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Biomedical subjects

I Nakao

Publications and source records attributed to I Nakao.

At least 37 records · Page 2Linked to original sources
PubMed1991

[Phase I study of CI-898. CI-898 Study Group].

We conducted a phase I study of CI-898 (trimetrexate), a new diaminoquinazoline antifolate in 22 patients with solid cancer in a multicenter collaborative study. The dosage schedule was single-dose intravenous administration (single treatment), followed by one or two courses of 5-day intravenous administration (5-day treatment) at 3-week intervals. Starting at 2 mg/m2 (1 n), the dose was increased up to 15 mg/m2 (7.5 n) for single treatment and 12 mg/m2 (6 n) for 5-day treatment. Evaluable cases numbered 18 for single treatment and 17 for 5-day treatment. In single treatment, the highest dose of 15 mg/m2 caused no serious side effect and did not reach the maximum tolerated dose (MTD). In 5-day treatment, leukocytopenia and thrombocytopenia were found dose dependently, the dose-limiting factor was bone marrow depression, and MTD was 10 mg/m2/day. The leukocyte and platelet counts reached the nadir in 1-3 weeks after initiation of 5-day treatment. The recovery from the nadir required about one week. Subjective side effects included mucitis (mouth, anus), malaise and gastro-intestinal symptoms (nausea, anorexia, diarrhea). None of alopecia, cardiotoxicity and nephrotoxicity were found. In the present phase I study, a tendency of tumor reduction was found in one case each of breast cancer (adenoma) and lung cancer (squamous cell carcinoma). The plasma concentration of the unchanged compound after single treatment showed a biphasic elimination pattern (t1/2 alpha 0.8-1.4 hr, t1/2 beta 9.4-13.0hr). The urinary excretion of the unchanged compound was 14.7-23.5% of the administered dose. In 5-day treatment, no accumulation was found. From the results of the present study, the recommended dosage of CI-898 in the early phase II study was considered to be 8 mg/m2/day intravenously for 5 days (every 3-4 weeks).

Adult↗
PubMed1991

[An early phase II study of CPT-11 in primary lung cancer].

An early phase II study of CPT-11 was carried out in patients with primary lung cancer in 15 institutions throughout Japan. The efficacy and safety of CPT-11 were studied at 200 mg/m2 based on the results of the previous phase I study. Thirty-eight of 52 enrolled patients were eligible. CPT-11 proved to be effective for primary lung cancer. The response rates were 20.0% (7/35) for non-small cell lung carcinoma and 33.3% (1/3 for small cell lung carcinoma. Hematological toxicities included leukopenia (less than or equal to 3,000) in 44.7% of the patients. Other major toxicities were nausea/vomiting (greater than or equal to grade 2) in 50.0% and diarrhea (greater than or equal to grade 2) in 47.4%.

Adenocarcinoma↗
PubMed1991

[Phase II study of (2" R)-4'-O-tetrahydropyranyladriamycin (THP) in patients with advanced or recurrent gastric cancer. Clinical study group of THP for gastric cancer in Japan].

A multi-institutional collaborative phase II study of (2"R)-4-O-tetrahydropyranyladriamycin (THP) was performed by intravenous administration to patients with advanced or recurrent gastric cancer. The administration schedules were (1) 40-60 mg/body every 3 or 4 weeks and (2) 20-40 mg/body once a week. Of 58 registered patients, 49 cases were eligible and 37 cases were evaluable for response. The therapeutic results were 1 CR, 4 PR, 14 NC and 18 PD. The response rate of the evaluable cases was 13.5%. The side effects were mainly bone marrow suppression and digestive symptoms. In particular, the frequency of leukopenia was a high 75.5%, while there was a decrease in hemoglobin in 38.8% and anorexia in 30.6%. The frequency and severity of alopecia, which is a known problem with anthracyclines, were slight, and no abnormal electrocardiograms were observed.

Adenocarcinoma↗
PubMed1990

[Combination chemotherapy of non-small cell lung cancer (NSCLC) with cisplatin (CDDP), carboquone (CQ) and prednisolone (PDN)(PPQ therapy)].

