PubMed Health⌕ Search

Biomedical subjects

W Scheithauer

Publications and source records attributed to W Scheithauer.

At least 127 records · Page 7Linked to original sources
PubMed1991

Biotransformation and in vitro activity of an arabinosylcytosine 5'-chloro-5'-deoxy analog.

5'-Chloro-5'-deoxyarabinosylcytosine (5'-chloro-araC), a lipophilic and cytidine-deaminase resistant analog of the cytotoxic agent arabinosylcytosine (araC) was evaluated in terms of bioactivation, transformation and its cytotoxic activity in vitro. 5'-Chloro-araC interferes with DNA synthesis (IC50 = 2.8 mumol/l) and inhibits the growth of L1210 cells in suspension culture (IC50 = 1.05 mumol/l) and in the soft agar assay (IC50 = 0.65 mumol/l). Being phosphorylated to the triphosphate of araC-araCTP (5'-triphosphate of araC), 5'-chloro-araC has the same mechanism of action as arabinosylcytosine. In alkaline solutions 5'-chloro-araC is transformed to another (cytostatically inactive) araC analog--2',5'-anhydroarabinosylcytosine--but at physiological pH and temperature conditions, it has sufficient stability to be phosphorylated and thus activated. A lower rate of araCTP formation from 5'-chloro-araC explains the somewhat lower cytotoxic effect of this compound against various established cell lines in vitro compared to araC. Lipophilicity that would allow an oral drug formulation and certain other superior physico-chemical and biochemical characteristics of 5'-chloro-araC make this compound an interesting candidate for further investigations.

Animals↗
PubMed1991

Interferon in essential thrombocythaemia.

In the present investigation, 20 patients with ET were treated with recombinant interferon alfa-2c (IFN) for up to 4 years. Initially, IFN was administered subcutaneously at a dosage of 6-45 MU/week. The dosage was adjusted according to individual tolerance and response. The median dose during induction was 20 MU/week, 10 MU/week during the remaining first year, 6 MU/week during the second year and 2 MU/week thereafter. 13 patients (65%) achieved complete remission (platelet count less than 440/nl), four patients (20%) had partial remission (greater than 440/nl but a reduction by more than 50% of the initial count). The median platelet count remained steady throughout the 4-year period of treatment, in spite of extreme dose reductions. After withdrawal of IFN, however, platelet counts again increased. The white blood cells showed a marked decrease similar to that of platelet counts, whereas the haemoglobin level remained fairly stable. In the bone marrow, a significant decrease in megakaryocyte density and size could be observed. Concurrently with the improvement of haematological parameters, clinical symptoms improved, but reappeared after withdrawal of IFN. During induction, fever, bone and/or muscle pain, fatigue, lethargy and psychological symptoms were the most prominent side-effects in the majority of patients. In three patients these symptoms led to discontinuation of the treatment. With repeated dose reductions, excellent long-term tolerance was achieved, and during late maintenance treatment the only observed side-effect was an induction of thyroid autoimmunity in three patients. IFN is an effective, well-tolerated alternative in the long-term treatment of symptomatic ET. However, since withdrawal of IFN leads to recurrence of thrombocytosis, continued treatment is to be recommended.

Adult↗
PubMed1991

[5-Fluorouracil (5-FU)/leucovorin in comparison to other current chemotherapy protocols in metastasizing colorectal carcinoma].

17 patients with metastasizing colorectal cancer were treated in a phase II-study with systemic intravenous chemotherapy (Petrelli N, Proc ASCO 286, 1987) consisting of leucovorin 500 mg/m2 in a 2 hr infusion and 5-fluorouracil (5-FU) 600 mg/m2 bolus one hour after the commencement of the leucovorin infusion. Limiting toxicities were gastrointestinal, in form of nausea/vomiting of WHO grade 3 (n = 1) and of diarrhoea of maximal grade 4 (n = 5), as well as haematological with a maximal nadir of leucocytes of WHO grade 4 (n = 1) and of thrombocytes of WHO grade 1 (n = 1). Of the 14 evaluable patients an objective response was achieved in 21% of cases (CR: n = 1, PR: n = 2). 64% of the patients showed no change and 14% showed progression of their disease, 7 out of the 17 patients have died; the median survival was 24 months. With respect to objective remission, our result of 21% response rate is lower than the median of 32% of 24 different studies comprising 695 patients; nevertheless, the present response rate is within the range observed in the published studies of between 0% and 67%. In order to estimate the antitumoral efficacy of the new regimen 5-FU/leucovorin more objectively, a retrospective comparison of the therapy regimens used most frequently in disseminated colorectal cancer (5-FU monotherapy, 5-FU/methotrexate (MTX), 5-FU/MTX/low dose leucovorin, 5-FU/cisplatin, 5-FU/leucovorin) has been performed. The continuous administration of 5-FU monotherapy, with an objective response rate of 26%, was superior to standard 5-FU monotherapy as a bolus injection or short-term infusion.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1990

