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Biomedical subjects

H Furue

Publications and source records attributed to H Furue.

At least 91 records · Page 5Linked to original sources
PubMed1992

[Chemotherapy in the elderly].

Because of the increase in the incidence of malignancies with advancing age, we have need to make decision on the chemotherapy of elderly patients with cancer. However, until recently, studies about response to treatment and toxicities in the elderly patients have been quite limited. Many of clinical trials have excluded elderly patients with advanced cancer. In leukemia and Hodgkin's lymphoma, definite trends of decreased levels of response and survival in relationship to increased age have been reported. This reduced rates of response in elderly leukemia patients do not appear to be due to chemotherapy resistance but rather to high rates of death among elderly patients during remission induction therapy or to inadequate salvage therapy. On the other hand, older patients with solid cancers can be treated with chemotherapy as successfully as younger patients. General expectations of response, remission, and survival are similar for the older and younger patients. With the exception of small increase in the incidence of hematologic toxicity in the older group, both younger and older patients experience the same frequency of toxic reactions. Aging is a highly individualized process that cannot be defined by chronological landmarks. Therefore, it can be said that there is no reason to exclude from adequate chemotherapy, simply on the basis of age alone. But, observations on the proper role of chemotherapy in older patients are very limited, and further studies are needed in this area.

Aged↗
PubMed1992

[Antiemetics and its clinical evaluations].

Nausea and vomiting induced by anticancer agents are common problems associated with chemotherapy for cancer. Recent trials have examined a variety of antiemetics, representing several different classes of drugs. High dose metoclopramide provided the impetus for many of the current studies because of its effect against cisplatin induced vomiting. However, current regimens are not yet entirely effective in many patients receiving cisplatin or other highly emetogenic anticancer agents. A promising new class of antiemetics, 5-hydroxytryptamine receptor antagonists are undergoing clinical evaluations. Members of this class are easily and safely administered to patients receiving cisplatin or other emetogenic anticancer agents. These are highly active antiemetics, both prophylactic and interventional treatment. Lack of extrapyramidal reaction and other adverse effects associated with its use makes the drug a very attractive one. However, studies of antiemetics require consideration of methodologic issues that may not be of concern in trials of anticancer agents. The results of these studies can be affected by the patient population, the sample size, pharmacologic variables, the trial design, the method of analysis, etc. Recently, developments both in new-antiemetics and better ways of using the existing ones, lead us to cautious thought that nausea and vomiting due to cancer chemotherapy can be controlled substantially with benefit to the patients.

Antiemetics↗
PubMed1992

[A phase I study of DWA2114R].

Phase I study of DWA2114R, a new platinum analogue, was conducted in 39 patients with various tumor types by a group of 13 institutions. Of the 39 patients entered in this study, 35 were evaluable. The starting dose was 40 mg/m2 (1N) and the drug was administered i.v. for 20-30 min, escalating stepwisely up to 1,000 mg/m2 (25 N). The dose limiting factor (DLF) was leukocytopenia, especially neutrocytopenia, and the maximum tolerated dose (MTD) was more than 1,000 mg/m2. Major clinical toxicity was gastrointestinal. Hepatotoxicity and nephrotoxicity were mild. Following administration of the drug, plasma concentrations of total and filterable platinum (Pt) showed a triphasic and biphasic decays. Excretion into urine within 24 hours was in the range of 54.2% to 92.2% of the administered platinum. The recommended dose of phase II study was 800-1,000 mg/m2, repeating every 3-4 weeks.

Adult↗
PubMed1991

Clinical outcome of postoperative adjuvant immunochemotherapy with sizofiran for patients with resectable gastric cancer: a randomised controlled study.

Adjuvant immunochemotherapy using the antitumour polysaccharide sizofiran (SPG), an extract from the culture broth of Schizophyllum commune Fries, was prescribed randomly for 386 Japanese patients with resectable gastric cancer. Although the overall survival probability for 5 years did not differ between the SPG and control groups, in 264 patients with curatively resected cancer, the probability to 5 year survival and to recurrence in the sizofiran-administered patients was better than in the controls. In the multivariate analysis, four of six prognostic factors correlated with the prognosis of the 264 patients who underwent curative surgery, that is, nodal involvement (chi 2 = 21.426, P = less than 0.0001), age distribution (chi 2 = 9.262, P = 0.010), sizofiran administration (chi 2 = 6.507, P = 0.011), and primary tumour size (chi 2 = 9.345, P = 0.025). Thus, patients with a curatively resected gastric cancer had a better prognosis when sizofiran was prescribed in combination with antitumour drugs.

