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Biomedical subjects

H Niitani

Publications and source records attributed to H Niitani.

At least 73 records · Page 4Linked to original sources
PubMed1994

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↗
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

[Early phase II clinical study of RP56976 (docetaxel) in patients with primary pulmonary cancer. Docetaxel Cooperative Study Group for Lung Cancer].

An early phase II clinical study of RP56976 (Docetaxel), a new anticancer agent of plant origin, was conducted in patients with primary pulmonary cancer as a multicentered study involving 28 Japanese institutions. Docetaxel was administered at an intravenous dose of 60 mg/m2 based on the results of a phase I clinical study, and efficacy and safety were examined. Of the 65 patients enrolled, 57 patients were evaluated to have completed the scheduled course of treatment by the Evaluation Committee. The antitumor effect in patients with non-small cell lung cancer was 21.4% (9/42). In patients not previously treated, the antitumor effect was 30.0% (6/20), in patients previously treated the antitumor effect was 13.6% (3/22), and in 13.3% (2/15) of patients with small cell lung cancer. This shows that docetaxel had an efficacy for non-small cell lung cancer. Hematological adverse reactions included leukopenia and neutropenia of Grade III or more as specified in the Adverse Event Reporting Form proposed by the Japan Society for Cancer Therapy in 53.3% (32/60) and 78.3% (47/60) patients, respectively. Other major adverse reactions included alopecia and anorexia. Neurological symptoms developed at a low frequency and were mild in severity.

Adult↗
PubMed1994

[Late phase II clinical study of RP56976 (docetaxel) in patients with non-small cell lung cancer].

A late phase II clinical study of RP56976 (Docetaxel) was conducted in patients with non-small cell lung cancer. Patients with non-small cell lung cancer in Stage IIIB and Stage IV not previously treated were enrolled. Docetaxel was administered at a dose of 60 mg/m2 based on the results of a phase I and an early phase II clinical study, and the efficacy and safety were examined. Of the 77 patients enrolled, 72 patients were evaluated to have completed the scheduled course of treatment by the Evaluation Committee. A partial response (PR) was seen in 18 patients, and the overall response rate was 25.0%. The response rate classified by clinical stage was 28.0% (7/25) in patients with Stage IIIB and 23.4% (11/47) in patients with Stage IV. Hematological adverse reactions included leukopenia of Grade III or more in 53.3% (40/75) and neutropenia of Grade III or more in 86.7% (65/75) as specified in the Adverse Event Reporting Form proposed by the Japan Society for Cancer Therapy. Other major adverse reactions included alopecia, asthenia, and fever, all of which were tolerable. From these results, the efficacy of docetaxel for the treatment of non-small cell lung cancer was confirmed.

Adolescent↗
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

[Small cell lung cancer].

Explore the source record for details and available documents.

Antineoplastic Combined Chemotherapy Protocols↗
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

[Study of cardiac function in first stage examination of RA-700. RA-700 Clinical Study Group].

There are many studies in the literature on the subject of anti-neoplastic drugs for acute and chronic cardiac toxic function. It is important to check previously the cardiac toxicity of the new anti-neoplastic drugs. Now we have had a chance to study the first stage examination of RA-700, isolated from Rubia akane or Rubia cordifolia. Then we tried to study several kinds of parameters, for instance ECG, ultrasonic cardiograms and arterio-grams on cardiac toxicities of RA-700. We injected the first group of neoplastic patients only once with RA-700, while in the second group, we injected them with RA-700 for 5 consecutive days (see our previous report.) In the present study, we made some conclusions about the administration of RA-700. 1) Changes in cardiac function were noted in both groups. 2) Changes in blood pressure, sigma QRS, ejection fraction, and fractional shortening of the second group tended to be more extreme than those of the first group. Care for continuity is a concern with long-term and high doses of RA-700. 3) Because of the small sample, we could find no relationship between the changes in cardiac function and the injection doses of RA-700. 4) Therefore, the cardiac function must be checked by giving anti-neoplastic drugs to neoplastic patients.

Adult↗
PubMed1993

[Antimicrotubule agents].

