Biomedical subjects

T Mukaiyama

Publications and source records attributed to T Mukaiyama.

At least 37 records · Page 2Linked to original sources

PubMed1994

[Phase I study of paclitaxel].

Paclitaxel, a novel antimicrotubule agent that enhances tubulin polymerization and microtubule stability, was administered as a 24-hour infusion in a phase I study. Twelve patients received 32 courses at 50, 100, 150, and 200 mg/m2. A premedication regimen of dexamethasone, diphenhydramine, and ranitidine was used to prevent the acute hypersensitivity reactions (HSRs). The dose-limiting factor was leukopenia (granulocytopenia) associated with Grade 4 infection. The maximum tolerated dose was 200 mg/m2. Other non-hematological effects included peripheral neuropathy, myalgia, alopecia, and elevations of transaminase and alkaline phosphatase. Severe HSRs were not observed. The paclitaxel plasma concentration declined with a half-life of 10.0 to 24.9 hours. Excretion into urine within 72 hours was in the range of 7.28 to 11.34% of paclitaxel dosage. Two patients with breast cancer at the 200 mg/m2 dose level had partial responses. The recommended dose of paclitaxel for phase II study, when administered as a 24-hour infusion, is considered to be 150 mg/m2 every 3 weeks.

Adolescent↗

PubMed1992

[High-dose thio-TEPA with escalating doses of epirubicin and autologous hematopoietic stem cell transplant for refractory cancers].

We studied high-dose chemotherapy with autologous hematopoietic stem cell transplant for patients (pts) with non-Hodgkin's lymphoma (NHL) and breast cancer (BC) refractory to conventional therapies. The conditioning regimen consisted of thio-TEPA 6 mg/kg/day for 3 consecutive days with escalating doses of epirubicin (EPI) in dose steps of 120, 150, 180 and 210 mg/m2 on day 1. Mucositis was dose limiting toxicity at 210 mg/m2 on this regimen, and the recommended dose of EPI was judged to be 180 mg/m2. No cardiotoxicities were observed. There were 3 with complete responses (CR), one partial response (PR) in pts with NHL, 3CR and 5PR in pts with BC. The median duration of response was 8 months (mos) and 4 mos, respectively. Hematological recovery was significantly earlier in the pts receiving both autologous bone marrow transplant (ABMT) and peripheral blood stem cell transplant (PBSCT) than ABMT alone. This approach made it possible to overcome the prolonged PLT recovery, which was one of the major problems on ABMT.

Adolescent↗

PubMed1992

[Phase I and pharmacokinetic study of SM-5887 by 5-day schedule].

Pharmacokinetics of SM-5887, a new totally synthetic anthracycline derivative, was studied in a phase I setting by 5-day schedule. The maximum tolerated dose was 25 mg/m2/d (total dose: 125 mg/m2/body) and the dose-limiting toxicity was myelosuppression which was consistent with the results of the phase I study by a single dose. In terms of subjective side effects, decreased nausea/vomiting and increased stomatitis were observed. In pharmacokinetic study, AUC of active form of SM-5887 increased on day 5 compared to that day 1. This result suggested that 5-day schedule of SM-5887 produced an accumulation of the active form. Five-day treatment schedule of SM-5887 seems to be more tolerable and further clinical study was recommended.

Adult↗

PubMed1991

Evaluation of prognostic factors for 233 patients with recurrent advanced breast cancer.

We analyzed possible prognostic factors in 233 patients with recurrent advanced breast cancer treated primarily by adriamycin, cyclophosphamide and ftorafur (ACF) therapy and ACF modifications. The patients were in the Cancer Institute Hospital from 1977 to 1986, and were followed-up until 1989. In terms of chemotherapeutic response, complete and partial responses were observed in 31 (13%) and 100 (43%) patients, respectively. The overall median survival from the beginning of chemotherapy was 20.3 months. The factors evaluated were response to chemotherapy, performance status (PS), age, disease-free interval (DFI), menopausal status, number of metastatic sites (step classification), presence or absence of liver metastasis, presence or absence of malignant effusion, and presence or absence of prior radiotherapy. Out of the nine factors, response to chemotherapy, PS, age, DFI and liver metastasis were significant factors affecting survival in univariate analysis, and multivariate analysis of these five factors revealed the survival to be markedly affected by response to chemotherapy (P less than 0.00001), PS (P = 0.00001) and DFI (P less than 0.00001).

