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Biomedical subjects

N Horikoshi

Publications and source records attributed to N Horikoshi.

At least 73 records · Page 4Linked to original sources
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

[A randomized trial comparing ACF (adriamycin, cyclophosphamide, ftorafur) and ACF/MVMF (mitomycin C, vincristine, methotrexate, ftorafur)--a non-cross-resistant alternating chemotherapy of recurrent and advanced breast cancer].

Of 47 consecutive patients with advanced breast cancer, we randomly assigned 24 to receive Arm A; ACF alone (Adriamycin, Cyclophosphamide, Ftorafur) and 23 to receive Arm B; 2 cycles of ACF alternating one cycle of MVMF (Mitomycin C, Vincristine, Methotrexate, Ftorafur--a combination of drugs not cross-resistant with ACF). The response rate was 66% in Arm A and 52% in Arm B. The median duration of response was significantly longer in Arm B (11 months in Arm A, 28.8 months in Arm B) due to prolongation of duration to administer adriamycin in Arm B. But the median survival time was 30.7 months in Arm A and 24.5 months in Arm B, and significantly longer in Arm A until 10 months. These results were due to the difference in response rate during induction therapy (58% in Arm A, 26% in Arm B) reflected in the dose intensity of Adriamycin (13 mg/m2/w in Arm A, 6.7 mg/m2/w in Arm B) and the higher CR rate in Arm A, because CR cases had a significantly longer survival than PR and NC cases in both arms. We suppose that achieving CR by an intensive regimen containing adriamycin and adopting a non-cross-resistant regimen can help prolong survival in advanced breast cancer.

Adult↗
PubMed1989

[A study of complete responders in cases of metastatic breast cancer treated with combination chemotherapy].

Twenty-eight patients with a metastatic breast cancer who have achieved a complete remission from a combination chemotherapy that included doxorubicin have been analyzed to ascertain the factors which affect the duration of the response and the survival time. The median duration of a complete remission was 26 months. Relapses occurred in 17 patients (61%), of which the median duration of the response was 18 months and 71% of the relapses occurred at the sites of the prior dominant disease. Most of the patients suffered a relapse while they were receiving maintenance chemotherapy. The number of metastasized organs were one or two in 89% of the patients. The dominant sites of the disease were mainly the visceral (61%) and soft tissue (29%), and the duration of survival was found to be longer in patients with a visceral metastasis. In the group of patients who experienced a recurrence 2 years or more after their operation showed a statistically longer remission and survival time than those who experienced a recurrence within 2 years. The duration of survival from the start of chemotherapy was 45.5 months for complete responders and 21 months for partial responders. This difference was statistically significant (p less than 0.001), though no difference was found between partial responders and "no-change" patients (18.5 months). The tendency towards a relapse at the site of the initial involvement and while receiving maintenance therapy suggests that the majority of patients with a metastatic breast cancer who achieved a complete remission with this combination chemotherapy still have a substantial subclinical residual tumor. Maintenance treatment should be investigated to ascertain the procedures and duration of therapy. Thus, these results have indicated that it is necessary to achieve a complete remission in order to obtain a long term survival.

Adenocarcinoma, Scirrhous↗
PubMed1989

[Phase I and pharmacokinetic study of KRN8602, a new morpholino anthracycline].

Phase I clinical trial of a new semi-synthetic morpholino anthracycline derivative, KRN8602, was performed. Sixteen patients with advanced malignant neoplasms refractory to standard chemotherapies received 27 courses at doses ranging from 1.5 mg/m2/day to 18 mg/m2/day by bolus injection for three consecutive days. The dose limiting toxicity was leukopenia, and a maximally tolerated dose was 18 mg/m2/day (day 1-3). The recommended dose and schedule for a phase II study is determined to be 12 mg/m2/day for three consecutive days at 3-4 weeks intervals. Among non-hematologic toxicities, nausea and vomiting were severe, but stomatitis and alopecia were rarely observed. Clinical signs of cardiotoxicity were not seen.

Aged↗
PubMed1989

[5-Fluorouracil, adriamycin, and mitomycin C (FAM) combination chemotherapy in adenocarcinoma of the parotid gland].

