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Biomedical subjects

W Scheithauer

Publications and source records attributed to W Scheithauer.

At least 127 records · Page 7Linked to original sources
PubMed1993

MDR1 gene expression in primary colorectal carcinomas.

The expression of the MDR1 gene, a multidrug resistance gene, was prospectively determined in 113 primary colorectal carcinoma specimens and correlated with clinical data including survival durations of the patients. MDR1 RNA was detected in 65% of the carcinomas. No expression of the MDR2 gene was seen, MDR1 gene expression was independent of age and sex of the patients, size and histologic grading of the tumour, lymph node involvement and distant metastasis. Kaplan-Meier analysis revealed that the durations of both relapse-free survival and overall survival were not different between patients with MDR1 RNA positive tumours and those with MDR1 RNA negative tumours.

Adenocarcinoma↗
PubMed1993

[Progress in adjuvant and palliative chemotherapy of colorectal cancer: current status and perspectives].

After 3 decades of intense investigation some important advances have been made in the management of patients with colorectal cancer. Adjuvant chemotherapy trials in colon cancer have indicated a significant decrease in recurrence and a prolongation of survival when 5-fluorouracil (5-FU) plus levamisole are administered to patients with potentially curable tumour which has, however, spread to locoregional lymph nodes. Recent trials in stage II and III rectal cancer have demonstrated a comparable advantage for postoperative adjuvant 5-FU combined with radiation therapy. In the setting of metastatic disease, both in the presence and absence of clinical symptoms, it seems also likely that certain palliative regimens integrating biochemical modulation of 5-FU will result in a survival benefit without affecting the quality of life. According to continuing worldwide, interdisciplinary and cooperative study efforts, further improvements in current standard treatment approaches are likely to be achieved in the near future.

Antineoplastic Agents↗
PubMed1992

A phase II trial of 5-fluorouracil, leucovorin, and recombinant alpha-2b-interferon in advanced adenocarcinoma of the pancreas.

BACKGROUND: Preclinical and clinical data suggest that both leucovorin (LV) and interferon (IFN) can augment the cytotoxic effects of 5-fluorouracil (5-FU). Based on the rationale of biochemical double modulation, the current Phase II study was undertaken. METHODS: Thirty-two previously untreated patients with advanced adenocarcinoma of the pancreas were treated with subcutaneous recombinant alpha-2b-IFN at a dose of 10 million units on 3 consecutive days; LV (200 mg) plus 5-FU (20 mg/kg) were administered as intravenous bolus doses on day 3. Treatment courses were repeated as tolerated in 2-to-3-week intervals, depending on the patient's complete blood count. RESULTS: Of 32 evaluable patients, 4 (12.5%) had a partial response (95% confidence limit, 4-30%) of 4, +6, 7.5, and 9 months' duration, and 13 (40.5%) had stable disease. The median duration of survival for all patients from the start of therapy was 5.5 months. The most common toxicities observed were IFN-related fever during the first course (69%), mild leukopenia (53%), and gastrointestinal symptoms (28%). CONCLUSIONS: Although the combination of 5-FU, LV, and recombinant alpha-2b-IFN in patients with advanced pancreatic adenocarcinoma has some activity and generally was well tolerated, the observed response rate and median survival were not superior to 5-FU monotherapy.

Adenocarcinoma↗
PubMed1992

Liver function in acute viral hepatitis as determined by a hepatocyte-specific ligand: 99mTc-galactosyl-neoglycoalbumin.

Twelve patients with recently diagnosed acute viral hepatitis underwent serial 99mTc-galactosyl neoglycoalbumin scanning of the liver (for up to 8 mo). Injection of 99mTc-galactosyl neoglycoalbumin (150 mBq) at a rate of 3.5 mg (50 nmol; 1 ml) revealed that the liver is the exclusive site of tracer uptake. Simulation of 99mTc-galactosyl neoglycoalbumin kinetics allowed quantification of galactosyl neoglycoalbumin binding to human hepatic binding protein. Return of liver function test scores to normal values was associated in two patients with hepatitis A, in four patients with hepatitis B and in two patients with non-A, non-B hepatitis virus infection, with increases in hepatic binding protein concentration (up to three times the initial concentration), binding rate constant and hepatic blood flow. In the other four patients (three patients with hepatitis B and one patient with cytomegalovirus infection) a prolonged course of disease was monitored. In the mean, hepatic binding protein increased from 0.41 +/- 0.11 mumol/L after onset of acute hepatitis (n = 12) to 0.78 +/- 0.21 mumol/L after 6 mo of follow-up (n = 10) (p less than 0.001). During this period, binding rate constant (72.4 +/- 12.6 vs. 82 +/- 11.5 mumol/L/sec; p less than 0.05) and hepatic blood flow (0.027 +/- 0.0051 vs. 0.031 +/- 0.0083 L/sec; p less than 0.05) increased. Hepatic binding protein concentration correlated highly with actual laboratory test results for liver function (r = 0.98; p = 0.0001). We conclude that scintigraphic evaluation of functional liver cell mass using the new receptor-tracer 99mTc-galactosyl neoglycoalbumin could provide an in vivo diagnostic means of quantifying liver function and assessing liver morphology. In addition, our findings suggest that changes in hepatic binding protein-receptor concentration are likely to occur in vivo.

Acute Disease↗
PubMed1992

Comparative analysis of CA72-4, CA195 and carcinoembryonic antigen in patients with gastrointestinal malignancies.