Pirarubicin (4'-o-tetrahydropyranil-adriamycin) for treatment of advanced breast cancer. A Clinical Phase II study.

In a phase II study, 77 patients with metastatic breast cancer were treated with pirarubicin, 70 mg/m2 iv every 3 weeks. Most of them had received prior hormonal (n = 39) and/or chemotherapeutic drug treatment for advanced disease, including anthracycline-containing regimens in 17. After a median of 5.5 treatment cycles (range 1-14), objective tumor response was seen in 22/71 (31%) evaluable patients (4CR, 18 PR). Stable disease occurred in 34 (48%) patients, whereas the tumor progressed in 15 (21%). Significant hematologic toxicity (WHO grade III-IV) requiring interval and/or dose adjustments was observed in 41 (58%) patients. Other treatment-related side effects were generally mild, and included alopecia in 52 (73%), nausea and/or emesis in 50 (70%), and stomatitis and diarrhea in 3 patients each. There was no treatment-related death, nor was there any evidence of cardiac toxicity thus far. In summary, the early results of this trial suggest that pirarubicin is an active and rather well tolerated drug in pretreated patients with advanced breast cancer.

Adult↗
PubMed1990

Sequential high-dose methotrexate, 5-fluorouracil, and doxorubicin for treatment of advanced pancreatic cancer.

A phase II trial of sequential high-dose methotrexate, 1500 mg/m2, and 5-fluorouracil, 1500 mg/m2 intravenously on day 1, plus doxorubicin, 30 mg/m2 i.v. on day 14, has been undertaken in patients with locally advanced or metastatic adenocarcinoma of the pancreas. Of 25 evaluable patients there were 1 complete response and 3 partial responses for an overall response rate of 16% (95% confidence interval 5%-36%). The median survival of all patients was 6.7 months (range 1-17 months). There was one treatment-related death due to pancytopenia and sepsis. In all other patients therapy was generally well-tolerated. We conclude that this combination protocol has only modest activity in the treatment of advanced pancreatic cancer.

Adult↗
PubMed1990

Effect of recombinant interferon-alpha2C on reticuloendothelial function in patients with thrombocytosis.

The aim of the study was to investigate the influence of recombinant interferon-alpha 2C (rIFN-alpha 2C) on the in vivo Fc-dependent phagocytic activity of the reticuloendothelial (RE) system. Fourteen patients with excessive thrombocytosis due to myeloproliferative disorders were studied before and 3 months after initiation of therapy. RE function was determined by measuring the clearance of autologous red blood cells (RBC) labeled with 51Cr and sensitized with anti-D antibody. Eleven of the 14 patients responded to rIFN-alpha 2 treatment (platelets, less than 440 X 10(9)/liter). Rather in contrast to a shortening of platelet half-life and an increase (trendwise) in platelet-bound IgG, rIFN-alpha 2 caused a significant impairment of RE function. Although this finding could in part be accounted for by the treatment-related decrease in splenic volume, statistical analysis revealed a direct influence of rIFN-alpha 2 on RBC clearance (p less than 0.01). Our study results might be explained by an interferon (IFN)-induced, intensified expression of Fc receptors on platelet (and leukocyte) surfaces, possibly enhancing unspecific binding of IgG to their cellular membranes. The subsequent increased platelet uptake may lead to an overloading of the RE system causing impaired reactions to additional stimuli such as IgG-coated RBC.

Aged↗
PubMed1989

[Gestagen receptor-positive, solid-cystic acinar-cell tumor of the pancreas].

