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  • 1
    Electronic Resource
    Electronic Resource
    Springer
    Journal of molecular medicine 59 (1981), S. 1177-1188 
    ISSN: 1432-1440
    Keywords: Etoposide ; Mechanisms of action ; Pharmacoclinetics ; Toxicity ; Clinical activity ; Cancer ; Etoposid ; Wirkungsmechanismus ; Pharmakokinetik ; Toxizität ; Klinische Aktivität ; Krebs
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung Etoposid ist ein halbsynthetisches Podophyllotoxinderivat mit einem breiten zytostatischen Wirkungsspektrum und relativ günstigem therapeutischen Index. Tierexperimentell zeigt diese Substanz einen Synergismus mitCis-Platin, Cyclophosphamid, BCNU und Cytosinarabinosid. Die Wirkmechanismen sind Hemmung des Nukleosidtransports in die Zelle, Störung der DNA- und RNA-Synthese, Einzelstrangbrüche, Störung der Proteinsynthese und Hemmung mikrotubulärer Proteine. In niedriger Konzentration wirkt Etoposid zellzyklusphasenspezifisch mit Akkumulation in der G2-Phase, in höherer Konzentration auch phasenunspezifisch. Am geeignetsten unter dem Aspekt von Wirkung und Toxizität ist die intravenöse oder orale Applikation in fraktionierten Dosen von 80–120 mg/m2 an 3–5 aufeinanderfolgenden Tagen und Wiederholung nach 21 [14–28] Tagen. Neben der dosislimitierenden Knochenmarkstoxizität sind weitere Nebenwirkungen Übelkeit, Erbrechen, Fieber, Kopfschmerz, Hypotension, Phlebitis, Mukositis, Neuropathie, Kardiotoxizität, Alopezie. Etoposid gehört zu den wirksamsten Substanzen beim kleinzelligen Bronchuskarzinom mit einer Ansprechrate von 37% (10% CR) und hat eine hohe Aktivität beim NHL (36%), Hodenkarzinom (37%), Chorion Karzinom der Frau (35%), beim Neuroblastom (29%) und bei der AMML (35%). Die Aktivität von Etoposid in Kombination mit anderen aktiven Substanzen bei diesen Tumoren wird in zur Zeit laufenden Studien untersucht; beim kleinzelligen Bronchuskarzinom sowie beim testikulären Karzinom und Non-Hodgkin-Lymphom wird Etoposid in Zukunft zu den Substanzen der ersten Wahl gehören können.
    Notes: Summary Etoposide is a semisynthetic podophyllotoxin derivative with a broad spectrum of antitumor activity and a relatively high therapeutic index. The synergism in animal withcis-platinum, cyclophosphamide, BCNU, and cytosinarabinoside is interesting for combination regimen. Mechanisms of action are inhibition of nucleoside transfer and of DNA and RNA synthesis, single stranded breaks, inhibition of protein synthesis and of microtubular assembly. While in lower concentrations etoposide is acting cell-cycle-dependent with accumulation of cells in the G2-phase it has, in high concentrations, also a cellcycle-phase-unspecific lethal effect. Most suitable is the oral and i.v. application of etoposide in fractionated doses of 80–120 mg/m2 on 3–5 consecutive days and repetition after 21 [14–28] days. Side effects are dose-limiting bone marrow toxicity, nausea, vomiting, fever, hypotension, phlebitis, mucositis, neuropathy, cardiotoxicity, alopecia. Etoposide is one of the most active single agents in small-cell bronchus carcinoma with a remission rate of 37% (10% CR), and is very active in NHL (36%), testicular carcinoma (37%), AMML (35%), choriocarcinoma (35%), and neuroblastoma (29%). The role of etoposide in combination with other active drugs in these tumors is currently investigated in bronchus and testicular carcinoma and NHL, where etoposide will belong to the drugs of the first choice in the future.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-1440
    Keywords: Small cell bronchogenic carcinoma ; Induction therapy ; Maintenance ; Remission rate ; Survival ; Kleinzelliges Bronchialkarzinom ; Induktionsbehandlung ; Erhaltungstherapie ; Remissionsraten ; Überlebenszeiten
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung Seit Juli 1978 wurden 103 Patienten mit inoperablem kleinzelligem Bronchialkarzinom mit der Zytostatikakombination Adriamycin, Cyclophosphamid und Vincristin (ACO) behandelt. Im Stadium „limited disease“ (n=64) erfolgte während des zweiten Chemotherapiekurses eine prophylaktische Schädelbestrahlung, nach dem vierten eine konsolidierende thorakale Bestrahlung. Nach Erreichen einer kompletten Remission erhielten die Patienten prospektiv randomisiert Etoposid oder keine weitere spezifische Therapie. Ein objektives Ansprechen konnte bei 88/100 auswertbaren Patienten erzielt werden. Im Stadium „limited disease“ fanden sich 72%, im Stadium „extensive disease“ nur 33% komplette Remissionen. Im Stadium „limited disease“ betrug die hochgerechnete mediane Überlebenszeit 15,8, im Stadium „extensive disease“ 9,3 Monate (p〈0.005). Es leben noch 29 Patienten, 4 rezidivfrei länger als 24 Monate. Patienten mit kompletter Remission hatten eine statistisch signifikant (p〈0.001) längere Überlebenszeit als Patienten mit geringerem Ansprechen. Regelmäßig traten gastrointestinale und hämatologische Nebenwirkungen auf, drei Patienten starben während der Induktionsphase an Infektionen. Die kurzzeitige Induktionsbehandlung verbesserte jedoch den Krankheitsverlauf subjektiv und objektiv. Bisher ist kein positiver Effekt der zyklischen Etoposid-Gabe nach ACO festzustellen.