Twenty-five courses (twenty-two pts) with NSCLC have been entered in the trial evaluating the combination of CDDP 20 mg/m2 i.v. day 1, 2, 3, 4, 5, CQ 7 mg/m2 i.v. day 1, and PS 30 mg/body per os day 1, 2, 3, 4, 5, repeated every 4 weeks. Except for 1 case of early death, judgement of efficacy was possible in 24 courses, including one case of squamous cell carcinoma and 23 cases of adenocarcinoma. CR was obtained in no cases and PR in 7 cases, all of which were adenocarcinoma, with an efficacy rate of 29%. Response for primary site was obtained in 4 of 22 cases (18%). Median survival time of the 22 cases was 11.5 months. Main side effects of PPQ Therapy were symptoms in digestive organs such as nausea and loss of appetite, and bone marrow inhibition. Renal dysfunction was controllable by measures to cope with diuresis.

Adenocarcinoma↗
PubMed1990

[Lymphocyte subset change during cancer chemotherapy on patients with gastrointestinal, lung and hematopoietic malignancies].

Lymphocyte subsets measured by Ortho-mune on OKT 3, OKT 4A, OKT 8, OKT 10, OKT 11, OKM1, OKB 7, OKB 2 and OKDR were observed before and after chemotherapy on patients with gastrointestinal, lung and hematopoietic malignancies. Almost all patients showed decreased T-cell function expressed by OKT 11 or OKT 3 and suppressor, helper T-cell function expressed by OKT 8 and OKT 4A. In some patients improvement of T-cell function were observed with clinical response and in such cases life span seemed to be longer as expected, and it is supposed that during cancer chemotherapy improvement of T-cell function expressed by OKT series may be important prognostic factors.

Adult↗
PubMed1990

[Prostaglandin-E2 (PGE2) and interleukin-1 (IL-1) production from plastic-adherent peripheral blood mononuclear cells, and serum and urinary glucocorticoid levels in cancer patients treated with systemic chemotherapy--with special reference to circadian rhythm of serum cortisol levels in cancer].

Prostaglandin-E2 (PGE2) and interleukin-1 (IL-1) production from plastic-adherent peripheral blood mononuclear cells stimulated in vitro by bacterial lipopolysaccharide, serum and urinary glucocorticoid levels and the circadian rhythm of serum cortisol levels were studied for better understanding of the immunological and physiological changes produced by systemic chemotherapy in cancer patients. In one responded patient out of four, PGE2 production decreased and IL-1 production increased, whereas the serum cortisol level decreased and the urinary 17-KS excretion level increased. The circadian rhythm of the serum cortisol level was evaluated three times a day, at 7 A.M., 2 P.M. and 10 P.M. Healthy volunteers showed a peak level at 7 A.M. which decreased gradually towards evening and reached to the lowest level at 10 P.M. In contrast, cancer patients showed three additional patterns. These patterns were classified as follows, Type N showed a maximal level at 7 A.M. and minimal level at 10 P.M. as same as in healthy subjects. Type V showed a minimal level at 2 P.M. while type A showed a maximal level at this time. In type F the serum cortisol level was no greater than 1.0 micrograms/dl at any of the three time points. We examined circadian rhythm in four cancer patients treated with systemic chemotherapy. In one PR case, the circadian rhythm shifted from type V to N after the first course of therapy, then changed to type F after subsequent and another courses of the therapy. In another PR case, type N persisted during and after therapy. One MR case shifted from type A to type N. In contrast, one PD case shifted from type N to A. There results suggest that normalization of the circadian rhythm of serum cortisol was associated with the improvement in host body condition achieved by chemotherapy and that systemic chemotherapy modified the immunological and physiological state of cancer patients, as defined above. This may eventually be beneficial for patients.

Adult↗
PubMed1990

[Home administration of anti-cancer drug with Baxter infusor].

