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Biomedical subjects

M Matthias

Publications and source records attributed to M Matthias.

At least 19 recordsLinked to original sources
PubMed1996

Clinical experiences with magnetic drug targeting: a phase I study with 4'-epidoxorubicin in 14 patients with advanced solid tumors.

Anticancer drugs reversibly bound to magnetic fluids (ferrofluids) could be concentrated in locally advanced tumors by magnetic fields that are arranged at the tumor surface outside of the organism. If certain requirements are met, systemic toxicity might be minimized, and local tumor efficacy might be increased. We have conducted a Phase I clinical trial using this approach in patients with advanced and unsuccessfully pretreated cancers or sarcomas. Nine such patients received two treatment courses, 3 patients received one course, and 2 patients received three courses of magnetic drug targeting consisting of the infusion of epirubicin in increasing doses (from 5 to 100 mg/m2) that had been chemically bound to a magnetic fluid and the application of magnetic fields to the tumors for 60-120 min. In 2 of 14 patients, the same dose of epirubicin not bound to a magnetic fluid was administered systemically 3 weeks after drug targeting for intraindividual comparisons. Magnetic drug targeting with epirubicin was well tolerated. In one case, a planned second treatment was withdrawn, because of an episode of chills 130 min after infusion of the magnetic drug. Two patients received a third treatment because of good responses after the first two therapies. Based on magnetic resonance tomographic techniques, pharmacokinetics, and the histological detection of magnetites, it was shown that the ferrofluid could be successfully directed to the tumors in about one-half of the patients. Organ toxicity did not increase with the treatment, but epirubicin-associated toxicity appeared at doses greater than 50 mg/m2. Although treatment with magnetic drug targeting seems safe, improvements are necessary to make it more effective and independent of patient- or disease-related problems. A study design to compare conventional treatments with the new treatment form within one patient seems crucial to eliminate interindividual differences.

Adolescent↗
PubMed1992

A phase II trial of interferon alpha-2b with folinic acid and 5-fluorouracil administered by 4-hour infusion in metastatic colorectal carcinoma.

Preclinical data suggest that folinic acid as well as interferon alpha-2b may enhance the antitumor activity of 5-fluorouracil (5-FU). In a phase I trial, we recently showed that interferon alpha-2b (IFN), folinic acid and 5-FU can be safely administered with a 4-hour infusion of 5-FU. We therefore initiated a phase II trial evaluating the efficacy and safety of these three drugs. Forty-five evaluable patients with advanced metastatic colorectal cancer, documented progressive disease, and previously unexposed to chemotherapy were treated with sequential IFN 5 MU/d subcutaneously and folinic acid 200 mg/m2/d as bolus on days 1 to 7 followed by 5-FU in a 4-hour infusion at a dose of 500 mg/m2/d, resulting in a total dose of 3,500 mg/m2/course. This schedule was repeated on day 21. A total of 204 courses of therapy were completed. One of 45 patients (2%) achieved a complete response, and 13 of 45 patients (29%) achieved a partial response. An additional 16 patients (36%) had stable disease. The median time to disease progression was seven months (2 to 24 months). Despite the relatively high-dose intensity of 5-FU, toxicity was very mild. Grade 3 or 4 myelosuppression, stomatitis, and nausea/vomiting occurred in only three of 45 patients (7%). Four of 45 patients (9%) suffered from severe (grade 3/4) diarrhea. Neurotoxicity and infections of grade 2 to 4 did not occur. From these data we conclude that modulation of 5-FU with both folinic acid and IFN induces an overall response rate of 31% in disseminated colorectal cancer. Using a 4-hour application schedule of 5-FU, the therapeutic index can be improved even for high-dose intensity and requires further evaluation in combination with other modulators.

Adult↗
PubMed1992

A phase I trial of interferon alpha-2b with folinic acid and 5-fluorouracil administered by 4-hour infusion in metastatic colorectal carcinoma.

