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Biomedical subjects

K Furuse

Publications and source records attributed to K Furuse.

At least 19 recordsLinked to original sources

[Photodynamic therapy of centrally located early-stage lung cancer].

Photodynamic therapy (PDT) with photofrin II and excimer dye laser has an excellent effect on patients (pts) with centrally located early-stage lung cancer with a limited tumor length of 1 cm or less and a clearly visible tumor margin. Further, to expand the therapeutic area of PDT to these early-stage lung cancers, it is necessary to exploit more powerful laser equipment and more sensitive sensitizers. Also, it is essential in the decision to treat early-stage lung cancer to evaluate whether PDT can be used as an effective alternative therapy to surgery in patients with operable centrally located early-stage lung cancer. Finally, it is an important issue for the treatment of centrally located early-stage lung cancer to determine which therapeutic modalities have to be selected as the initial choice in endoscopic therapy.

Antineoplastic Agents

Relationship between associations of NOR and chromosomal anomalies in the abnormal embryos of nonobese diabetic and STZ-diabetic mouse.

Associations of nucleolar organizing regions (NORs) in the postimplantation stage embryos of nonobese diabetic (NOD) mice, and diabetic ICR mice induced by streptozotocin (ST), were studied to investigate the possible cause of the numerical anomalies of the chromosomes in their abnormal embryos. The incidence of NOR associations in abnormal embryos from diabetic NOD (NOD-DM) and STZ-diabetic mice was 11.7 and 7.7%, respectively. This incidence was significantly higher than that (1.2%, p < 0.05) of normal embryos from ICR mice which were used as control. From the results analyzed cytogenetically it was suggested that the higher incidence of chromosomal numerical anomalies in the embryos from NOD-DM and STZ-diabetic mice were caused by the chromosomal nondisjunction induced by associations of NORs. Furthermore, it was suggested that NOD-DM embryos have a tendency to increase the associations of NOR in a diabetic condition together with other factors such as autoimmune disease, however a diabetic condition alone induced chromosomal anomalies. Regarding relationships between the incidence of associations of NOR and the types of malformed embryos, it was also clear that all of the abnormal embryos from NOD-DM and STZ-diabetic mice had a high incidence of associations of NOR, and that the incidence was not related to the types of congenital anomalies. Furthermore, in the mal-developed tissue of embryos from STZ-diabetic mice, many chromosomal anomalies were found (26.6%), and the incidence was similar to that of whole embryos (22.6%).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Phase II study of concurrent radiotherapy and chemotherapy for unresectable stage III non-small-cell lung cancer. Southern Osaka Lung Cancer Study Group.

PURPOSE: To evaluate the response rate, toxicity, and 2-year survival rate of concurrent radiotherapy and chemotherapy for unresectable stage III non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Between July 1989 and October 1990, 65 patients with histologically or cytologically proven unresectable stage III NSCLC without T3N0-1M0 disease were entered onto this study. Sixty-one patients were eligible for response, survival, and toxicity analysis. Chemotherapy consisted of vindesine (3 mg/m2 on days 1, 8, 29, and 36), cisplatin (100 mg/m2 on days 1 and 29), and mitomycin (8 mg/m2 on days 1 and 29). Radiotherapy was administered for 3 weeks (2 Gy given 13 times, five fractions per week), followed by 10-day rest periods and then the previous schedule of radiotherapy repeated for 3 weeks. RESULTS: Of 61 eligible patients, 53 (86.9%) had a partial response (PR). The median response duration was 39.1 weeks (range, 8.4 to 163+). The median survival time was 16 months and the 2-year survival rate was 36.7%. Of 53 responding patients, 10 (16.4%) are alive and disease-free after 2 years. The major toxicity was leukopenia (> or = grade 3, 95%). Other toxicities of > or = grade 3 included thrombocytopenia (45%), anemia (28%), nausea/vomiting (16%), fever (11%), and esophagitis (6%). Treatment-related death occurred in two patients. One patient died of pulmonary toxicity (interstitial pneumonitis) and the other of esophagobronchial fistula with pulmonary infection. CONCLUSION: Concurrent radiotherapy plus chemotherapy with mitomycin, vindesine, and cisplatin (MVP) can be safely administered to patients with stage III NSCLC, with excellent response rates and 2-year survival rates.

Adult

[Phase III study].