    Notes: Summary Since July 1978 one hundred and three consecutive patients with unresectable small cell bronchogenic carcinoma were treated with a combination of doxorubicin, cyclophosphamide and vincristine (ACO). In limited disease patients (64) the second chemotherapy course was followed by prophylactic cranial irradiation, the fourth by irradiation towards primary disease sites. Complete responders were randomised to either receive etoposide or no further maintenance therapy. Objective responses were reached in 88/100 evaluable patients, with 72% of complete remissions in limited-stage disease and 33% in extensive disease, respectively. The actuarial median survival time for limited disease patients was 15.8 months compared to 9.3 months in extensive disease (p〈0.005). 29 of the 100 patients remain still alive, 4 for more than 24 months without disease recurrence. The survival advantage of patients reaching complete remissions relative to those who did not is highly significant (p〈0.001). Acute gastrointestinal and hematological side effects were common, with possibly three drug-related deaths from infections during transient granulocytopenia (mean nadir: 600–900 cells/mm3). The present induction regimen using only four courses of chemotherapy produces high complete remission rates on roentgenography and bronchoscopy and improved survival in the majority of patients. Thus far any effectiveness of etoposide-maintenance therapy following ACO could not be substantiated.
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Springer
    Journal of molecular medicine 61 (1983), S. 923-927 
    ISSN: 1432-1440
    Keywords: ACE-activity ; Inoperable bronchogenic carcinoma ; Combination chemotherapy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary In 43 patients with inoperable bronchogenic carcinoma — 32 small cell and 11 squamous or large cell — Angiotensin-Converting-Enzyme (ACE) activity in serum was determined before and every 3–5 weeks during cytotoxic chemotherapy. ACE-activity prior to therapy was 10.7 U ± 1.17 SE as compared to the normal values 20.4 U ± 1.8 SE which was statistically significant (p〈0.01). There was no significant difference between the basal values of patients with small cell and not small cell-carcinoma of the lung. Only for patients with small cell-carcinoma of the lung a significant rise in ACE-activity could be obtained. Mean values of these patients reached normal levels in case they had complete remission, which was achieved in the limited disease group in 82% of patients. The present data suggest, that ACE-activities in serum correspond well to the clinical course in patients with small cell carcinoma of the lung. The decision on the individual mode of therapy may thus become more substantiated by serial determinations of ACE in the course of treatment.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1432-1440
    Keywords: Interferon alpha-2b ; Nephrotoxicity ; Urinary enzymes
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The nephrotoxic potential of alpha-interferon (IFN alpha-2b) was analysed in 21 patients with chronic myeloid leukemia. As particularly sensitive parameters in the detection of subclinical renal injury we measured the excretion of the following urinary enzymes: lactate dehydrogenase (LDH), gamma-glutamyltransferase (GGT), leucine arylaminidase (LAP), β-galactosidase (GAL) and N-acetyl-beta-glucosaminidase (NAG). Additionally, protein excretion and urinary sediment were analysed. In 18 of 21 patients a significant increase in the excretion of LDH, LAP, GGT and NAG was found, in 6 patients there was an additional rise in the output of GAL. Eleven patients developed proteinuria up to 2 g/l, one patient excreted up to 9 g/l. Enzymuria and protein excretion decreased in all patients after reduction of the IFN alpha-2b dosage and disappeared in two patients following cessation of therapy. The high incidence of nephrotoxic events in patients with CML during IFN alpha-2b therapy might be mostly due to immunological or substance-specific effects.