Preclinical data suggest that both folinic acid and interferon may enhance the efficacy of 5-fluorouracil (5-FU) in colorectal carcinoma. We therefore initiated a phase I trial evaluating the doses, safety, and pharmacokinetics of the combination of recombinant interferon (IFN) alpha-2b with folinic acid (FA) and 5-FU. Seventeen patients with colorectal cancer who failed local chemotherapy received 5-FU as a 4-hour infusion, preceded by a bolus of FA and IFN. The 5-FU dose was escalated over the range of 400 to 650 mg/m2/d for a period of 7 days. Folinic acid was administered as a bolus in a fixed dose of 200 mg/m2/d and IFN as 5 million U/d subcutaneously on days 1 to 7. A total of 89 courses of therapy were completed for the 17 patients, of which there were 10 paired courses with a combination of 5-FU and IFN or 5-FU alone, being performed to analyze the pharmacokinetics and modulation of 5-FU by IFN. The maximum tolerated dose of 5-FU using this combination and a 4-hour schedule was 600 mg/m2/d for 7 days. The dose-limiting toxicity of this regimen was diarrhea. Mucositis and myelosuppression was not a marked problem at dose levels of 400 and 500 mg/m2/d for 7 days. However, at a dose level of 600 to 650 mg/m2/d for 7 days, grade 3 and 4 (WHO) leukopenia occurred in 50% and mucositis occurred in 33%. At a given dose of 5 million U, IFN did not significantly influence 5-FU serum levels. Mean steady-state serum levels of 5-FU at 500 mg/m2 given as a 4-hour infusion were 16.55 +/- 9.34 mumol/L and 18.23 +/- 12.77 mumol/L with and without IFN, respectively. Mean area under the curve (mumol/L x min) was 4,008 +/- 2,133 and 5,114 +/- 2,567 with and without interferon, respectively. Objective responses were seen in one of 17 of these heavily pretreated patients and stable disease was seen in seven of 17 patients. The recommended dose of 5-FU for use of phase II studies is 500 mg/m2/d for 7 days. We conclude that the toxicity of 5-FU plus FA with and without IFN alpha-2b can be reduced by using a 4-hour infusion instead of a bolus.

Adult↗
PubMed1991

[Value of CEA determination in follow-up of patients with liver metastasis of colorectal cancers with loco-regional chemotherapy].

The importance of carcinoembryonic antigen as a tumor marker to the follow-up of patients with liver metastases from colorectal cancer was investigated. It was reported about 29 patients receiving chemotherapy. We estimated the effect of therapy according to sonographic and computer tomographic criteria and related to the CEA-level. The correlation of the growth of cancer and the level of the CEA was positive in 81% of the patients. We do not consider as sufficient the measurement of CEA as an exclusive method for the follow-up of colorectal cancer and recommend the monthly measurement of CEA in connection with radiological examinations in the period of 3-4 month.

Adult↗
PubMed1989

[Experiences with intra-arterial tumor chemotherapy of malignant liver tumors via totally implantable catheter systems].

Locoregional chemotherapy was applied to 30 patients for isolated, surgically not removable liver tumours (13 colorectal carcinomas, 17 carcinomas on different sites). Ten patients were in Stage I, 16 in Stage II, and four in Stage III. Cytostatics were administered through totally implantable catheter systems. The following therapeutic protocol was mainly used: 5-flourouracil 800-1,000 mg/m2/3hr/die X 5 in 22 days, adriamycin 30 mg/m2/3 hr/die X 2 in 22 days. The average time of treatment amounted to ten months. Cytotoxis side effects were of minor importance. Hepatic side effects, such as chemical hepatitis or sclerosing cholangitis, were not recordable. Reduction of tumour size by 50 percent or more was recorded by computed tomography from 14 cases (46.6 percent). The objectivated rate of responsiveness in patients with colorectal carcinoma was 61.5 percent. The average period up to progression amounted to 12.1 months. Premortal spreading of the disease beyond the liver was recorded from six patients.

Antineoplastic Agents↗
PubMed1988

[Treatment of small cell bronchial carcinoma with reference to stage classification].

There are controversial views and discussions on surgical treatment of small cell lung cancer. A retrospective study covering the period from 1959 through 1983 has been conducted by the authors to analyse resective approaches to lung cancer. A total of 2,039 resections for lung cancer included operations on 354 small cell carcinomas according to the WHO nomenclature. Operations were performed on 265 cases of small cell lung cancer by the end of 1977. These were subdivided by stages, with survival rates being determined. An overall five-year survival rate was recorded from 22.8 per cent of the cases with 43.0 per cent in Stage Ia und 21.4 per cent in Stage Ib. Hence, resection of small cell lung cancer is fully supported by the authors for Stage Ia and is conditionally supported for Stage Ib, whereas complex radiotherapy and chemotherapy should be applied to small cell lung cancer in the advanced Stage II and III.