In a 16-year-old girl with left upper abdominal pain of two months' duration fine-needle biopsy (guided by computed tomography) revealed a solid-cystic acinar-cell tumour of the pancreas. The tail of the pancreas was resected and the spleen removed. On inspection, the tumour--about 9 cm in diameter--was encapsulated and consisted of soft, brownish, partly haemorrhagic tissue. Histologically and immunohistochemically the diagnosis of an acinar-cell tumour was confirmed. Analysis of steroid hormone receptors revealed a high progestogen content. Since the operation the patient has remained symptom-free without any sign of tumour recurrence.

Adolescent↗
PubMed1989

Serological screening for a mucine-like carcinoma-associated antigen (MCA) in patients with gastrointestinal tract malignancies.

Mouse monoclonal antibody b-12 identifies a high-molecular-mass glycoprotein antigen strongly expressed by breast carcinoma cells. Since immunohistochemical studies have also demonstrated some reactivity with other epithelial neoplasms, and since "mucine-like carcinoma-associated antigen" (MCA) has gained considerable interest as a tumor marker in breast cancer, we have investigated 34 patients with histologically proven advanced gastrointestinal malignancies for the presence of elevated MCA serum levels. Our data suggest that screening for and/or monitoring of MCA in these tumors is unlikely to have any practical clinical relevance. The possible role of MCA as a marker in tissue specimens for abortive adenomatous differentiation in gastrointestinal (and other) neoplasms, however, remains to be determined.

Antigens, Neoplasm↗
PubMed1989

Alpha-fetoprotein-positive adenocarcinoma of the pancreas.

A case of a poorly differentiated ductal adenocarcinoma arising in the body and tail of the pancreas with diffuse intraabdominal metastases in an adult is reported. Serum alpha-fetoprotein (AFP) level was markedly elevated in this patient, but fell transiently when a partial tumor response to combination chemotherapy was achieved. Both the occurrence of biochemical and anatomical responses, and the immunohistochemical finding of AFP in the tumor tissue clearly indicate that oncofetal protein is produced by the tumor cells. The patient survived 10.5 mo after the onset of symptoms.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1989

Performance evaluation of medical expert systems using ROC curves.

This paper presents a performance evaluation of the diagnostic accuracy of the medical expert system CADIAG-2/PANCREAS. The study included 47 clinical cases from a university hospital with 51 diagnosis of pancreatic diseases (four patients had two pancreatic diseases). As gold standard, the histologically or clinically confirmed diagnoses were assumed. Performance was studied along three lines: (a) each case was evaluated twice, first, by restricting patient data to history, physical examination, and basic laboratory tests and, second, by utilizing the complete set of data including also special laboratory tests. US. X ray, CT-scan, ECG, and biopsy, if available: (b) considering CADIAG-2's hypotheses generation, each evaluation series was also carried out twice, first, by testing whether the gold standard was the first diagnosis in the ranked list of hypothesis and, second, whether the gold standard was among the hypotheses: (c) receiver operating characteristic (ROC) curves were determined by varying an internal threshold which determined the extent of CADIAG-2's diagnostic hypotheses generation. The evaluation showed that CADIAG-2's initial list of diagnostic hypotheses, based on patient history, physical examination, and basic laboratory tests usually has already included the gold standard diagnosis and thus an application of CADIAG-2 at a very early stage of the diagnostic process seems achievable. Moreover, it turned out that given the complete set of patient's medical data the gold standard is usually ranked at the first place in the list of hypotheses. except for patients with chronic diseases where only unspecific findings are available. The last test series showed that ROC curves do not only allow optimal adjustment of the expert system's internal ad hoc decision criteria such as thresholds, weights, and scores but also provide a basis for better comparing the performance of different medical expert systems.

Diagnosis, Computer-Assisted↗
PubMed1989

VMCP chemotherapy with or without interferon-alpha-2 in newly diagnosed patients with multiple myeloma.

Fifty-two previously untreated patients with multiple myeloma were randomized to either a combination of recombinant interferon (rIFN) alpha-2 and chemotherapy or chemotherapy alone. Patients were treated with vincristine, melphalan, cyclophosphamide and prednisolone every 4-6 weeks. In the combined treatment arm rIFN was administered concurrently with chemotherapy as well as during chemotherapy free intervals. The combined regimen effected 17/21 (80.9%) responses as compared to 19/27 (70.4%) responses in VMCP treated patients. Addition of rIFN to chemotherapy did not enhance hematologic toxicity. These findings suggest a somewhat higher rate of objective response in the VPMC + rIFN group, although a significant improvement in median survival by adding rIFN to conventional first line polychemotherapy in myeloma patients has not yet been achieved.

