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Biomedical subjects

W Scheithauer

Publications and source records attributed to W Scheithauer.

At least 163 records · Page 9Linked to original sources
PubMed1987

[Progress in experimental chemotherapy of colorectal cancer].

The aim of the present study was a prospective evaluation of the predictive value of a new system as a primary screen for cytotoxic compounds with activity against cancer of the large bowel. Basically, this system consists of three human continuous colorectal cancer cell lines that have previously been shown to manifest in vitro responsiveness consistent with that known from clinical trials. Cytotoxic drug effects are measured by use of a new semiautomated radiometric technique (Bactec system). Among 22 investigational compounds, currently being investigated in phase I or early phase II clinical trials, we found that trimetrexate, DUP-785, didemnin-B, and flavone-8-acetic acid might be effective for treatment of patients with colorectal cancer.

Antineoplastic Agents↗
PubMed1986

Recombinant interferon alfa-2C versus polychemotherapy (VMCP) for treatment of multiple myeloma: a prospective randomized trial.

Forty-two previously untreated patients with multiple myeloma were entered in a prospective, randomised trial comparing recombinant interferon alfa-2C monotherapy with VMCP (vincristin, melphalan, cyclophosphamide and prednisolone). Both treatment arms were comparable for the stratification variables such as paraprotein type, stage of disease, and renal function. Rec. interferon effected 14% responses and 29% minor responses, while 57 and 32% of VMCP-treated patients achieved a pathologically documented remission (P less than 0.001). The time on initial treatment was significantly shorter in the IFN group (3.2 months) than in the VMCP group (7.6 months). In four patients in the IFN arm, primary treatment had to be changed according to progressive or severe stationary disease. Since all four patients responded to second line therapy (VMCP) no significant difference has been observed between the two groups in survival (median follow-up greater than 12 months). Despite this clear superiority of the conventional four-drug polychemotherapy, there was some suggestion that IFN might be particularly active in cases with low tumor-burden (stage I, II), and light-chain or IgA paraprotein type.

Adult↗
PubMed1986

In vitro activity of the novel antitumor antibiotic fostriecin (CI-920) in a human tumor cloning assay.

A human tumor cloning assay was utilized to evaluate the antineoplastic activity of the novel antitumor antibiotic fostriecin (CI-920). Initial screening with 10.0 mcg/ml continuous exposure against a variety of histologic tumor types resulted in 14/51 (27%) in vitro responses (defined as greater than 50% decrease in TCFUs). Further investigation of the compound was performed in 1-hr preincubation experiments. The in vitro response rate at a concentration of 1.0 mcg/ml (which was considered to correspond to a clinically achievable concentration) was 15/43 (35%). Response rates for specific tumor types included: 5/15 in ovarian cancer, 5/12 in breast, and 4/11 in human lung cancer. The impression of significant antitumor activity of the compound at this dose was further substantiated by comparing its in vitro activity with a variety of simultaneously tested standard anticancer agents. In addition, these data indicated the possibility of non-cross resistance of CI-920 to several established cytostatics. CI-920 is a compound with good in vitro activity which should be further developed for clinical trials.

Alkenes↗
PubMed1986

Direct effects of the hypoxic cell sensitizer misonidazole on colony formation in a human tumor cloning assay.

The human tumor cloning assay as described by Hamburger and Salmon was utilized to study the direct antitumor effects of the hypoxic cell sensitizer misonidazole (MISO). Cells from 106 tumor specimens directly obtained from patients were exposed to MISO at clinically achievable drug concentrations (0.5 mM). Of 30 evaluable tumors, seven specimens (23%) showed a less than or equal to 50% decrease of TCFU's. In vitro sensitivity to MISO was noted in human breast cancer, renal cancer, non small-cell lung cancer, and adenocarcinoma of unknown primary site. A dose response relationship was demonstrated in a subset of experiments including 6 patient's tumors and one human breast cancer cell-line. An analysis relating MISO sensitivity or resistance to the results obtained with other, simultaneously tested standard anticancer drugs indicated that tumors exhibiting a less than or equal to 50% decrease of TCFU's in the presence of MISO were also likely to be sensitive to other cytotoxic drugs. In summary, our data suggest that the 'nitroimidazoles' may exert clinically significant direct antitumor effects in individual tumors. The human tumor cloning assay may have potential to evaluate these direct effects of MISO-analogues and other new radiosensitizers currently being tested in clinical trials.

