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  • 1
    Electronic Resource
    Electronic Resource
    Amsterdam : Elsevier
    Journal of Steroid Biochemistry 28 (1987), S. 181 
    ISSN: 0022-4731
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Biology , Chemistry and Pharmacology
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 0022-4731
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Biology , Chemistry and Pharmacology
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Amsterdam : Elsevier
    Journal of Steroid Biochemistry 28 (1987), S. 180 
    ISSN: 0022-4731
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Biology , Chemistry and Pharmacology
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1569-8041
    Keywords: metastatic breast cancer ; paclitaxel ; weekly 24-hour 5-FU/leucovorin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Purpose: To evaluate the antitumor activity in terms of response rate (RR), time to progression (TTP) and survival of paclitaxel in combination with weekly 24-hour infusional 5-fluorouracil (5-FU)/leucovorin in pretreated metastatic breast cancer (MBC). Patients and methods: Fifty-four patients with bidimensionally measureable disease were included during phase II. Thirty-two had anthracycline resistant disease. Treatment consisted of 5-FU (24-hour i.v. infusion) 2.0 g/m2, leucovorin (two-hour i.v. infusion prior to 5-FU) 500 mg/m2, weekly for six weeks (day 1, 8, 15, 22, 29, 36) and paclitaxel (three-hour i.v. infusion) 175 mg/m2 was administered additionally on days 1 and 22, q 50 days. Results: We observed complete remissions in 4% of patients (2 of 54), partial remissions in 55% (30 of 54), stable disease in 37% (20 of 54) and progressive disease in 4% (2 of 54). The overall RR was 59% (95% CI 48%–72%). The RR in 32 patients with anthracycline resistant disease was 59% (19 of 32). The median duration of response was 12 months (3–22), median TTP eight months (2–22) and median survival time 15 months (2–28). Neutropenia was common, but of CTC grade 2 or 3 in most patients. Nonhematologic toxicities mostly consisted of CTC grade 1 and 2 myalgia, diarrhea, mucosits, nausea and vomiting. Conclusions: Paclitaxel combined with weekly 24-hour infusional 5-FU/leucovorin is well tolerated in the second line treatment of MBC. High efficacy was documented even in the treatment of anthracycline resistant disease, which warrants further evaluation.
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1569-8041
    Keywords: biochemical modulation ; 5-fluorouracil ; methotrexate ; pancreatic cancer ; phosphonacetyl-L-aspartate
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Purpose: To evaluate the effect of biochemical modulation by PALA and methotrexate on the therapeutic activity of 5-fluorouracil (5-FU) in patients with advanced pancreatic adenocarcinoma. Patients and methods: The treatment protocol consisted of phosphonacetyl-L-aspartate (PALA) 250 mg/m2 i.v. 15-minute infusion followed by methotrexate 200 mg/m2 i.v. 30-minute infusion on day 1 and 5-FU 600 mg/m2 i.v. push on day 2. Folinic acid was given at 15 mg/m2 p.o. every six hours for eight doses, starting 24 hours after methotrexate infusion. Cycles were repeated every two weeks. Results: Thirty patients with advanced chemotherapy-naive pancreatic cancer were included; 26 had measurable disease. Median age 56 years (27–72); median PS 1 (0–2). One PR (3.9%) was achieved; nine patients had stable disease. Median time to progression was 91 days. Median survival was 177 days and one year survival was 13.3% (4 of 30 patients). Treatment was well tolerated; diarrhea WHO grade 2 or 3 occurred in six patients; stomatitis WHO grade 2 and 3 in nine patients. Conclusions: Modulation of 5-FU by PALA and MTX given in this dose and schedule appears to be ineffective in patients with advanced pancreatic adenocarcinoma.