An adenocarcinoma of the parotid gland is a rare tumor and little is known about the efficacy of chemotherapy as a method of treatment. Four patients with a metastatic, or recurrent adenocarcinoma of the parotid gland were treated with a combination chemotherapy consisting of 5-fluorouracil, adriamycin, and mitomycin C (FAM): 5-fluorouracil 330-500 mg/m2, d1-3, q3w or tegafur 400-600 mg/m2 p.o. adriamycin 30-40 mg/m2 q3w, and mitomycin C 3-10 mg/m2, q1-2w. One patient with a lung metastasis showed a good partial response lasting for 19 months and another patient who was resistant to CDDP plus the adriamycin combination, having a lymph node, bone, and bone marrow metastases, had a partial response lasting for 31 months. Results have indicated that adriamycin is one of the effective therapeutic drugs and that FAM combination chemotherapy can provide some efficacy against a parotid cancer.

Adenocarcinoma↗
PubMed1989

[Cancer curable by chemotherapy: malignant lymphoma].

The trends in the rationale of chemotherapy for malignant lymphoma are to use combination regimen, non-cross resistant alternating regimen, and hybrid regimen. Long follow-up results of chemotherapy of lymphoma were summarized as follows: for Hodgkin's disease, MOPP regimen of 20 years from NCI in 188 patients (pts) with 84% CR rate and 54% (101 pts) relapse-free (RF) at 15 years, and MOPP-ABV hybrid regimen in 76 pts with 97% CR rate and 90% RFS rate at 7 years; for non-Hodgkin's lymphoma (NHL), results of three generations are reported: the first generations were the first generation (CHOP, BACOP, 40-50s% CR rate and 30s% long-term survivors), the second generation (Pro-MACE/MOPP, 70s% and 40-50s%) and the third generation (MACOP-B, 80s% and 60-70s%). MACOP-B regimen in 125 pts with large-cell lymphoma showed 84% CR rate and 69% RFS rate and 69% RFS rate at 6.5 years. In our studies with four regimens of VCP, AVCP, AVCP/EMLP and B-AVCR/EMVP, CR rate was 56% in 101 pts, and 26 pts are still in CR among 40 living pts. The CR rate and the RSF rate reported in Japan are generally still low for curability of NHL.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1989

[4'-(9-acridinylamino)-methanesulfon-m-aniside (AMSA) combination salvage therapy in refractory acute non-lymphocytic leukemia in adults].

Eight patients with acute non-lymphocytic leukemia in adults refractory to Daunomycin (DM)-based conventional regimens were treated with AMSA-based regimens. Complete remission (CR) was obtained in 4 (50%) and partial remission (PR) in 2 (25%). The median time to CR was 26.5 days and 3 cases achieved CR in the first cycle. The median duration of CR was 8.3 months. Hematologic toxicity was severe and the nadir (median) of leukocytes and platelets was 0.15 x 10(3)/microliters and 15.5 x 10(3)/microliters, respectively. Other adverse effects were mucositis, nausea.vomiting and hepatotoxicity which occurred over 50%, while cardiac toxicity was not observed. This study indicates that AMSA is clinically non-cross-resistant to DM and considered to be an active drug for salvage therapy.

Adolescent↗
PubMed1988

Modulation of hormonal induction of tyrosine aminotransferase and glucocorticoid receptors by aflatoxin B1 and sterigmatocystin in Reuber hepatoma cells.

Employing Reuber rat hepatoma cells, H4-II-E, the effects of aflatoxin B1 (AFB1) and sterigmatocystin (STC), which exhibit a similar cytotoxicity but a marked difference in hepatocarcinogenicity, on the hormonal induction of tyrosine aminotransferase (TAT), on glucocorticoid receptors, and on their nuclear acceptor sites were investigated. AFB1 strongly inhibited hydrocortisone-inducible TAT activity. The IC50 value was 0.2 micrograms/ml. AFB1 also showed weak inhibitory effects on insulin- and dibutyryl cyclic AMP-inducible TAT activities. In contrast, the IC50 of STC on hydrocortisone-inducible TAT activity was 3.5 micrograms/ml, about 10 times higher than that of AFB1. Dibutyryl cyclic AMP- and insulin-inductions were not depressed by STC. AFB1 inhibited the formation of cytosolic glucocorticoid receptor-hormone complexes (GRCs) but STC did not. Moreover, AFB1, activated in vitro by the microsomal cytochrome P-450 system, interfered more markedly in the formation of cytosolic GRCs than STC did. Sucrose density gradient analysis of GRCs and Scatchard analysis revealed that AFB1 and STC mainly impaired glucocorticoid receptors and GRC-acceptor sites, respectively. The present data suggest a marked difference between AFB1 and STC with regard to the inhibition of hormonal induction of liver specific enzymes.