Adult↗

PubMed1991

[Combination chemotherapy of advanced Hodgkin's disease with vincristine, cyclophosphamide, procarbazine, and prednisolone].

Thirty-three patients with advanced Hodgkin's disease were treated with a combination chemotherapy consisting of vincristine 1 mg/m2 iv on day 1, 8, cyclophosphamide 500 mg/m2 iv on day 1, procarbazine 100 mg/m2 p.o. day 1-7, and prednisolone 40 mg/m2 p.o. day 1-7. Twenty patients received this regimen every 4 weeks (VCPP II regimen). Furthermore, we conducted higher dose intensive VCPP II-2 regimen which was repeated every two weeks for thirteen patients. Complete response rate of both regimens was 63% (VCPP II 45%, VCPP II-2 85%). The median duration of CR was 37 + months. Leukopenia, neurotoxicity and gastrointestinal toxicity were commonly observed but were clinically manageable. These results indicate that high dose intensive chemotherapy is effective for achieving high CR rate for advanced Hodgkin's disease.

Adolescent↗

PubMed1991

[Phase I-II study of hepatic intraarterial one-shot administration of adriamycin in patients with metastatic liver cancer].

For the purpose of obtaining the optimal dose of adriamycin (ADM) in hepatic intraarterial one-shot administration, phase I-II study was conducted in 14 patients with various liver cancers. The starting dose of ADM was 20 mg/m2 (4 patients) and the doses were escalated to 40 mg/m2 (5 patients), 60 mg/m2 (4 patients) and 80 mg/m2 (3 patients). One patient with salivary gland cancer showed PR for the liver metastasis. Major toxicity was leukopenia. With a dose of 40 mg/m2, 3 out of 4 patients showed nadir of WBC counts below 4,000/mm3 (2,400, 2,900, 3,100), 60 mg/m2 (1,100, 1,500, 2,200 and 2,700), and 80 mg/m2 (900, 1,200, and 1,400). Nadirs of WBC counts were observed from 9 to 15 days after the one-shot administration, and recovered above 4,000/mm3 in 1 to 3 weeks. Plasma concentrations of ADM from the peripheral vein were determined by HPLC in 12 patients, 14 courses. The curves of ADM plasma levels after 20 and 40 mg/m2 bolus injections were almost the same, and in patients treated with 60 and 80 mg/m2 the curves were also quite similar, but higher in the plasma levels, comparing with in patients with 20 and 40 mg/m2. There might be a limit of ADM tissue absorption, and above the doses 60 mg/m2, ADM might be overflowed, followed by side effects, especially leukopenia. Upon these data of venous plasma concentrations of ADM and leukopenia, the optimal dose of ADM in the hepatic intraarterial one-shot administration seemed to be 40 mg/m2.

Adult↗

PubMed1990

In vitro and in vivo release of soluble erbB-2 protein from human carcinoma cells.

An enzyme-linked immunosorbent assay (ELISA) was developed to measure soluble erbB-2 protein in culture supernatants of various human cell lines and sera of patients suffering from recurrent breast carcinoma. Soluble erbB-2 protein was demonstrated in culture supernatants of cell lines that expressed high levels of erbB-2 protein as shown by western blot analysis of cell lysates. Increased levels of the protein, 40- to 190-fold higher than in healthy controls, were demonstrated in sera of 3 out of 12 patients with breast carcinomas. On immunohistological study of tumor tissues from 9 patients, high immune reaction with the anti-erbB-2 protein antibody was observed in 2 cases. These were two of the three patients who had elevated levels of erbB-2 protein in serum (a sample was not available from the third patient). These results raise the possibility that soluble erbB-2 protein level in serum can be used as an indicator for spread of carcinomas that overexpress erbB-2 protein.

Adenocarcinoma↗

PubMed1990

Immunohistochemical evidence of the extracellular localization of calcium-activated neutral protease (CANP) in rabbit skeletal muscle, lung and aorta.

The subcellular localization of calcium-activated neutral protease requiring a millimolar calcium concentration (m-CANP) was examined by light and electron microscopy in various tissues of the rabbit, using an immunoperoxidase method with a monoclonal antibody (1C6D1). In skeletal muscles, specific staining for m-CANP was recognized on collagen fibrils (ca 40 nm in diameter) with a periodic banding pattern. In the lung, dense reaction products were precipitated on elastic fibers under the bronchial epithelia. In the aorta, tunica intima and adventitia were intensely stained. Dense reaction products were observed on collagen fibrils and elastic fibers. Basal laminae, on the other hand, were not stained by anti m-CANP antibody in these tissues. These findings suggest that m-CANP may be involved in the regulation of the structure and function of the extracellular matrix.