    Type of Medium: Electronic Resource
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  • 5
    Electronic Resource
    Electronic Resource
    Springer
    Journal of molecular medicine 65 (1987), S. 706-712 
    ISSN: 1432-1440
    Keywords: Hairy-cell leukemia ; Interferon gamma ; Interferon alpha-2b
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung 6 Patienten mit einer Haarzellenleukämie wurden 3–35 Monate nach Splenektomie mit IFN-γ (4 × 106 E/m2/2. Tag sc) behandelt. Während einer Therapiedauer von 9–35 Wochen konnte bei keinem Patienten eine signifikante klinische oder hämatologische Befundbesserung erzielt werden. Nach einem therapiefreien Intervall von 0–13 Wochen erhielten alle Patienten IFN-α-2b (zunächst 4 × 106 E/m2/2. Tag, Erhaltungstherapie 1 × 106 E/2. Tag). Zum Zeitpunkt der Beendigung der jeweiligen IFN-α-2b-Gabe war bei 5 von 6 Patienten (1 Patient mit postthrombotischem Syndrom verstarb an einer Lungenembolie) eine deutliche Befundbesserung eingetreten. Nach einer Beobachtungszeit von jetzt 9–14 Monaten konnten 1 CR, 3 PR und 1 MR induziert werden. Die Nebenwirkungen beider Interferon-Präparationen unterschieden sich nicht signifikant.
    Notes: Summary Six patients with hairy-cell leukemia were treated with gamma-(IFN-γ) and alpha-(IFN-α-2b) interferon; 3–35 months following splenectomy, treatment was started with 4 × 106 U/m2 IFN-γ sc (iv) every second day for 9–35 weeks. Although the white blood cell counts decreased during therapy from 4.1–49 × 109/1 to 1.5–43 × 109/1, no hematological or clinical improvement was obtained. Subsequently (interval 0–13 weeks), IFN-α-2b was given at an initial dose of 4 × 106 U/m2 sc every second day to all patients. After a treatment period corresponding to that of IFN-γ administration, a significant hematological improvement was observed in five patients (one early death due to pulmonary embolism). At the last follow-up (9–14 months after start of treatment; maintenance therapy, 1 × 106 U every second day), these patients exhibited normal peripheral blood cell counts, and in bone marrow biopsy specimens a marked decrease of hairy cells was seen (1 CR, 3 PR, 1 MR). Adverse reactions including fever, headache, nausea, dryness of the mouth, myalgia, and fatigue did not significantly differ between the two interferon preparations. Whereas IFN-γ is unlikely to have any significant impact on the course of hairy cell leukemia, IFN-α-2b does result in improvement of hematological values and well-being in almost all patients.
    Type of Medium: Electronic Resource
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  • 6
    Electronic Resource
    Electronic Resource
    Springer
    Journal of molecular medicine 58 (1980), S. 875-880 
    ISSN: 1432-1440
    Keywords: Multiple myeloma ; Viscosity ; Water of serum ; Hyponatremia ; Maligne Paraproteinämie ; Viskosität ; Serumwassergehalt ; Hyponatriämie
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung In der vorliegenden Arbeit wurden Häufigkeit und Ursachen von Elektrolytstörungen bei malignen Paraproteinämien untersucht. 7 von 15 Patienten wiesen z.T. extreme (bis 93 mmol/l), jedoch immer symptomlose Hyponatriämien auf. Gegenüber einer Kontrollgruppe war die Serumviskosität signifikant erhöht. Zwischen der Serumnatriumkonzentration und der Viskosität bestand eine hochsignifikante negative Korrelation. Die Kontrolle der Serumnatriumwerte durch viskositätsunabhängige Meßsysteme erwies, daß die beobachteten Hyponatriämien durch Verdünnungsfehler in dem von uns routinemäßig verwandten viskositätsabhängigen Analyseverfahren bedingt waren. Die Erniedrigung des Serumwasseranteils trug in geringem Maße ebenfalls zur Entstehung einer Hyponatriämie bei. Bei der durch Paraproteine hervorgerufenen Serumnatriumverminderung handelt es sich nach unseren Befunden um eine vorgetäuschte und nicht behandlungsbedürftige Hyponatriämie.