Aflatoxin B1↗
PubMed1988

[Adriamycin, cyclophosphamide, ftorafur and tamoxifen (ACFT) in patients with advanced breast cancer].

One hundred and six patients with advanced breast cancer were treated with chemoendocrine therapy consisting of adriamycin (40 mg/m2) i.v. on day 1 and cyclophosphamide (130 mg/m2) i.v. daily for 5 days every 3 weeks, ftorafur (500 mg/m2) and tamoxifen (40 mg) orally daily. Of 82 evaluable patients, 16 showed complete response (20%), 32 partial response (39%), 32 no change (39%), and two progressive disease (2%). The overall response rate was 59%, and the median duration of response was 16.3 (3.5-67+) months with a median survival time from the start of chemoendocrine therapy of 25.5 (3.5-67+) months. The median survival time of responders (32.5 months) was significantly longer than that of non-responders (15.3 months). The major toxicities were hair loss, G1 symptoms, and hematological toxicity, but these were clinically well tolerated. No serious cardiac, renal or liver damage was seen. These results indicated that the addition of tamoxifen to the ACF regimen increased the number of complete responses and prolonged the survival time of responders.

Adult↗
PubMed1988

[Combination chemotherapy of 5-fluorouracil (5-FU), adriamycin (ADM), cis-diamminedichloroplatinum (II) (CDDP) and mitomycin C (MMC) (FAP.MMC) in advanced gastric cancer].

Twenty patients with advanced gastric cancer were treated with FAP.MMC (5-FU 350 mg/m2 i.v. on days 1-3, ADM 40 mg/m2 i.v. on day 1, CDDP 20 mg/m2 i.v. on days 1-3, MMC 6 mg/m2 i.v. on day 1), administering 5-FU, ADM and CDDP every 4 weeks and MMC every 8 weeks. Fourteen patients were evaluable for responses. Four (29%) partial responses and two minor responses were observed. The median duration of partial response was 3.8 months (range 2.5-7 months). The median overall survival time was 5 months (range 1.5-15 months). Leukopenia was relatively severe, with a median WBC nadir of 1,300/mm3. Nausea and vomiting were frequent but moderate. However, these toxicities were clinically manageable. FAP.MMC was thus considered effective for advanced gastric cancer.

Adult↗
PubMed1988

[Phase II study of combination chemotherapy with epirubicin, cyclophosphamide and ftorafur in metastatic breast cancer].

Twenty-nine patients with metastatic breast cancer were treated with a combination chemotherapy consisting of Epirubicin 50 mg/m2 IV on day 1, Cyclophosphamide 500 mg/m2 IV on day 1 and Ftorafur 800 mg/day PO every day (ECF therapy). The therapy was repeated every 3 weeks until progression or until a cumulative dose of 700 mg/m2 for epirubicin. Of 25 evaluable patients, there were one with complete response (CR), 11 with partial response (PR), 10 with no change and 3 with progressive disease (PD). The overall response rate (CR + PR) was 48%, and the median duration of response was 47 weeks. The median survival time was 78 weeks for responders and 60 weeks for non-responders, and the difference was statistically significant (p = 0.02). Leukopenia, alopecia, nausea and vomiting were commonly observed, but these side effects were better tolerated than those accompanying ACF therapy. As for cardiotoxicity, there were no acute abnormal E.C.G. changes and no congestive heart failure occurred. The median cumulative dose of Epirubicin was 510 mg/m2. These results indicate that ECF therapy is as effective as ACF therapy for metastatic breast cancer with considerably better tolerability.