Baxter infusor was evaluated for the degree of its safeness, and effectiveness, to use in a chemotherapy. The study covered a total of 36 cases, each receiving an average 11 days of care under this therapy. In seventeen of those cases, the patient had received outpatient care, or had spent day and night at their homes. In nine of the total 36 cases, the infusor had been set for use by the patients or by their family. Results were evaluated with a focus on three factors: the patients' quality of life, the infusor's ease of use and its comparability to conventional systems. As to quality of life, those patients generally appreciated the infusor as an improvement to conventional systems with 10 of them citing "an ability to live with their family", 16 citing "freedom to move around", and 35 citing "satisfying functional performance", as reasons for their favorable acceptance. 97% of the patients had found the infusor easy to use, and all had found it simpler and easier to use than the conventional system. Their overall rating for the infusor was "good" to "excellent" in 97% of the cases. And 33 out of the 36 patients thought the infusor safe and effective if used at the homes.

Adult↗
PubMed1990

[Phase I study of MST-16].

Phase I study with a new oral anticancer agents. MST-16 (Sobuzoxane), was conducted by 3 administration schedules: single, 5 consecutive days and 10-15 consecutive days. No toxicity was observed in the single administration at doses escalated up to 1,500 mg/m2. Dose-dependent leukopenia was observed from 560 mg/m2/day in consecutive 5 day administration, and median days to the nadir and recovery were about 2 and 1 week, respectively. GI-disorders were also observed sporadically from 800 mg/m2/day. One patient with Hodgkin's disease receiving 1,000 mg/m2/day achieved complete response. Consecutive administration for 10-15 days was carried out at a dose of 800 mg/m2/day. Six out of 7 evaluable patients demonstrated leukopenia, and all 2 patients treated for 15 days experienced leukopenia with a nadir corresponding to grade 3. Median days to nadir and recovery were both about 2 weeks. Doses recommended for phase II study were considered to be 1,600 mg/body/day for 5 days and 1,200 mg/body/day for 10-14 days.

Adolescent↗
PubMed1989

Effects of recombinant granulocyte colony-stimulating factor (rG-CSF) and recombinant granulocyte-macrophage colony-stimulating factor (rGM-CSF) on acute radiation hematopoietic injury in mice.

We have attempted to evaluate in vivo effects of granulocyte colony-stimulating factor (G-CSF) and granulocyte-macrophage colony-stimulating factor (GM-CSF) on acute radiation hematopoietic injury in mice. BDF1 mice, irradiated with 7.5-Gy x-rays, were injected i.p. twice daily for 10 days with 10(5) U recombinant human G-CSF, 3.75 x 10(5) U recombinant murine GM-CSF, or a combination of both. G-CSF significantly enhanced the recovery of not only peripheral leukocytes but also platelets and hematocrit on days 14 and 21 after irradiation. GM-CSF significantly enhanced the recovery of platelets on day 14 and peripheral leukocytes on day 21. G-CSF markedly enhanced the recovery of spleen colony-forming units (CFU-S), colony-forming units in culture (CFU-C), erythroid burst-forming units (BFU-E), and megakaryocyte colony-forming units (CFU-Meg) both in bone marrow and in the spleen. GM-CSF significantly enhanced the recovery of CFU-Meg in bone marrow on day 14. We found synergistic effects between G-CSF and GM-CSF on CFU-S, CFU-C, and CFU-Meg in the spleen on day 14, although we found antagonistic effects between G-CSF and GM-CSF on CFU-S and CFU-C in bone marrow on day 7, and on platelet counts on day 7. These results indicate that the administration of recombinant G-CSF and GM-CSF may be useful in accelerating hematopoietic recovery in patients with acute radiation hematopoietic injuries.

Acute Disease↗
PubMed1989

[Adverse reactions to carcinostatics and countermeasures].