Adjuvants, Immunologic↗
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

[Systemic chemotherapy of colorectal cancer--recent approaches].

Progress in the treatment of cancer with drugs has altered the clinical approach to patients with cancer. However, chemotherapy used as sole treatment for colorectal cancer has not been generally successful in providing palliation or improving patient life span. This article describes the recent new efforts to improve the effectiveness of chemotherapy: including combination chemotherapy, biochemical modulation, combination of 5-fluorouracil and interferon, quality of life assessment in chemotherapy, and clinical issues of adjuvant chemotherapy. However, available data from these studies dose not establish a true therapeutic advance in the treatment of colorectal cancer, and do provide a strong scientific rationale for well-controlled randomized clinical trials. Furthermore, there is a strong imperative for the development of new therapeutic strategies in this disease.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1991

[Evaluation of cardiotoxicity in new anthracycline analog ME 2303. ME 2303 Study Group].

ME 2303 is a new anthracycline analog which differs from adriamycin in the sugar moiety. ME 2303 displays a higher antitumor activity against L 1210 and P 388 Leukemia than adriamycin. To evaluate the cardiotoxicity of ME 2303, ECG tracings (21 patients) and Holter ECGs (9 patients) were recorded before and after the administration of ME 2303 for various malignancies (mean dose 123.8 mg/m2), and some of the electrocardiographic parameters were analyzed. Control ECGs were normal in 17 patients, in 4 patients minor ECG findings like sinus tachycardia (2 patients), low voltage (1 patient) and flattening of the T wave (1 patient) were observed. After treatment, no relevant ECG changes were observed except one case who showed a flat T in pretreatment ECG. In this patient developed ST-T changes were seen after treatment. The basic rhythm was sinus rhythm in all of the cases, and the heart rate showed no significant changes. ME 2303 had no effects on the specialized conduction system. With regard to arrhythmia, no increase in number and severity was observed. In Holter ECG no development of ST-T changes was seen after treatment.

Adult↗
PubMed1990

[A phase I study of weekly administration of CPT-11 in lung cancer].

A clinical study of weekly administration of CPT-11, a semi-synthetic derivative of Camptothecin, was performed in patients with advanced lung cancer to determine the optimal dose for a weekly single dose schedule. Sixteen out of 19 patients enrolled were evaluable. The starting dose was 50 mg/m2 and gradually escalated to 100, 125 and 150 mg/m2. CPT-11 was given by intravenous infusion for 90 minutes every week. The maximum tolerated dose for this schedule was estimated to be 125 mg/m2. The dose-limiting toxicity was leukopenia with median nadir of 2,900/mm3, median day to nadir of 21, and median day to recovery of 7. Other major toxicity was gastrointestinal upset, but was mild and tolerable. Objective tumor responses were observed in four patients, three with non-small cell carcinoma and one with double cancer (small and non-small cell carcinoma). The responding patients were treated at a dosage of 100 mg/m2 or more. The recommended dose for a phase II study is considered to be 100 mg/m2 iv infusion for a weekly single-dose schedule.

Aged↗
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↗
PubMed1990

[Phase I clinical study of CPT-11. Research group of CPT-11].

CPT-11 is a new derivative of Camptothecin. Phase I clinical study of single administration with CPT-11 was carried out by a cooperative study group. Starting from 50 mg/m2 (n), dose was escalated to 350 mg/m2 (7n). Dose limiting factor was found to be a decrease in WBC counts (especially in neutrophils), and MTD was presumed to be 250 mg/m2 or more. Nadir of WBC counts was observed after about a week, and it took 2-3 weeks for recovery. The decrease in platelet number and hemoglobin content was mild. Other side effects included G-I toxicities, alopecia, etc. However, no toxic effects on the heart, kidney, lung were observed. SN-38, main metabolite of CPT-11, was observed in blood, and excreted rapidly. Anticancer effects were suggested with dose of 165 mg/m2 or more against colon cancer, gastric sarcoma, melanoma and lung cancer. It is suggested that the optimal dose schedule for an early Phase II study is 200 mg/m2 every 3-4 weeks. However, not only leukopenia but also marked G-I toxicities being noted in some cases, care should be taken for those side effects.

Adult↗
PubMed1989

[Problems in evaluating the effects of cancer chemotherapy].