Adult↗
PubMed1988

[Phase I 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. At 130 mg/m2 the median lowest WBC count was 0.7 x 10(3)/mm3 (range 0.3-1.8) and the median lowest platelet count was 57 x 10(3)/mm3 (range 4-176). Nonhematological side effects were mild gastrointestinal symptoms and hair loss. The recommended dose and schedule for a phase II setting is 100 mg/m2 every 3 weeks.

Adult↗
PubMed1987

[Combination chemotherapy with cis-platinum, vinblastine and adriamycin for non-small cell lung cancer].

A combination chemotherapy consisting of cis-platinum (CDDP), vinblastine (VLB) and adriamycin (ADM) was given to fourteen patients with non-small cell lung cancer. The treatment consisted of CDDP 60 mg/m2 i.v., divided over two days (on days 1 and 2) or five days (on days 1-5), and VLB 3.5 mg/m2 and ADM 40 mg/m2 i.v. on day 1 and repeated every four weeks. Of fourteen evaluable patients, there were two with partial responses (14%), eleven with no change and one with progressive disease. The durations of the partial responses were 3 and 4 months, respectively. The median time to disease progression in the patients with partial response plus no change was 6 months. The median survival time of all treated patients was 13.5 months. Leukopenia of less than 2,000/mm3 was seen in 36% and decreased hemoglobin of more than 1 g/dl in 50%. Mild transient renal dysfunction was observed in 7%, cumulative renal dysfunction in 29%, alopecia in 100%, nausea and vomiting in 93% and peripheral neuropathy in 43%. We conclude that a combination chemotherapy with CDDP, VLB and ADM has moderate activity against non-small cell lung cancer.

Aged↗
PubMed1987

[A phase I study of carboplatin].

A phase I study of carboplatin was conducted using a single dose schedule. Escalating doses of 200, 300, 400 and 500mg/m2 were administered without hydration up to a total of 21 cycles in 18 patients with various solid tumors. A dose-limiting factor was thrombocytopenia, and leukopenia was also dose-related. A major clinical toxicity was gastrointestinal toxicity, while nephrotoxicity was extremely mild. The optimal dose for phase II trials was judged to be 300mg/m2 q 4w in poor-risk patients and 400mg/m2 q 4w in good-risk patients, respectively. Pharmacokinetics were studied in 11 patients.

Adult↗
PubMed1987

[Phase II study of chlorambucil in patients with hematological malignancies].

Eight patients with various hematological malignancies were treated with chlorambucil, an analogue of nitrogen mustard. Five patients with CLL, 2 patients with malignant lymphoma, and one each with pseudolymphoma of the lung and primary macroglobulinemia were given 4-6 mg of chlorambucil per day for 1-2 weeks at 2-4 week intervals or a daily dose of 6 mg continuously. Two cases of CLL and one each of follicular lymphoma and pseudolymphoma achieved partial remission. Side effects included myelosuppression, especially leukopenia. Chlorambucil can be used orally without severe toxicity for longer periods and the major indication for this drug seems to be CLL and favorable type of malignant lymphoma.

Administration, Oral↗
PubMed1987

[Phase II study of prednimustine in follicular lymphoma and chronic lymphocytic leukemia].

A phase II study of Prednimustine (PMN) was conducted for follicular lymphoma (FL) and chronic lymphocytic leukemia (CLL). PMN at a dose of 40-60 mg/body, p.o. every day, was administered to 17 patients with FL and 4 with CLL. The dose and schedule of PMN was modified according to hematological toxicity. Among the 17 patients with FL, there were 6 (35.3%) CRs and 7 (41.2%) PRs, with a high response rate of 76.5%. Among the 4 patients with CLL, there were 2 PRs and one case which showed clinical improvement. PMN was effective for cases of FL and CLL refractory to alkylating agents, and therefore the result suggested a lack of clinical cross-resistance to these agents. As to the side effects observed in patients with FL, mild leukopenia (median of lowest count 3,150/mm3) occurred. One case experienced anorexia, while increased appetite was observed in 4 cases. We conclude that PMN is effective for FL and CLL, and that in addition, it has an advantage in that its mild side effects allow long-term administration through outpatient clinics, so that the quality of life for patients is not impaired.

Administration, Oral↗