As adverse reactions to the combination treatment by the digestive system, we observed the occurrence of nausea and vomiting in 15% of the cases who received FTP treatment consisting of 5-FU, toyomicin and prednisone, 25% of the cases who received MFU treatment consisting of MMC, 5-FU and ACNU, and in 64% of the cases who received PPQ treatment consisting of CDDP, Carboquone (CQ) and prednisone. The antiemetics usually used are metoclopramide and droperidol, and we preadminister valproate preparation when persistent and delayed emesis is predicted. Several randomized trials have been made, and good efficacies with drugs such as metoclopramide, domperidone and steroid have been reported. Efficacy was good with acute emesis, but nonexistent with delayed emesis. As to the liver injury, in our combination treatment, only one case showed elevation of GPT by more than 500 units in the cases treated with MFU, while, increase in liver enzymes in the blood was observed in 10-20% of the cases. Similarly, there were not so many cases of liver injury during PPQ treatment. Thus, liver injury due to carcinostatic would be less frequent. Moreover, autopsy revealed hepatocellular-type of liver injury, cholestatic type liver injury and fatty metamorphosis at reasonable incidence. There were no typical cases of veno-occlusive disease which are noticed recently. The most important point for prevention and countermeasures against liver injury is to be careful not to use the previously mentioned drugs exhibiting toxicity in the liver if hepatic disease exists.

Antiemetics↗
PubMed1989

[Some problems of the criteria for response evaluation of cancer chemotherapy of the digestive organs].

The criteria for response evaluation of cancer chemotherapy of digestive organs were discussed on the clinical application of stomach and esophagus cancer which the criteria are almost established. The responses of primary site are evaluated on the changes of tumor size by imaging diagnosis, and the uniformity and objectivity of response representation due to the sort of lesion cause the problems, so for studies are carrying out in many cases. Furthermore, response rate, survival time and quality of life were discussed in relation to clinical studies how to manage it at present and the problems in future referred. The criteria for response evaluation is a rule and interpreted different senses due to the objects of clinical studies. According to accumulate the clinical studies with exact significances and objects, various problems will be solved.

Antineoplastic Agents↗
PubMed1988

Induction of anomalous killing activity from antigen-specific CTL clones by adding high doses of human recombinant interleukin 2.

Four out of six long-term murine cytotoxic T lymphocyte (CTL) clones specific for trinitrophenyl (TNP)-modified spleen cells could develop an anomalous cytotoxicity against syngeneic and allogeneic tumor cells upon stimulation with TNP-modified spleen cells and high doses of human recombinant interleukin 2 (rIL-2). On FACS analysis, hyperactivated CTLs were positive for Thy-1, Ly 2 and LFA-1, but negative for L3T4 and asialo GM1. The staining profile of the cells with each antibody indicated that the CTL clones consisted of just one cell type. Monoclonal anti-Ly 2.2 and anti-LAA (lymphokine-activated cell-associated antigen) antibodies inhibited cytolysis of CTL and hyperactivated CTL clones against TNP-modified spleen cells, but failed to inhibit the anomalous killing of the hyperactivated CTL. The cold target competition test suggested the degeneracy of antigen specificity. The present study demonstrated that the CTL clone acquired a new specificity for tumor target cells upon stimulation with a high dose of rIL-2.

Animals↗
PubMed1987

[FO-152].

5'-O-(L-valyl)-5-fluorouridine hydrochloride (FO-152) is a derivative of 5-fluorouridine. In preclinical studies, FO-152 has demonstrated more favorable antitumor effect with greater therapeutic index compared with the parent compound, 5-fluorouridine. A phase I study was performed in 38 cases with advanced cancer. Myelosuppression was dose limiting, with leukopenia more pronounced than thrombocytopenia. Other side effects included mild hot feeling of the body during infusion and slight G.I. toxicities. Clinical responses were seen in patients with adenocarcinoma of the stomach, lung, etc. FO-152 has major advantages over 5-fluorouridine in terms of reduced toxicity. The recommended phase II dose for patients with solid tumors is 250 mg/m2 X 1, or 35 mg/m2 X 5 consecutive days with a 4-week rest, provided there is reversal of drug related myelosuppression.

Absorption↗
PubMed1987

In vivo radiosensitivity and recovery pattern of the hematopoietic precursor cells and stem cells in mouse bone marrow.

