). Median duration of response was 276 days. Median survival time (MST) was 450 days. One, 2, and 3 year survival were 60%, 37%, and 28%, respectively. In IIIa (13 patients), MST was 358 days and 1, 2, and 3 year survival were 50%, 50%, and 42%, respectively. In IIIB (48%), MST was 450 days and 1, 2, and 3 year survival were 63%, 33%, and 25%, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenocarcinoma↗

PubMed1993

[Double blind controlled study of ubenimex (Bestatin) against squamous cell lung cancer--a multicenter cooperative study].

To investigate effects of the combination of ubenimex, chemotherapy, and radiotherapy against unresectable advanced squamous cell carcinoma of the lung, a placebo controlled double-blind study was performed. Of 365 registered cases, there were 258 cases in the complete radiation group in which the treatment as specified in the protocol (irradiation of 40 Gy or more to the thorax subsequent to chemotherapy) was conducted; the 50% survival time was 449 days and 363 days in the ubenimex group and the placebo group, respectively. A significant (p = 0.0473) prolongation of the survival time was noted in the ubenimex group, and the response rate was 60.9% and 50.0% (p = 0.087). From these results it was confirmed that ubenimex, when used in combination with chemotherapy and radiotherapy, not only enhances the tumor-reducing effect but also prolongs the survival time.

Aged↗

PubMed1993

[Photodynamic therapy (PDT) in roentgenographically occult lung cancer by photofrin II and excimer dye laser].

UNLABELLED: Patients (pts) with hilar type early lung cancer from 5 hospitals served as the subjects to assess the complete response rate and toxicity of PDT with Photofrin II (PHE) and excimer dye laser (PDT EDL-1). ENTRY CRITERIA: 1. Histologically proven lung cancer with endoscopically superficial thickening or small protrusion. 2. All lesions that were located proximally from the subsegmental bronchus, were visible to the distal margin of the lesions. 3. N0M0. METHOD: All pts received PHE (2 mg/kg) i.v., 48 hours before PDT. Tumor lesions superficially photoradiated by an excimer dye laser via flexible bronchoscope. RESULTS: From September 1990 to March 1992, 39 pts with 46 carcinomas (CA) were enrolled. Thirty-three pts with 40 CA were evaluable. 1. RESPONSE: Thirty-five in 40 CA showed a complete response (CR) (87.5%, 95% confidence limit: 73.2-95.8%). All 32 cases of CA equal to or less than 1 cm of tumor length were CR, but 3 CA relapsed locally. Thirty-three of 35 CA visible to the distal margin were CR (91.7%, 95% confidence limit: 77.5-98.3%). 2. Toxicity (> WHO grade 2): Three pts (7.7%) had transient dermatitis and sunburn, while another pt (2.6%) had symptoms due to obstructive pneumonitis. CONCLUSIONS: Tumors equal to or less than 1 cm in length and visible to the distal margin are curable by PDT.

Aged↗