Animals↗

PubMed1990

[Autologous hematopoietic stem cell transplantation--application to recurrent breast cancer].

High-dose chemotherapy with autologous hematopoietic stem cell transplantation (HD-CT with AHSCT) has been studying to overcome drug resistance and to obtain higher antitumor efficacy on hematological malignancies and solid tumors. The annual rate of transplants is increasing steadily. This method has boon now performed safely owing to the development of researches about hematopoietic growth factors and stem cells. It was demonstrated that the administration of recombinant human granulocyte colony stimulating factor (rhG-CSF) and granulocyte Macrophage colony stimulating factor (rhGM-CSF) could shortened the duration of leukopenia. Autologous peripheral stem cell transplantation has the advantage for the earlier bone marrow reconstitution and the unnecessary of purging. Recently, it was found that rhG-CSF and rhGM-CSF could increase the number of peripheral blood stem cells, so further studies are expected. For recurrent breast cancers resistant to conventional chemotherapy, response rates of 60-80% may be achieved using HD-CT with AHSCT, but the duration of response is generally short. So, trials consisted of induction conventional chemotherapy followed by HD-CT with AHSCT in the earlier course of the illness have conducted to obtain higher complete response (CR) rate and survival rate. Although the observed duration is short, higher CR rate has been achieved in several clinical studies. There are still remaining with many problems to be settled, HD-CT with AHSCT may have the potentiality to cure not only recurrent breast cancer but also another malignancies.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1990

[High-dose cyclophosphamide, thio-TEPA, etoposide with autologous bone marrow transplantation for refractory cancers].

We studied high-dose chemotherapy with autologous bone marrow transplantation (ABMT) for 10 patients with malignant lymphoma or breast cancer refractory to conventional chemotherapy. Conditioning regimen was consisted of cyclophosphamide 60 mg/kg/day, thio-TEPA 6 mg/kg/day, Etoposide 500 or 600 mg/m2/day for 3 consecutive days. Of 9 patients with measurable lesions, there were 5 with complete responses (CR) and 4 with partial responses (PR). Severe bone marrow suppression, mucositis, and diarrhea were observed in all patients. Furthermore, biliary stasis, which was unpredictable side effect, was observed in most patients. So, mucositis and/or hepatotoxicity were thought to be the dose-limiting factors. But these were not life-threatening and clinically manageable. All patients were received recombinant human granulocyte colony stimulating factor (rhG-CSF) at a dose of 300 micrograms/m2/day and which was effective for shortening the duration of leukopenia. In vitro Colony Forming Unit-granulocyte macrophage assay (CFU-GM assay) showed a significant correlation between the ability of colony formation and the days to recovery of granulocytes.

Adult↗

PubMed1990

[Combination chemotherapy of ifosfamide, cisplatin and vindesine for non-small cell lung cancer].

Twenty patients with advanced non-small cell lung cancer were treated with a combination chemotherapy consisting of ifosfamide (IFX), cisplatin (CDDP) and vindesine (VDS). The treatment schedule was IFX 1.3 g/m2 i.v., on days 1-5, CDDP 20 mg/m2 i.v., on days 1-5, and VDS 3 mg/m2 i.v., on days 1 & 8, and, in principle, the regimen was repeated every 4 weeks. Of 19 evaluable patients, there were 1 CR, 7 PR, 10 NC and 1 PD, with an overall response rate of 42.1%. The median duration of responses was 7.45 months, and the median survival time of all patients was 13.2 months. The major toxicities occurring were hematologic toxicity, alopecia, gastrointestinal toxicity and peripheral neuropathy. Hematologic toxicity was severe and was judged to be dose limiting, but clinically manageable. These results indicate that this combination chemotherapy is active against non-small cell lung cancer and deserves further studies.

Adult↗

PubMed1990

[Treatment of cancer in the elderly--cancer chemotherapy].