To establish further the clinical significance of the novel quantitative immunoradiometric assay system CA72-4 in patients with gastric and other digestive tract malignancies, the sera of a total of 208 subjects have been analysed and levels of carcinoembryonic antigen (CEA) and another promising new tumour marker, CA195, have been compared. Twenty patients had gastric (GC), 60 colorectal (CC), and 14 pancreatic carcinomas (CC); 94 patients had benign disorders, and 20 were healthy volunteers. CA72-4 elevations above normal (greater than 4 U/ml) were observed in 6 (30%) GC, 17 (28%) CC, and 8 (57%) PC patients. CA195 appeared more sensitive and was increased (greater than 10 U/ml) in 35% GC, 70% CC, and in 100% PC patients; CEA levels above normal (greater than 5 ng/ml) were noted in 35%, 45%, and 66% of patients respectively. CA72-4 had a rather high specificity and was increased in only 6/94 (6%) patients with benign diseases, whereas CA195 had a false positive rate of 23%, and CEA of 33%. Among 20 healthy donors, none had elevated levels of CA72-4 or CA195, but marginal elevations of CEA were noted in 3 smokers. Despite some advantage of the new tumour marker CA72-4 in terms of specificity, its value as a serodiagnostic test in gastrointestinal cancer patients seems inferior to that of CA195 and CEA.

Antibodies, Monoclonal↗
PubMed1991

Treatment of patients with advanced colorectal cancer with cisplatin, 5-fluorouracil, and leucovorin.

Based on in vitro studies that have demonstrated synergy between 5-fluorouracil (5-FU), leucovorin (LV), and cisplatin (CDDP) against human colon cancer cell lines, a clinical trial was initiated to determine the effects of this combination in patients with advanced unresectable colorectal carcinoma. Fifty-nine patients were enrolled in the study and 12 of them had received prior conventional 5-FU chemotherapy. Treatment consisted of 4 weekly courses of high-dose LV (200 mg/m2) administered by intravenous (IV) bolus, followed by 5-FU (550 mg/m2) and CDDP (20 mg/m2) each administered as a 2-hour infusion on 4 consecutive days. After a median of 5.5 treatment cycles, objective tumor response was seen in 20 of 59 patients (34%) (this included 3 complete remissions). The response rate in the 47 previously untreated patients was 38% (95% confidence limits, 26% to 53%). Stable disease occurred in 16 (27%) patients, whereas the tumor progressed in 23 (39%) patients. The median survival time was 11.5 months, with 15% of the patients alive at 2 years. The regimen was well tolerated and the primary side effects were mild and reversible gastrointestinal symptoms and myelosuppression. There was no episode of life-threatening toxicity. Eastern Cooperative Oncology Group (ECOG) Grade III adverse reactions that required 25% dose reductions occurred in only 14% of the patients. The results of this trial suggest that 5-FU, LV, and CDDP is an active, safe, and well-tolerated combination regimen in patients with advanced colorectal cancer.

Adenocarcinoma↗
PubMed1991

Comparative analysis of cancer-associated antigen CA-195, CA 19-9 and carcinoembryonic antigen in diagnosis, follow-up and monitoring of response to chemotherapy in patients with gastrointestinal cancer.

To establish further the clinical significance of the CA-195 tandem immunoradiometric assay in gastro-intestinal malignancies, the sera of a total of 222 subjects have been analysed and compared with assays of the "classical gastrointestinal tumour markers", CA19-9 and carcinoembryonic antigen (CEA). CA-195 elevations above normal (greater than 10 U/ml) were noted in 51/72 (70.8%) colorectal, 15/15 (100%) pancreatic, and in 6/12 (50%) gastric cancer patients. Whereas CA19-9 was increased (greater than 37 U/ml) in 65%, 93%, and 42% of cases, only 54% colorectal, 45% pancreatic, and 42% gastric cancer patients had pathologically elevated serum CEA levels (greater than 5 ng/ml). No abnormal increase of both CA-195 and CA19-9 was found in healthy volunteers, whereas 3/20 (smoking) individuals had CEA levels slightly above normal. With a 29% false-positive rate noted among 103 patients with benign gastrointestinal disorders, the specificity of CA-195 was superior to that of CA19-9 (58%) and comparable with that of CEA (31%). A significant correlation between CA-195 levels and the clinical/pathological stage of disease was noted in colorectal (P less than 0.01) and pancreatic cancer patients (P less than 0.007). Preliminary results of serial measurements of CA-195 in colorectal cancer suggest that this new marker protein, which has no cross-reactivity with CEA, may be useful as a non-invasive test for postoperative surveillance of patients to detect disease recurrence, and serve to complement (though certainly not replace) standard clinical measurements of response to chemotherapy.

Antigens, Tumor-Associated, Carbohydrate↗
PubMed1991

Phase II study of amonafide in advanced breast cancer.

Twenty-eight patients with advanced breast cancer refractory to prior hormone and/or first-line chemotherapy (with or without anthracycline drugs) were treated with the investigational agent amonafide at a dose of 800 mg/m2 intravenously over 3 hours repeated every 4 weeks. Five objective tumour responses of 5.0 months' median duration were observed in the 20 patients without previous anthracycline exposure, including 1 CR. Leukopenia was the dose-limiting toxicity; though it was generally modest with the 800 mg/m2 amonafide starting dose, an initial dose reduction should be considered in patients with prior radiotherapy and/or bone marrow involvement. Other adverse reactions included nausea/vomiting (53%), phlebitis/erythema along the vein injected (7%), and mild neurotoxic symptoms during the drug administration such as headache, tinnitus, and diaphoresis (21%). Amonafide is an active compound for the treatment of patients with advanced breast cancer and should be considered for further evaluation and incorporation in combination chemotherapy.

Adenine↗
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↗