Survival curves were determined for colony-forming hematopoietic stem cells (CFU-Mix and CFU-S10) as well as precursor cells (CFU-E, CFU-C, CFU-F, and BFU-E) in bone marrow of the mouse at various times up to 4 weeks after whole-body irradiation (1.5 or 3.0 Gy) in order to elucidate in vivo radiosensitivity and recovery patterns. These measurements represented the first attempts to examine CFU-Mix simultaneously with the other cell populations. CFU-E (D0 = 53 rad) and BFU-E (D0 = 68 rad) were the most radiosensitive. CFU-S10 (D0 = 81 rad) had intermediate radiosensitivity. CFU-Mix (D0 = 144 rad) and CFU-C (D0 = 157 rad) were relatively radioresistant. CFU-F (D0 = 257 rad) was the most radioresistant. The precursor and stem cells could be classified into three groups based on the recovery pattern. The first group, consisting of CFU-Mix, BFU-E, and CFU-S10, showed very slow recovery and did not reach normal levels even after day 28. CFU-E, the second group, showed the most severe depletion immediately after irradiation, and recovered most quickly with an overshoot at day 5. CFU-C and CFU-F cells, forming the third group, decreased more gradually and slightly, and recovered to the normal level after a transient rise by day 10-14.

Animals↗
PubMed1987

[Prostaglandin E2 and interleukin-1-producing activity of plastic-adherent cells from cancer patients as a result of modification by BRM therapy].

It is crucial to define the immunological characteristics of peripheral blood mononuclear cells in order to clarify the physiological state of cancer patients. In this study, we examined prostaglandin E2 (PGE2) and interleukin-1 (IL-1) production by plastic-adherent cells stimulated by lipopolysaccharide (LPS). The secretion of PGE2 and IL-1 into media depended on the dose of LPS. Although the addition of silica resulted in suppression of LPS-induced PGE2 production, it caused augmentation of IL-1 production. The effect of BRM therapy on IL-1 production was evaluated in five cancer patients. The results demonstrated that BRM therapy increased the levels of IL-1 at the late assessment point for 3 patients and their quality of life was improved. These findings suggest that production of IL-1 may be used as a monitor for the effectiveness of biotherapy. The association of PGE2 production with host antitumor response was evaluated in IFN-gamma therapy. The results showed that the PGE2 production ratio increased early in the therapy period and declined gradually, whereas the expression of HLA-DR antigen on monocytes and the level of IL-1 increased during the treatment. The exact mechanism by which BRM activates monocytes is unknown. It is possible that a distinct subpopulation of monocytes is responsible for this effect.

Biological Products↗
PubMed1986

[Phase I study of bestrabucil (KM 2210)].

A phase I study was performed on a newly developed antitumor agent, Bestrabucil (KM 2210). The study was started at an initial dose of 1 n 25 mg/body, and gradually increased up to 32n 800 mg/body. With single (35 patients) and five-consecutive-day (36 patients) administration, the dose-limiting factor was found to be tarry stool, remarkable decrease in hemoglobin content, and strong nipple and breast pain. The maximum tolerated dose (MTD) was concluded to be around 700 to 800 mg/body. With long-term administration (the longest term, 20 weeks, 36 patients), the dose-limiting factor was concluded to be a decrease in the peripheral leukocyte count when the total amount administered reached about 10 g. Side effects on the alimentary system due to this agent, such as vomiting, nausea and anorexia, were observed. In addition, mastalgia and genital bleeding due to released estrogen were also seen, especially in the case of long-term administration.

Adult↗
PubMed1986

[Hepatic failure and renal failure in antineoplastic chemotherapy, and its treatment].

Various degrees of hepatic failure and renal abnormality may occur as complications of anti-neoplastic chemotherapy. The etiologies of alterations in liver function and the clinical pictures of chemotherapeutic agents as potential hepatotoxins, and of drugs with hepatic metabolism, and their combination uses, are discussed. As strategies are available for prevention and amelioration of these problems, management by periodic reevaluation of liver function is most important. In renal failure, myeloma kidney as tumor-associated nephropathy, hyperuricemic nephropathy and treatment-related nephrotoxicity are discussed with regard to their etiologies and clinical pictures. Aggressive management with intravenous hydration can ameliorate these complications of therapy, and careful monitoring of renal function and serum electrolytes are essential during administration of these agents.

Antineoplastic Agents↗