Antineoplastic Agents↗
PubMed1986

[Prognosis of malignant tumors of the exocrine pancreas: effect of clinical and pathologico-anatomic variables on patient survival].

Survival patterns of 112 patients with histologically ascertained pancreatic cancer were analysed retrospectively in an attempt to determine the relationship to various clinical and pathologic-anatomic prognostic factors. Stage of disease, localisation of the primary tumor, as well as histologic grade were found to influence the patient's survival significantly. A limited anatomic involvement with tumor, localisation within the head of the pancreas, and high-grade differentiation were associated with an increased median survival. An evaluation of non-anatomic prognostic variables suggested a relative survival advantage for females, younger age groups, patients with favourable initial performance status and short symptom duration. There was no obvious relationship between survival and qualitative or quantitative indication of weight loss. In order to permit a critical evaluation of the value of any treatment program in pancreatic cancer, our observations reemphasize the need to define characteristics of patients under study.

Adult↗
PubMed1986

New screening system for selection of anticancer drugs for treatment of human colorectal cancer.

We report an evaluation of a new radiometric technique (BACTEC assay) as a potential screening system for cytotoxic compounds with activity against cancer of the large bowel. Exponentially growing cells of nine different human colorectal cancer cell lines were exposed to a variety of standard anticancer agents with or without documented clinical activity. Each drug was tested in a series of 1-h and continuous exposure studies utilizing three different concentrations. Antineoplastic effects were analyzed as a function of in vivo achievable serum concentrations, namely by a ratio of the concentration required to decrease cell growth to 10% of control to one-tenth of the peak plasma concentration in humans. Our results suggest that COLO 320DM, OM-1, and Ht-29 cells manifest responsiveness to anticancer drugs consistent with that noted in clinical studies with most agents tested. The radiometric technique provides several advantages for a screening system, including reproducibility, a good agreement with the cloning assay, speed, and low costs. The combined use of the BACTEC technique and the three colon cancer cell lines could prove useful as a screen for new anticancer compounds with activity in colorectal cancer.

Antineoplastic Agents↗
PubMed1986

Shortened platelet half-life in multiple myeloma.

Various defects in platelet function have been reported as being associated with multiple myeloma. In 30 myeloma patients and 15 healthy controls, we investigated platelet survival using in vitro labeling of autologous platelets with 111indium-oxine and measuring the in vivo kinetics of the radioisotope. Significantly shortened platelet half-life in patients averaged 73 hours, while platelet half-life in the healthy controls averaged 107 hours. In myeloma patients, serum levels of thromboxane B2, beta-thromboglobulin, and platelet factor 4 were significantly elevated; aggregation indices were within the pathological range; platelet counts and spleen-liver indices, however, were comparable to those of the healthy control group. No statistical correlation was found between platelet half-life and paraprotein concentrations. Our findings suggest an initial--so far unexplained--intravascular process of platelet activation and consumption that finally manifests in shortened platelet half-life. It seems that overt thrombocytopenia develops only when the compensatory capacity of the bone marrow finally becomes exhausted. Further studies should be able to elucidate the pathophysiologic processes involved.

Blood Platelets↗
PubMed1986

Model for estimation of clinically achievable plasma concentrations for investigational anticancer drugs in man.