A clinical response of a solid tumor can obviously be defined as some measurable reduction in the patients total tumor burden lasting for at least one month. However, this is a variable definition. Many pitfalls exist in interpreting improvement in a measurable criterion of response as evidence of an anticancer effect. Measurement error on palpation has been widely mentioned. Furthermore, on the x-ray examination, it is difficult to be sure that we are measuring even accurately across the same planes from one examination to the next. Patients with only non-measurable (but evaluable) lesions should be excluded from those clinical trials that are designed to assess response. Because of measurement error, minor response and stable disease categories should be abandoned unless they are of long duration. A period of regression lasting for only one month usually conveys little or no benefit in terms of quality or quantity of life to patients. To search for antitumor activity in a modality by using survival as an endpoint is a far too complex and time-consuming effort. In some rare tumors biochemical measurements performed on peripheral blood give an indication of the total tumor burden. However, in the most common tumors, no such reliable markers exist. One more major deficiency in assessing response to treatment is the lack of methods for reliably assessing the quality of life of the treated patients. Furthermore, large differences in rates of response are probably due to variable and inappropriate exclusion of patients from analysis of results. Differences in policies for excluding patients from analysis are a source of variation in reporting the results. We believe that some measure of change in tumor size will continue to be viewed as an acceptable endpoint until better methods of assessing response become available. On the other hand, at present, since we cannot eliminate the measurement error, it would seem advisable to make an effort to understand it, to learn how great an effect it can have on the validity of reporting results, and consider how to defend against it. Finally, more stringent criteria that relate to the true clinical benefit be required as measures of response to treatment.

Antineoplastic Agents↗
PubMed1988

[Interferon-alpha].

Among interferon (IFN)-alpha, beta, gamma, there are no differences in its clinical effects and toxicities. As to IFN-alpha, there are leukocyte IFN, lymphoblastoid IFN, recombinant IFN-alpha 2a, 2b, and 2c. Now we have largely completed the process of surveying for anticancer effects over the broad range of malignancies. However, the adequate method of administration, route, dose, and interval are not yet fully established. Dose response remains unanswered question with some contradictory results in in vitro and clinical reports. The actual mechanism responsible for its anticancer activity is still not known. The question of what variables to monitor in assessing adequate dosages of IFN remains unsolved. Several trials have examined the possibility of combining IFN with other treatment modalities including anticancer agents, BRMs, radiation, etc. It should be acknowledged that we remain at a very early stage in our understanding of IFN. In future, IFN may play an even larger role when used in an adjuvant setting or as part of multimodality cancer treatment.

Drug Evaluation↗
PubMed1987

Phase I study of recombinant human tumor necrosis factor.

A phase I clinical and pharmacokinetic study of recombinant human tumor necrosis factor (rH-TNF) was conducted in a single dose schedule in 33 patients with advanced cancer. rH-TNF was given by i.v. infusion over 30 min with a starting dose of 1 x 10(5) units/m2. The dose was escalated up to 16 x 10(5) units/m2 according to the modified Fibonacci scheme. Toxic effects were similar but not identical to those reported with interferons and interleukin-2, and included fever, rigors, nausea and vomiting and anorexia in a non-dose-dependent manner, and hypotension, leukocytosis, thrombocytopenia and transient elevation of transaminases (SGOT and SGPT) in an approximately dose-dependent manner. DIC syndrome was observed in one patient who had received 16 x 10(5) units/m2. The dose-limiting toxicities were hypotension, thrombocytopenia and hepatotoxicity, and the maximum tolerated dose in a single i.v. infusion of rH-TNF appeared to be 12 x 10(5) units/m2 when thrombocytopenia and elevation of SGOT and SGPT were taken as the dose-limiting toxicities. However, if hypotension was included, the maximum safely tolerated dose appeared to be 5 x 10(5) units/m2.

Adult↗
PubMed1987

[Interferon production in vitro].

Interferon production in vitro was induced by poly I: C and PHA in leukocytes obtained from patients with cancer, benign diseases and control subjects. The interferon response per lymphocyte was relatively constant in all groups. However, interferon production was slightly inhibited in patients receiving cancer chemotherapy. The peak response of interferon occurred at 48 hours after the initiation of the combined culture in each specimen. From our observations, it was suggested that interferon production in vitro seems to be useful marker for evaluation of effect of chemotherapy and or immunotherapy, and, furthermore, in the treatment of cancer patients with interferon inducers, there seems to be optimum BRM dose and optimum timing of administration.

Cell Wall Skeleton↗
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↗