    Type of Medium: Electronic Resource
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  • 6
    ISSN: 1432-0843
    Keywords: Key words Anthracyclines ; Epirubicin ; Interferon ; Hepatocellular carcinoma
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Single-agent activity for anthracyclines reflected by response rates of 10%–30% has been reported in patients with advanced hepatocellular carcinoma (HCC). Preclinical data indicate that α-interferon could enhance the cytotoxic activity of the anthracycline Adriamycin or its analog epirubicin. In a phase I/II study, 31 patients with biopsy-proven inoperable HCC were treated with interferon-α2b given s.c. at a dose of 3×106 units/m2 per day for 5 days per week plus weekly epirubicin given at 25 mg/m2 as an i.v. bolus. The protocol called for 4 consecutive weeks of treatment followed by 1 week off treatment. In all, 15 patients had been previously treated; 6 patients had failed hormonal therapy (tamoxifen), 5 patients had failed prior anthracycline treatment, and 4 patients had received chemoembolization of the tumor and had subsequently progressed. A total of 30 patients were evaluable for response. In all, 1 patient (3%) achieved a partial response for 8+ months and 11 patients (35%) achieved stabilization of disease. Six patients had a fall in alpha-fetoprotein (AFP) values of 〉50% during therapy. The median survival for all patients was 9.5 months (range, 3–34+ months). The main side effects were hematological toxicity and fever, both of which were considered tolerable. As an indicator of the immunostimulatory effects of interferon, an elevation in serum markers of inflammation [C-reactive protein (CRP), β2-microglobulin] was found in 15%–20% of patients. All patients had measurable Mx protein production during therapy, but these effects were not correlated to the clinical response. The clinical response rate achieved in this trial indicates that the combination of interferon and epirubicin, at least when used on the schedule reported herein, is not superior to treatment with either agent alone for patients with advanced HCC. However, single patients achieved a prolonged progression-free interval (8–10+ months) on this therapy, and it may therefore be an option for patients who have failed prior hormonal or single-agent anthracycline therapy.
    Type of Medium: Electronic Resource
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  • 7
    Electronic Resource
    Electronic Resource
    Springer
    Der Onkologe 6 (2000), S. 443-449 
    ISSN: 1433-0415
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Der Beginn der Angiogenese stellt einen entscheidenen Schritt während des Wachstums eines Tumors und seiner lokalen Ausbreitung einschließlich seiner Fernmetastasierung dar. Nach heutigem Kenntnisstand erscheinen 3 Strategien der Angiogeneseinhibition erfolgversprechend: 1. Inhibition und/oder Neutralisation angiogener Mediatoren, 2. Inhibition der Synthese und des Umbaus der Gefäßbasalmembran und des Abbaus der extrazellulären Matrix, 3. Inhibition der Endothelzellproliferation und -migration. In verschiedenen Tiermodellen zeigten eine ganze Reihe von antiangiogenen Substanzen überzeugende Erfolge; mehrere dieser Substanzen werden zurzeit in klinischen Phase-I- und -II-Studien evaluiert. Ein neuer antiangiogener Therapieansatz besteht in der Inhibition des αvβ3-Integrins, das hauptsächlich auf proliferierenden Tumorgefäßen exprimiert wird und eine Schlüsselstellung im angiogenen Prozess einnimmt. Die Blockierung des Integrins durch den Antagonisten inhibiert die bFGF- und VEGF-stimulierte Angiogenese und induziert die Apoptose von Endothelzellen. Erste klinische Erfahrungen mit dem Integrinantagonisten und einer weiteren Reihe von Angiogeneseinhibitoren lassen vermuten, dass eine optimale antiangiogene Therapie auf einer Langzeitbehandlung in Kombination mit konventionellen Maßnahmen wie Chirurgie, Strahlenbehandlung, oder konventioneller Hormon- und Chemotherapie basieren wird.
    Type of Medium: Electronic Resource
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  • 8
    Electronic Resource
    Electronic Resource
    Springer
    Der Onkologe 5 (1999), S. 47-54 
    ISSN: 1433-0415
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Die zytostatische Chemotherapie ist etablierter Bestandteil im Behandlungskonzept des kolorektalen Karzinoms. Im metastasierten Stadium führt eine auf 5-Fluorouracil-basierende Chemotherapie zu einer signifikant längeren Überlebenszeit und zu einer deutlichen Reduktion tumorbedingter Symptome. In den letzten Jahren wurden zudem mehrere Substanzklassen, die eine relevante Aktivität beim kolorektalen Karzinom zu besitzen scheinen und damit potentiell das therapeutische Arsenal erheblich erweitern könnten, entwickelt und klinisch geprüft. Im folgenden Artikel wird ein Überblick über den derzeitgen Entwicklungsstand der wichtigsten neuen Substanzen für die Therapie des kolorektalen Karzinoms gegeben.