A retrospective analysis was made of elderly cancer patients (pts) who were treated with cancer chemotherapy in our Department of the Cancer Inst. Hosp. There were 180 pts above age 70 years at the start of chemotherapy between July of 1974 and December of 1988. Characteristics of these 180 pts were as follows: (1) 73 years of age in median (70-89 years), (2) 67 pts with malignant lymphoma (37%); 40 with lung ca. (22%), 20 with breast ca. (11%), stomach ca., colorectal ca., multiple myeloma and other; (3) Combination chemotherapy given to 174 pts; (4) OUTCOME: 41 pts (23%) were alive as September of 1989, and autopsy performed in 66 out of 87 pts who died in the hospital (76%). There were no special chemotherapeutic regimens only for elderly pts. Intensity of adequate chemotherapy based on therapeutic protocols was evaluated, dividing pts into two groups: full-dose group and reduced-dose group. Most pts (96%) with small cell lung cancer (SCL) were treated on protocols. For example, 12 elderly pts with SCL were treated with VEC regimen (VCR.VP-16.CTX); eight pts with full-dose and four reduced-dose, and their response rate (CR/PR) of 50%/38% and 25%/75%, respectively, and in 23 younger pts; 20 full-dose and three reduced-dose, and response rate 35%/35% and 33%/33%, respectively. There were 40 pts with acute non-lymphocytic leukemia over 60 years old, treated at Jikei University and in our Department. CR rates of these pts according to age showed a lower percentage with advancing age. Elderly pts with malignancies responsive to chemotherapy should be treated with the same regimen used in younger pts. But doses of each drug have to be adjusted to organ functions of each pt. patients with unresponsive malignancies, must be enrolled in clinical trials, and their responses and toxicities evaluated by age-stratified analysis.

Aged↗

PubMed1990

[High-dose leucovorin and 5-fluorouracil in advanced gastric and colorectal cancer. High-Dose Leucovorin and 5-FU Study Group].

A multicenter cooperative study was conducted from June 1988 to July 1989 to evaluate the clinical efficacy of high-dose dl-Leucovorin (dl-LV) and 5-FU treatment in 61 cases of advanced gastric and colorectal cancer. The administration schedule was a 2-hour infusion of dl-LV (500 mg/m2) and an IV bolus of 5-FU (600 mg/m2), given 1 hour after the beginning of LV infusion. Patients (pts.) were treated q week x 6 then evaluated for response. Thirty one gastric cancer pts. were divided into two groups; nine pts. treated with 30 min. infusion of 5-FU, and the remaining 23 pts. treated with IV bolus. PR was obtained in 2/9 (22.2%) and in 7/22 (31.8%) of the first and second group, respectively. An overall response rate was 9/31 (29%). Thirty colorectal cancer pts. were divided the same: 13 pts. treated with 30 min. infusion of 5-FU and the remaining 17 pts. treated with IV bolus. PR was obtained in 2/13 (15.4%) and in 7/17 (41.2) of the first and second groups, respectively. An overall response rate was 9/30 (30%). Median survival time for the gastric cancer group was 9.4 months, and for the colorectal cancer group was 13.6 months. Toxicity was within acceptable limits. Toxic effects included diarrhea, stomatitis, anorexia and myelohypoplasia. Our data suggests that high dose LV and 5-FU seems to be a very promising combination and warrants a further investigation.

Adult↗

PubMed1990

[Antitumor activity of N-(5-indanylsulfonyl)-N'-(4-chlorophenyl)-urea, LY 186641 against various human cancers using subrenal capsule assay].

An analog of diarylsulfonylurea, LY 186641 has a broad spectrum activity against murine solid tumors including Colon 26 and LX-1. Preclinical evaluation of the anticancer activity of LY 186641 using the subrenal capsule assay was performed in fresh human tumor samples derived from 87 patients with various cancers and 70 (80%) samples were evaluable. The overall chemosensitivity rate of LY 186641 was 37% and the average tumor growth inhibition rates (TGIRs) of malignant lymphoma, esophageal cancer and colorectal cancer were 51 +/- 19%, 51 +/- 20% and 48 +/- 12%, respectively. The antitumor effect obtained by LY 186641 was comparable to that of the standard anticancer drugs including adriamycin, 5-fluorouracil and cisplatin evaluated in this assay simultaneously. Based upon these results, LY 186641 is considered to have antitumor activity against some human cancers.

Antineoplastic Agents↗

PubMed1989

Phase I and pharmacokinetic study of SM-5887, a new anthracycline derivative.