Carcinoma, Small Cell↗
PubMed1987

Pharmacokinetics of adriamycin, adriamycinol, and antipyrine in patients with moderate tumor involvement of the liver.

The pharmacokinetics of adriamycin, its metabolite adriamycinol, and antipyrine were studied in 17 patients with moderate tumor involvement of the liver and compared to that of 19 tumor patients with normal liver function (Preiss et al. 1985). The individual liver function parameters deviated from normal by a factor ranging from 2.5 to 12.2. The t1/2 alpha and t1/2 beta, the AUC (corrected for body weight and dose) and the total body clearance (CL, corrected for body weight) of adriamycin did not differ significantly between the two groups of patients. Likewise, there was no difference in the kinetic parameters of antipyrine between the two groups. Unlike adriamycin and antipyrine, adriamycinol was found to have a significantly longer t1/2term (60.5 vs 28.3 h, P less than 0.001), an increased AUC (3.00 vs 1.43 h/ug per ml, P less than 0.02), and a higher AUCadriamycinol/AUCadriamycin ratio (0.94 vs 0.52, P less than 0.02) in patients with moderate tumor involvement of the liver. The CL, the AUC, and t1/2 beta of adriamycin correlated significantly (P less than 0.001 and P less than 0.01) with the corresponding kinetic parameters of antipyrine, but not with the usual liver function parameters. No correlation could be found between the kinetic parameters of adriamycinol and those of antipyrine.

Adult↗
PubMed1987

[Problems of antineoplastic chemotherapy of pancreatic cancer].

Antineoplastic chemotherapy of pancreas carcinoma remains to be an area of intensive research. There are no convincing suggestions for far as to clinical superiority of polychemotherapy. However, combined methods seem to improve survival in cases of both advanced and surgically removed pancreas carcinoma. New, effective pharmaceuticals should be looked for in the foreseeable future. Interdisciplinary approaches will continue to be of great importance.

Antineoplastic Agents↗
PubMed1985

Plasma pharmacokinetics of adriamycin and antipyrine and its relation to the therapeutic and toxic effects.

After a simultaneous administration of adriamycin and antipyrine to 19 tumor patients, the plasma kinetics of both drugs, the therapeutic effect and the reaction to white blood cells were determined. Antipyrine was given orally at a dose of 875 mg, whereas adriamycin was administered by means of intravenous infusion for 20 min at 60 mg/m2. This application was repeated in eight patients after three weeks. Nine patients had a normal liver function. In ten patients, slight increases were found in individual liver function parameters. All patients were free from metastases of the liver and had bilirubin levels within the normal range. Antipyrine followed an open one-compartment model, whereas adriamycin followed an open two-compartment model. In the mean, t1/2 el and Cl tot of antipyrine were found to be 16.1 h and 32.9 ml/min, t1/2 beta and Cl tot of adriamycin were 23.1 h and 877 ml/min. For antipyrine and adriamycin, these parameters varied interindividually by the factors 2.8 and 3.1, respectively. No correlations were found between the liver function parameters, and the kinetic elimination parameters and the areas under the curves of both drugs. However, significant positive correlations were found to exist between t1/2 el antipyrine and t1/2 beta adriamycin and between the areas under the curves of the two drugs. A relationship between the AUC adriamycinol/AUC adriamycin ratio (which was 0.52 in the mean) and the antipyrine elimination rate did not exist. As compared to 12 persons with no response or progression, the seven patients with partial or complete response had a significantly higher AUC and a significantly lower Cl tot of adriamycin. As compared to the patients with elimination half-life values of less than 20 h, five patients with antipyrine elimination half-life values of more than 20 h had a significantly longer adriamycin elimination beta-phase and a stronger depressive effect on the white blood cells. The results obtained suggest that the antipyrine kinetics in patients with normal or slightly impaired liver function is a useful parameter for an assessment of the depression of white blood cells and the dose adjustment for adriamycin.

Administration, Oral↗
PubMed1985

[The pharmacokinetics of bendamustine (Cytostasane) in humans].