    Type of Medium: Electronic Resource
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  • 9
    Electronic Resource
    Electronic Resource
    Springer
    Der Onkologe 4 (1998), S. 532-540 
    ISSN: 1433-0415
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Metastasierte Keimzelltumoren des Hodens sind mit der Entwicklung cisplatinbasierter Kombinationschemotherapien heute bei 70–80% aller Patienten heilbar geworden [3, 12]. Es besteht ein genereller Konsens, daß bei allen nicht-seminomatösen Keimzelltumoren des Hodens mit abdomineller Lymphknotenmetastasierung größer 5 cm oder Metastasen in anderen Lokalisationen eine primäre Chemotherapie nach der hohen inguinalen Orchiektomie das Standardvorgehen darstellt [1]. Der therapeutische Erfolg wird dabei anhand der häufig im Serum erhöht meßbaren Tumormarker Alpha-Fetoprotein (AFP) und Beta-Humanes-Chorion- Gonadotropin (β-HCG) sowie anhand des radiologischen Verlaufs beurteilt. Bei Ansprechen auf die durchgeführte Kombinationschemotherapie und Markernormalisierung, aber residuellen Tumorherden, schließt sich in der Regel eine chirurgische Entfernung dieser Residuen an [3, 8, 9, 16].
    Type of Medium: Electronic Resource
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  • 10
    ISSN: 1432-1335
    Keywords: Testicular cancer ; GM-CSF ; Cisplatin ; Etoposide ; Ifosfamide
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary In order to develop a more dose-intensive induction regimen for the treatment of far-advanced testicular tumours, the German Cooperative Group for Testicular Tumours started a dose-escalation trial of cisplatin, etoposide and ifosfamide. At the first dose level 18 patients with advanced testicular cancer (Indiana University classification) received cisplatin 25 mg/m2, etoposide 120–150 mg/m2 and ifosfamide 1.2 g/m2 for 5 days every 3 weeks. Of these, 13 patients (72%) became tumour-free, 2 achieved a stable, marker-negative partial remission, 2 had progressive disease and 1 patient died ofClostridium sepsis. The main toxicity was myelosuppression with a white blood cell nadir of 900/μl and a thrombocyte nadir of 47000/μl. Granulocytopenic fever occurred in 43% of all cycles. At the second dose level 15 patients received cisplatin 30 mg/m2, etoposide 150 mg/m2 and ifosfamide 1.6 g/m2 five times every 3 weeks together with s.c. recombinant granulocyte/macrophage-colony-stimulating factor (GM-CSF) 10 μg/kg on days 6–15. Acute toxicity was severe with a white blood cell nadir of 300/μl and thrombocyte nadir of 11 000/μl. The duration of the thrombocytopenia increased with cycle number; 63% of all cycles were associated with granulocytopenic fever and in 83% platelet transfusions were required. One patient died from acute renal failure andAspergillus sepsis; 3 patients experienced adverse reactions to GM-CSF, requiring omission of this drugs in 2; 33% had grade 3 or 4 mucositis. At this dose level 8 patients (53%) became tumour-free, 4 patients (26%) had marker normalization with irresectable residual disease and 2 patients were treatment failures. Though acute toxicity was severe at this dose level, there was no unexpected or unmanageable organ toxicity and thus patients are now entered at dose level 3, which consists of cisplatin 30 mg/m2, etoposide 200 mg/m2 and ifosfamide 1.6 g/m2 for 5 days and GMCSF 10 μg kg−1 day−1 on days 6–15 s.c.
    Type of Medium: Electronic Resource
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