Microtubules are among the most strategic subcellular targets of anticancer agents. Recently, new antimicrotubule agents have been introduced to clinical cancer chemotherapy. Navelbine is a new derivative of vinca alkaloids, which especially has an activity against NSCLC. Unlike classical anti-microtubules agents like colchitine and vinca alkaloids, which induce depolymerization of microtubules, taxol has an unique mechanism of action which induces tubulin polymerization. Taxotere, an analogue of taxol is slightly more active as a promoter of tubulin polymerization than Taxol. E7010 is a novel sulfonamide that inhibits tubulin polymerization. Results of preclinical and clinical studies of these agents are reviewed.

Aminophenols↗
PubMed1993

[Severity and distribution of patchy white matter lesions in healthy individuals].

We performed MRI on 57 socially active, healthy people without neurologic signs or symptoms when admitted to our hospital for a routine medical evaluation. Of these, 34 persons had patchy white matter lesions (PWMLs). Mild lesions were distributed mainly around the anterior horns or the bodies of the lateral ventricles. However, more severe lesions were distributed widely, involving both the anterior halves of the brains and the regions around the posterior horns. The mean total and LDL cholesterol levels were higher in healthy individuals with PWMLs than in those without them. No other significant difference between the groups was found.

Adult↗
PubMed1993

[DNA topoisomerase inhibitor].

DNA topoisomerases are enzymes involved in various aspects of genetic processes by catalyzing a topological change of DNA. Topoisomerase is now viewed as an important cellular target of antitumor drugs. These drugs targeting topoisomerase have been used to establish a relationship between drug-induced cleavable complex formation and cytotoxicity. Topoisomerase I is shown to be the cellular target of camptothecin and its derivatives. And topoisomerase II targeting drugs are both intercalative drugs (acridines, ellipticines, anthracyclines) and non-intercalative drugs (epipodophyllotoxin derivatives). And then Irinotecan, topotecan, sobuzoxane and IST-622 are unique topoisomerase inhibitors and are under investigation in Japan, the new antitumor drugs targeting topoisomerases are reviewed.

Antineoplastic Agents↗
PubMed1993

[An early phase II trial combining cisplatin and carboplatin in advanced non-small cell lung cancer].

We conducted an early phase II trial in advanced non-small cell lung cancer (NSCLC) to evaluate response efficacy of a combination of Cisplatin (CDDP) and Carboplatin (CBDCA). The twenty-six patients in the study had had no previous treatment. They received a sequential administration of 300 mg/m2 CBDCA and 80 mg/m2 CDDP with approximately 3,500 ml of hydration on day 1 every 4 weeks. All patients were evaluable for response and toxicity. Ten (38.5%) of all assessable patients achieved a partial response (95% confidence interval, 19.8-57.2%). Response rates for patients with stage III A, III B and IV- disease were 40.0 (2/5), 70.0 (7/10) and 9.1% (1/11), respectively. Response rates for patients with squamous cell carcinoma, adenocarcinoma and large cell carcinoma were 35.7 (5/14), 45.5 (5/11) and 0.0% (0/1), respectively. The median survival time (MST) of all patients was 11 months. The MST for patients with stage III disease was 14 months; for those with stage IV disease it was 7 months. The MST for responding patients was 15 months and for not responding patients 5 months. Major toxicities were hematologic and gastrointestinal, and the dose-limiting factor was thrombocytopenia. This combination chemotherapy was effective against NSCLC with tolerable toxicities. Further trials are warranted to determine the efficacy of the combination chemotherapy.

Adult↗
PubMed1993

[Clinical evaluation of granisetron for nausea and vomiting induced by anticancer drugs--optimal dose-finding study].

The efficacy, safety and usefulness of oral granisetron for nausea and vomiting induced by the administration of anticancer drugs were compared among four doses using the subjects registered through telephone calls by the physicians-in-charge. The clinical efficacy of the drug was assessed as "remarkably effective" or "effective" in 50.0% (11/22) in the 0.5 mg group. 68.4% (13/19) in the 1 mg group, 81.0% (17/21) in the 2 mg group and 78.3% (18/23) in the 4 mg group. The antiemetic effect of the drug persisted for approximately 24 hours in the 2 mg and 4 mg groups. No adverse event or abnormal laboratory value fluctuation which might pose a clinical problem was observed. From these results, single administration of oral granisetron at a dose of 2 mg once a day was considered to be the optimal administration and dosage for nausea and vomiting induced by the administration of anticancer drugs.

Administration, Oral↗