Adult↗
PubMed1989

Application of a new radiometric system for identification of potentially useful drug combinations for treatment of human gastrointestinal adenocarcinoma.

As an alternative to empirical clinical evaluation of combined drug effects in human tumors, and in an attempt to establish whether the combination of mitoxantrone (DHAD) with other standard drugs would be of any benefit to the patient with advanced gastrointestinal cancer, we have examined the results of simultaneous single-agent testing in vitro in a panel of 8 human colorectal (HCC) and 5 gastric cancer (HGC) cell lines. Cytotoxic drug effects were measured by the use of a new semiautomated radiometric technique (Bactec system), and were quantitated with attention to potentially clinically relevant plasma concentrations. Among several different drug combinations tested, maximal synergistic cell kill was found for DHAD + 5-fluorouracil; continuous incubation of the cells at 1/100 of the peak plasma concentration achievable in humans yielded in vitro responses in 8/8 HCC and 5/5 HGC cell lines. With regard to our results of single-agent testing, our finding of a significant level of in vitro arabinoside-C activity, using prolonged exposure at an in vitro dose corresponding to a clinical high-dose regimen, may provide a rational basis for (re)evaluation of the compound in gastrointestinal cancer patients.

Adenocarcinoma↗
PubMed1989

Phase II evaluation of 5-fluorouracil, folinic acid and cisplatin in advanced-stage colorectal adenocarcinoma.

Twenty-seven patients with advanced measurable colorectal carcinoma were treated with a combination protocol consisting of folinic acid (FA) 200 mg/m2 i.v. bolus followed by 5-fluorouracil (5-FU) 550 mg/m2, and cisplatin (CIS) 20 mg/m2 each administered as a 2-hour i.v. infusion. Treatment was given on 4 consecutive days at 3- to 4-weekly intervals. Of 25 evaluable patients, 1 achieved complete remission and 5 partial remission for an overall response rate of 24%, while 9 patients (36%) had stable disease. Two out of 6 responders had previously progressed on 5-FU-containing regimens. The 95% confidence interval for response is 7-41%. Median survival time for all 27 patients enrolled in the study is 27+ weeks. Tolerance was remarkable and consisted primarily of mild and reversible gastrointestinal symptoms and myelosuppression. This 3-drug-regimen had significant palliative activity in our patient population. Its definitive role in the treatment of metastatic colorectal cancer as well as the potential improvement of the therapeutic index of 5-FU/FA by addition of CIS, require further evaluation in a randomized phase III trial.

Adenocarcinoma↗
PubMed1989

Combined alpha-2C-interferon/VMCP polychemotherapy versus VMCP polychemotherapy as induction therapy in multiple myeloma: a prospective randomized trial.

Thirty-three previously untreated patients with multiple myeloma were randomized to either a combination of recombinant interferon-alpha-2C (rIFN-alpha-2C) plus vincristine/melphalan/cyclophosphamide and prednisone (VMCP) or VMCP chemotherapy alone. The combined regimen effected 67% responses and 26% minor responses, while 35 and 47% of VMCP-treated patients had a pathologically documented remission, respectively. Despite the somewhat earlier achievement and duration (12.0 vs. 8.0 months) of objective response, and the marginal survival benefit observed in the rIFN-alpha-2C + VMCP treatment arm, a significant improvement in therapeutic gain by adding a biologic response modifier to conventional first-line polychemotherapeutic drug treatment in myeloma patients has not yet been achieved. The combined regimen was well tolerated without unusual or unexpected toxic effects.

Adult↗
PubMed1988

Application of a new preclinical drug screening system for cancer of the large bowel.

We report a prospective evaluation of three human, continuous colorectal cancer cell lines and a new semiautomated radiometric technique (Bactec system) as a primary screening procedure for cytotoxic compounds with activity against cancer of the large bowel. COLO 320DM, Ht-29, and the metastatic OM-1 colon cancer cell line that have previously been shown to yield clinically relevant information in terms of drug sensitivity patterns in humans were all tested against 11 new compounds currently being investigated in phase I or early phase II clinical trials. Our results suggest that trimetrexate, DUP-785, didemnin B, and flavone-8-acetic acid may be clinically effective for the treatment of colorectal cancer.

Colonic Neoplasms↗