A major problem related to in vitro testing of new investigational anticancer compounds is the lack of accurate pharmacokinetic data for the drugs in man. Based on the concept of a relationship between certain toxicologic endpoints in animal systems and maximally tolerated doses in man, we hypothesized that a comparable agreement might exist between these experimental animal toxicology data and clinically achievable peak plasma concentrations (PPCs). A retrospective analysis of the known data pairs of 28 commonly used cytotoxic compounds supports the existence of a reasonably good correlation between ip LD50 values (Pearson test) in nontumored mice and PPCs in man (r2 = 0.501; P less than 0.0001). Our data suggest that by use of the resultant statistical regression model a rational starting point can be selected for in vitro screening of entirely new agents for which human PPCs are not available. Additionally, application of this approach may also prove useful in relation to selecting in vitro doses for chemosensitivity assays intended for predictive correlation with clinical response in cancer patients.

Animals↗
PubMed1985

In vitro phase II trial of recombinant interferon alpha-2 in gastrointestinal cancer.

The antitumor effects of recombinant interferon alpha-2 (rIF) on clonogenic tumor cells were investigated in 29 cases of gastrointestinal cancer. An in vitro response (greater than or equal to 50% inhibition of tumor colony-forming units) was observed in 17% of the tumors, including 2 of 8 pancreatic, 2 of 6 gastric, and 1 of 10 colon cancer specimens. The relative efficacy of rIF in tissue cultures of pancreatic and gastric tumors was further substantiated by the resistance against simultaneously tested single conventional cytostatic drugs. Preliminary results of comparative studies of cloned interferon alpha-2 and human purified leukocyte interferon (hlIF) in 2 human colon cancer cell lines and 11 fresh tumor specimens suggest similar trends in terms of colony inhibition in individual assays. However, the interpatient differences indicate an overall superiority of the natural preparation (P less than 0.02).

Antineoplastic Agents↗
PubMed1985

Acute encephalopathy associated with continuous vincristine sulfate combination therapy: case report.

Neurotoxicity is a well-recognized and commonly observed side effect associated with the use of vincristine sulfate in cancer chemotherapy. The clinical manifestations of vincristine neuropathy cover a wide spectrum of peripheral neurologic dysfunctions that have been described to be reversible and cumulative in most instances (1, 2). Paresthesias, loss of tendon reflexes, and progressive weakness are the most common clinical features (3, 4). Sensory impairment, cranial nerve palsies, gastrointestinal disturbances, and autonomic dysfunctions including atonic bladder, impotence, and orthostatic hypotension may occur (5). Acute CNS complications, usually presenting as generalized seizures, are extremely rare and only a few cases have been reported which were without underlying biochemical or structural abnormalities (1, 5-9). We describe the case of a woman with multiple myeloma, who developed fulminant encephalopathy following 4 days of continuous vincristine, adriamycin, and day 1-4 pulse dexamethasone (VAD) combination therapy.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1985

Weekly low dose doxorubicin monotherapy in metastatic breast cancer resistant to previous hormonal and cytostatic treatment.

Weekly low dose doxorubicin monotherapy was evaluated in heavily pretreated patients with metastatic breast cancer. 19 patients received 8-12 mg/m2 doxorubicin/week for a treatment period of up to 7 months until a progression of the disease occurred (mean number of weekly courses 15 +/- 8). In 2 of 17 evaluable patients, an objective response with a duration of 3+ and 5 months respectively was achieved. In 9 patients a stabilisation of the disease was observed (mean duration of DS 4 mos +/- 2), whereas the disease progressed in 6. The tolerance for this regimen was remarkable, with neither serious acute toxicity nor any signs of congestive cardiomyopathy even in those patients who were treated beyond a cumulative dose of 450 mg/m2. Weekly low dose doxorubicin monotherapy shows modest activity, but is devoid of severe toxicity in heavily pretreated patients with metastatic breast cancer. An increase in the therapeutic index was not observed.

Aged↗
PubMed1985

CADIAG: approaches to computer-assisted medical diagnosis.