The pharmacokinetics of bendamustine (Cytostasane) was determined in plasma on seven patients after its intravenously and oral application, respectively. Cytostasane was given in a dosis of 4.2-5.5 mg . kg-1 as an intravenous infusion over 3 min and as gelatine capsules in a 7-d intervall. Its elimination from the plasma is fast, monoexponentially and two-phasic after intravenous application (t1/2 alpha = 9.6 min, t1/2 beta = 36.1 min). The AUC was 11.17 micrograms . ml-1 . h, the central distribution volume 11.15 l and the distribution volume in steady state 20.51 l. The mean total clearance was 528.9 ml . min-1. After oral application maximal plasma levels of Cytostasane were detectable before 1 h. The mean oral bioavailability was 0.57, ranged from 0.25 to 0.94. Cytostasane undergoes metabolism. Its hydrolysis in plasma is slow (t1/2 = 1.67 h). After Cytostasane the depression of leucocytes was mild.

Bendamustine Hydrochloride↗
PubMed1983

[Significance of the cell cycle for the effect of antineoplastic chemotherapy].

Cell proliferation is an essential premise for the cell-destroying action of antineoplastic chemotherapy. A survey is given on the growth behaviour of malignant neoplasms, on the cell cycle-dependent mode of action of antineoplastic chemotherapeutics as well as on the consequences of this cell kinetic knowledge for medical practice. Though research on cell kinetics of normal and tumor cell populations has yielded many useful data for the design of tumor therapy schedules in medical practice it is hitherto scarcely possible to improve selective treatment by means of cell kinetic parameters in the next future. Further investigations in normal (mainly bone marrow) and neoplastic cell populations concerning their sensitivity to cytostatic chemotherapy as well as deeper insights in molecular biological processes during the different phases of the cell cycle and subtle analyses of the growth behaviour of tumor stem cells are inevitable.

Antineoplastic Agents↗
PubMed1982

[Methodology of the colorimetric determination of alkylating cytostatics with 4-(4'-nitrobenzyl)pyridine (NBP) in plasma].

The sensitivity of the colorimetric determination of alkylating cytostatics with 4-(4'-nitrobenzyl)pyridine (NBP) has been increased by modifying procedures described in the literature. This increase in sensitivity was accomplished as follows: --Precipitation of protein with absolute ethanol at degree C; --reduction of the sample volume by evaporating the ethanol extract in a nitrogen flow; --control of the optimum pH value by means of a micro-glass electrode; --meticulously timed working under cooling in a dimmed room. The total alkylating activity and the part of endogenously activated cyclophosphamide were determined in four patients.

Alkylating Agents↗
PubMed1979

Excretion patterns of alkylating metabolites in urine following cyclophosphamide treatment of tumor patients: influence of application route, dosage, liver and kidney function.

The excretion patterns of cyclophosphamide (CP) in urine were studied in 54 tumor patients aged between 21 and 61 years, using the nitrobenzyl-pyridine (NBP) reaction, with regard to the route of application (i.v., i.m. or oral), the CP dose and the functional state of the liver and kidney. The studies were carried out in nephrectomized patients and patients with liver affections caused by the basic disease, in particular with malignant lymphomas and mammary carcinomas. The following results were obtained: 1. There exists a direct relationship between the dose of CP applied and the quantitative excretion of alkylating metabolites in urine. According to these studies in which the patients received up to 2.8 g CP/m2 body surface, the upper CP dose was limited by the generally toxic side effects rather than by the metabolization rate. 2. At comparable CP doses the route of application (i.v., i.m. or oral) has no appreciable influence on the excreted NBP activity. 3. Disorders of the liver function without signs of icterus are not a contraindication to CP treatment. 4. The functional failure of one kidney has no statistically significant influence on the excretion of alkylating metabolites in urine.

Administration, Oral↗
PubMed1978

[Hormones and cytostatic drugs in cancer chemotherapy].

From the practical experience the possibilities and the areas of application of the tumour chemotherapy and their value in the complex treatment of tumours are described. After representation of the cytostatic drugs available and description of their principal mechanism of action as well as their clinical pharmacology the indications, side-effects and contraindications for the usual cytostatic drugs are described. The possibilities of the application of the tumour chemotherapy in the clinical and out-patient field are particularly entered. Nowadays, by combinations of several cytostatic drugs and additional application of hormones satisfactory results of therapy may be achieved, which were not yet achievable 10 and more years ago. The proportion of tumours, which may be cured by chemotherapy alone, is still insignificant. The pharmacotherapy of tumours is at present put into earlier stages, e.g. into the postoperative phase as an adjuvant treatment. Finally, some practicable schemata of the therapy for solid forms of tumours are given, which are suitable for use in general practice, without putting in a claim for being regarded as therapy standards.

Antineoplastic Agents↗