After a drug is found to have some minimal amount of activity in phase II study, the next step is to determine the effectiveness of compared new treatment to no-treatment or placebo, the best current standard therapy, and toxicity in phase III study. Phase III study is the most rigorous and extensive type of scientific clinical investigation of a new treatment. Accordingly, much of this issue is devoted to the principles of phase III study.

Antineoplastic Agents

[Late phase II trial of RP56976 (Docetaxel) in patients with non-small-cell lung cancer].

A late phase II trial on RP 56976 (Docetaxel) was carried out against stage IIIB or IV non-resectable non-small cell lung cancer as a multicenter cooperative trial. Of 78 enrolled patients, seventy five patients were eligible and 71 were evaluable for the response. The overall response rate was 19.7% (14/71): 27.9% (12/48) of patients with adenocarcinoma and 10.0% (2/20) of patients with squamous cell carcinoma responded to docetaxel. The response rate was 15.0% (3/20) in patients with stage III B disease and 21.6% (11/51) in patients with stage IV disease. Leukopenia (neutropenia) occurred frequently, but most tended to recover in a short period of time. Other adverse reactions included nausea/vomiting, anorexia, general malaise, alopecia, all of which were not severe. Severe hypersensitivity reactions occurred in 2 patients (2.7%). The results seemed to show usefulness of docetaxel for the treatment of patients with non-small cell lung cancer.

Adenocarcinoma

[A late phase-II trial comparing KW-2307 with vindesine in non-small cell lung cancer (1). Lung cancer section in KW-2307 Study Group].

A multicenter cooperative study was performed to compare KW-2307 (KW), a novel vinca alkaloid (VA) derivative, and vindesine (VDS), with respect to tumor response and toxicity in patients (pts) with non-small cell lung cancer. In the former part of the trial, pts received monotherapy with KW 25 mg/m2 or VDS 3 mg/m2. Pts refractory to treatment with KW or VDS were crossed over to treatment with VDS (3 mg/m2/W x 3) or KW (20 mg/m2/W x 3), respectively, in combination with cisplatin (CDDP) 80 mg/m2. Both drugs were administered in 4 courses or more once weekly by intravenous bolus injection in monotherapy. In the subsequent combination therapy, non-responders were treated with CDDP on day 1 and KW or VDS on day 1, 8 and 15 with a course of 28 days, and treatment was given in 2 courses or more in principle. According to the method of O'Brien/Fleming, comparison of tumor response between the 2 treatment groups in the 2nd stage was performed in 154 cases. The response rate of KW group (29.4%, 22/75) was significantly better than that of VDS group (9.3%, 7/75). The main adverse effect in both groups was leukopenia (neutropenia), and no significant difference was observed between the incidence in each group. Among other adverse effects, increased GOT, fever and phlebitis were slightly more often found in KW group, and alopecia and paresthesia a little more in the VDS group. In the later part of combination therapy with CD DP, the KW group achieved PR in 10 of 34 pts (29.4%), and no response was observed in the VDS group (28 pts).

Adenocarcinoma

A phase II study of vinorelbine, a new derivative of vinca alkaloid, for previously untreated advanced non-small cell lung cancer. Japan Vinorelbine Lung Cancer Study Group.

To evaluate the effectiveness of vinorelbine (NVB) in patients with non-small cell lung cancer (NSCLC), a late Phase II study was conducted. A total of 80 patients with Stage III or IV NSCLC who had no previous therapy were entered into the study. Seventy-nine patients were eligible for response and toxicity. NVB was administered weekly by intravenous injection at a dose of 25 mg/m2 in 20 ml of saline and was generally administered in four cycles or more, unless patients had disease progression. Of the 79 eligible patients, 23 (29.1%) showed a partial response (95% confidence interval, 19.1-40.4%). The median duration of partial responses was 14.7+ weeks. The median survival time for all patients was 40.1+ weeks. The major toxicity was leukopenia. Grade 3 and 4 leukopenia occurred in 48 patients (60.8%). Other toxicities of grade 3 or more included anemia (6.3%), local cutaneous reaction (3.8%), pneumonitis (1.3%), nausea and vomiting (1.3%), mucositis (1.3%) and constipation (1.3%). The absolute dose-intensity of NVB was 22.33 mg/m2/week. A weekly schedule of intravenous administration of 25 mg/m2/week of NVB was reasonable for maintenance of activity, and acceptable for toxicity in the chemotherapy of advanced NSCLC.

Adult

Case-control study for lung cancer and cigarette smoking in Osaka, Japan: comparison with the results from Western Europe.