CADIAG-1 is a medical expert system, based on a symbolic logic representation of medical relationships. Strong relationships such as confirming, excluding or obligatory occurrence are applied to confirm or exclude diagnoses. Weak relationships are represented by facultative and not confirming relationships (FN-relationships). Diagnostic hypotheses are established by systematic combination of symptoms showing FN-relationships. CADIAG-2, a medical expert system based on fuzzy set theory and fuzzy logic, allows detailed specification of medical relationships. Here the diagnostic process also provides confirmed and excluded diagnoses as well as diagnostic hypotheses. Hypotheses are calculated by considering fuzzy relationships between medical entities. 426 cases with rheumatic and 47 cases with pancreatic diseases were tested. For CADIAG-1, the overall accuracy for confirmation and hypothesis generation is calculated with 91.1% for rheumatic diseases and 100% for pancreatic diseases. CADIAG-2 reached an overall accuracy of 93.7% for rheumatic cases and 91.5% for pancreatic cases.

Artificial Intelligence↗
PubMed1985

Phase I study of recombinant human interferon alpha-2C in patients with chemotherapy-refractory malignancies.

Twenty-two patients with advanced haemopoietic and other malignancies were treated intramuscularly with recombinant interferon-alpha 2C in a daily escalating dose. The most common side-effects were flu-like symptoms. Two patients showed severe neurotoxicity, which was completely reversible in 1 case. Doses above 30 X 10(6) IU/day were poorly tolerated and could only be achieved in a minority of the patients. Objective tumour responses were documented in malignant lymphomas, hairy cell leukaemia, and renal cell carcinoma.

Adult↗
PubMed1985

Treatment with recombinant interferon-alpha-2C: multiple myeloma and thrombocythaemia in myeloproliferative diseases.

Forty-two patients with multiple myeloma were allocated to two groups to receive either polychemotherapy with vincristine, melphalan, cyclophosphamide and prednisolone, or recombinant interferon-alpha 2C monotherapy. The response rate of 43% in the interferon group was significantly lower than that in the chemotherapy group (89%). Patients with stage I disease showed better response rates than those with stage II or stage III disease. Eleven patients with thrombocythaemia due to polycythaemia vera, chronic myeloid leukaemia or essential thrombocythaemia were treated with recombinant interferon-alpha 2C and complete remissions were achieved in 7 of the 8 evaluable patients. Side-effects were common on interferon therapy, but could be reduced by dose reduction and were reversed by cessation of treatment.

Adult↗
PubMed1985

[Interferon in the treatment of multiple myeloma].

The effect of recombinant interferon-alpha-2C monotherapy was compared with the efficacy of VMCP-polychemotherapy in 42 patients with multiple myeloma in a prospective randomized multicenter trial. IFN-treatment induced remissions (R) in 2 (14%) and partial remissions (PR) in 4 (29%) out of 14 evaluable patients. 7 patients remained stable. Polychemotherapy induced R in 11 (57%) and PR in 6 (32%) of 19 evaluable patients. 2 (11%) patients remained stable. IFN was preferentially active in patients with low tumor burden and patients with IgA paraprotein. The proportion of responders (R + PR) was significantly lower in the IFN-arm (43%) compared to the polychemotherapy group (89%; p less than 0,001).

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1985

[Interferon (IFN) therapy (recombinant IFN-alpha-2C or recombinant IFN-gamma) in metastasized hypernephroma].

Recombinant interferon-alpha-2C (rec. IFN alpha-2C) and recombinant interferon-gamma (IFN-gamma) was studied in 12 patients with metastasized renal cell carcinoma. 8 patients were treated with IFN-alpha-2C: 1 patient achieved a complete remission, 2 patients showed mixed responses, and 2 had stabilisation of their disease. In 3 patients progressive disease was observed. IFN-gamma was studied in 4 patients; 2 patients showed stable and 2 progressive disease. Side effects of IFN-alpha treatment included influenza-like symptoms, moderate hematological toxicity and neurological symptoms. During treatment with IFN-gamma similar side effects were observed, although fever generally was more pronounced. All symptoms ceased after dosis reduction or discontinuation of treatment.

Adult↗