SM-5887, a new totally synthetic anthracycline derivative was studied in a phase I setting. Twenty-nine evaluable courses of treatment were conducted in groups at doses increasing from 10 to 130 mg/m2. Myelosuppression was the dose-limiting toxicity and a MTD was 130 mg/m2. At 130 mg/m2 the median lowest white blood cell count was 0.7 x 10(3)/cmm (range: 0.3-1.8) and the median lowest granulocyte count was 0.1 x 10(3)/cmm (range: 0-0.7) and the median lowest platelet count was 57 x 10(3)/cmm (range: 4-176). Non-hematologic side effects were mild gastrointestinal symptoms and hair loss. The recommended dose and schedule for phase II setting is 100 mg/m2 every 3 weeks.

Adult↗

PubMed1989

[Effect of recombinant human granulocyte colony stimulating factor (rhG-CSF) in patients receiving chemotherapy--phase I study].

Seventeen patients with advanced malignancy were treated with recombinant human granulocyte colony stimulating factor rhG-CSF (KRN 8601) infused intravenously over a period of 30 minutes once daily at the dose level/25 micrograms, 50 micrograms, 100 micrograms, 200 micrograms, 400 micrograms, 800 micrograms/m2 for 14 consecutive days, and the effect was compared to the period without rhG-CSF treatment. The maximum numbers of peripheral leukocyte (granulocyte) showed a dose-related increase and the nadir of leukocyte counts escalated with shortening of the period. After stopping infusion, the neutrophil count dropped to the base line level within two or three days. RhG-CSF did not affect other components of peripheral blood such as monocyte, lymphocyte, eosinophil, and hemoglobin value and platelet counts. Transient bone pain occurred in two patients receiving a dose of 800 micrograms/m2. The biochemical changes detected were increased total alkaline phosphatase activity in serum, which appeared in parallel with the increase of neutrophil numbers, and less elevation of total uric acid values. We conclude that an optimal dose of rhG-CSF is 100 micrograms/m2 (average maximum peripheral granulocyte count, 10799/microliters; nadir granulocyte count, 3772/microliters; period of neutropenia, 2.6 days), and rhG-CSF is useful for acceleration of neutrophil recovery and prevention of infection from chemotherapy.

Adolescent↗

PubMed1989

[A study to overcome drug resistance using high-dose chemotherapy with autologous bone marrow transplantation].

Drug resistant phenomenon to antitumor agents remains a major problem in cancer chemotherapy. In this study, we attempted to overcome drug resistance using high-dose chemotherapy with autologous bone marrow transplantation (ABMT). The main regimen consisted of Cyclophosphamide 60 mg/kg/day and thio-TEPA 6 mg/kg/day which were infused for 3 consecutive days. Three patients with malignant lymphoma, four with breast cancer, two with gastric cancer and one with ovarian cancer. All of whom were refractory to conventional chemotherapies were treated. The overall response rate was 70%. Severe bone marrow suppression, mucositis and diarrhea were observed in all patients, but these were not life-threatening and clinically manageable. Furthermore, the administration of granulocyte colony stimulating factor (G-CSF) has significantly (p less than 0.05) shortened the duration of leukopenia, and has been judged to be useful for reducing severe infections and for shortening the period stayed in clean room. Our results indicates that high-dose chemotherapy with ABMT is an effective method for overcoming drug resistance.

Adult↗

PubMed1989

[Evaluation on facial pattern of early childhood patients with T.M.J. dysfunction occurred after anterior crossbite correction].

The purpose of this study was to investigate the facial pattern of early childhood patient with temporomandibular joint (TMJ) dysfunction (clicking) occurred after anterior cross-bite correction. Chincap appliance was engaged in all cases, with or without minor intraoral mechano-therapy. Materials were consisted of lateral and postero-anterior cephalograms of 50 japanese patients (6-9 years old), all showing anterior cross-bite with normal function of TMJ at pre-treatment stage. They were consisted of two groups, one was the group of 22 patients with TMJ dysfunction occurred after cross-bite correction and the other was the control group of 28 patients with no TMJ problem. Morphological measurements were done and compared between two groups. The results were as follows: 1) There was no significant difference between the TMJ group and the control group from the lateral facial pattern. 2) The upper and middle facial skeleton were symmetry in both groups, but the maxillary alveolar legion (CMo, U 1) of TMJ group was significantly from the antero-posterior view. 3) On the lower face (mandible) of the TMJ group, it was pointed out that the position of Gonion was significantly asymmetry and L 1 point and Menton were disclosed to have severe lateral displacement. It was cleared that a high incidence of temporomandibular joint dysfunction was found in mandibular asymmetry cases. It was concluded that a careful case-management is required for mandibular asymmetry patients during chicap-orthodontic therapy.

Cephalometry↗