In order to clarify the relation between cigarette smoking and lung cancer, a case-control study was conducted. The case series consisted of 1,376 lung cancer patients (1,082 males and 294 females) who were newly diagnosed and admitted to eight hospitals in Osaka during 1986-88. Smoking histories were compared with those of 2,230 controls (1,141 males and 1,089 females) admitted to the same hospitals during the same period without established smoking-related diseases. Odds ratios of current smoker versus nonsmoker were 18.1, 1.9, 21.4, and 3.8 for squamous, adeno, small, and large cell carcinoma, respectively, for males, and 9.7, 1.3, 12.1, 3.7, respectively, for females. Compared to the results from previous studies in Japan, the magnitude of the odds ratios for squamous and small cell carcinoma is approaching the level of Western Europe in the late 1970s. Population attributable risk of exsmokers has also been increasing to the level of Western Europe. Among male current smokers, smoking intensity, such as number of cigarettes per day or fraction smoked per cigarette, seemed to have a slightly greater influence on squamous cell carcinoma than adenocarcinoma, while factors associated with the spread of cigarette smoke, such as inhalation, seemed to have greater influence on adenocarcinoma. The difference in the distribution of these smoking characteristics between Japan and Western Europe could not fully explain the difference in lung cancer incidence and distribution of histologic types between the two areas.

Adenocarcinoma

Role of radiotherapy in combined modality treatment of locally advanced non-small-cell lung cancer.

PURPOSE: For patients with locally advanced (stage III) non-small-cell lung cancer (NSCLC), radiotherapy (RT) has been used conventionally for many years. Few prospective trials have determined the role of RT. Recently, chemotherapy (CT) has been shown to produce excellent responses in regionally advanced disease. We therefore conducted a randomized trial using cisplatin (P)-based CT regimens with or without thoracic irradiation. PATIENTS AND METHODS: We randomly assigned 92 patients with locally advanced NSCLC to receive one of three arms of P-based combination chemotherapy: vindesine (V) plus P, mitomycin (M) plus V plus P, or etoposide (E) plus P alternating with V plus M. After two cycles of CT, patients were reevaluated and those with stage III were again randomized to receive RT or not. RT consisted of 50 to 60 Gy in 5 to 6 weeks; 2 Gy was delivered once daily in conventional fractions. RESULTS: Sixty-three patients were included in the second randomization. The patients in the CT/RT group (n = 32) and CT-alone group (n = 31) were comparable in terms of age, sex, performance status, histologic features, stage of disease, and induction CT regimen. The median durations of survival were similar for the two groups (461 days in CT/RT group and 447 days in CT-alone group). The survival rate in the CT/RT group was 58% at 1 year, 36% at 2 years, and 29% at 3 years, as compared with 66%, 9%, and 3% at 1, 2, and 3 years, respectively, in the CT-alone group. One patient in the CT/RT group died of pneumonitis, but there were no CT-related deaths. CONCLUSION: In locally advanced NSCLC, P-based combination CT followed by chest irradiation significantly increases the number of long-term survivors as compared with CT alone. RT to bulky disease in the thorax is thus an important part of combined modality therapy, and a necessary part of further studies in locally advanced disease.

Antineoplastic Combined Chemotherapy Protocols

Efficacy of a new 5-fluorouracil derivative, BOF-A2, in advanced non-small cell lung cancer. A multi-center phase II study.

Oral BOF-A2 (Emitefur), a new derivative of 5-fluorouracil (5-FU) containing both 1-ethoxymethyl-5-FU (EMFU), a masked form of 5-FU, and 3-cyano-2,6-dihydroxypyridine (CNDP), an inhibitor of 5-FU degradation, was administered to 71 non-small cell lung cancer (NSCLC) patients in a multi-center phase II study. The patients were scheduled to receive at least 2 courses of treatment, each consisting of 200 mg twice daily for 2 weeks followed by a 2-week rest period. Out of 62 evaluable patients, 11 (18%) responded (8 of 44 adeno- and 3 of 15 squamous cell carcinomas). Thirty-four patients showed no change and 17 progressive disease. The incidences of grade > or = 2 hematologic toxicity were 5-8% for leukopenia, thrombocytopenia, and anemia. The incidences of non-hematologic toxicity of grade > or = 2, such as anorexia, nausea/vomiting, and diarrhea, were close to 20% or lower.

Adenocarcinoma

[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

[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

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

[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

[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

[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