    Notes: Summary In the present study frequency and mechanisms of alterations in serum electrolytes in multiple myeloma were investigated. Asymptomatic hyponatremia (up to 93 mmol/l) was present in 7 of 15 patients. Water of serum was significantly lower, viscosity of serum significantly raised as compared to healthy controls. A highly significant negative correlation between sodium concentration and viscosity was found. By measuring serum sodium concentration with viscosity independent dilution systems it could be proved that in each case the observed hyponatremia was caused by flaws in our routinely used viscosity dependent dilution method. The decrease in water of serum contributed only little to the development of hyponatremia. It is concluded that the decrease in serum sodium concentration in multiple myeloma is nothing else than a feigned hyponatremia which needs no therapy.
    Type of Medium: Electronic Resource
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  • 7
    ISSN: 1432-1440
    Keywords: Testicular neoplasms ; Stage II ; Combination chemotherapy ; Radiotherapy ; Lymph node dissection ; Testikuläre Tumoren ; Stadium II ; Kombinierte Chemotherapie ; Radiotherapie ; Lymphknoten-Exstirpation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung Seit 1975 wurden 140 Patienten mit retroperitoneal-metastasierten nicht-seminomatösen Hodentumoren nach Orchiektomie und retroperitonealer Lymphadenektomie sequentiell alternierend mit den Zytostatika-Kombinationen Velbe/Bleomycin und Adriamycin/Cisplatin plus/minus Radiotherapie behandelt. Davon erhielten 68 Patienten nach totaler retroperitonealer Lymphadenektomie mit postoperativ normalisierten Tumormarkern (Stadium IIA) 6 Chemotherapie-Kurse, woran sich bei 35 Patienten eine Strahlentherapie anschloß. Vierzig Patienten wurden nach subtotaler retroperitonealer Lymphadenektomie oder bei postoperativ erhöhten Tumormarkern (Stadium IIB) und 32 Patienten nach palliativer Lymphadenektomie (Stadium IIC) mit mindestens 12 Chemotherapie-Kursen und fakultativer intermittierender Radiotherapie und/oder Relaparotomie behandelt. Der Vergleich der Behandlungsergebnisse bei den Stadien IIA und IIB ergab unabhängig von der zusätzlichen Radiotherapie nach der „Life-table“-Methode Vier-Jahres-Überlebensraten zwischen 80 und 100%. Diese günstigen Resultate sind mit den Ergebnissen bei 34 nicht adjuvant behandelten Patienten ohne histologisch nachweisbare retroperitoneale Metastasierung (Stadium I) vergleichbar. Ausdruck einer statistisch signifikant schlechteren Prognose bei fortgeschrittener retroperitonealer Metastasierung ist eine Vier-Jahres-Überlebensrate von 12% bei den Patienten im Stadium IIC.
    Notes: Summary Following orchiectomy and retroperitoneal lymph node dissection (RND) 140 patients with stage II non-seminomatous testicular cancer were treated by sequential combination chemotherapy consisting of vinblastine/bleomycin and adriamycin/cis-dichlorodiammineplatinum(II) (DDP), plus/minus radiotherapy. 68 stage IIA-patients (complete RND and normal tumor-markers thereafter) received 6 courses of chemotherapy, followed by radiotherapy in 35 patients. 40 stage IIB-patients (minor residual disease after RND or elevated tumor-markers after RND) and 32 stage IIC-patients (advanced residual disease after RND) were treated by at least 12 chemotherapy courses and optional intermittent radiotherapy and/or relaparotomy. In stage IIA and IIB disease the actuarial 4-year survival rates were between 80 and 100%. These favourable results were not significantly influenced by additional radiotherapy and corresponded to the survival rates for 34 stage I-patients. For stage IIC-patients the prognosis was significantly worse with a 12% 4-year survival rate.
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  • 8
    ISSN: 1432-1440
    Keywords: Small-cell lung cancer ; Primary resistance ; Relapse ; Vindesine ; Cisplatin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Thirty-eight pretreated patients with primarily resistant [6] or relapsed [32] small-cell lung cancer were treated with a combination of vindesine (3–4 mg/m2) and cisplatin (60–100 mg/m2). Eight patients responded to this therapy with three (8%) complete and five (13%) partial remissions. Minor responses were noted in 12 (32%) additional patients. Chemotherapeutic response was rare in regions of prior irradiation. In the complete remission group survival from start of vindesine/cisplatin therapy lasted 61, 48 and 38 weeks, respectively. In the “less-than-complete-remission” group median survival was 12 weeks. Nausea and vomiting were the prominent side-effects, while only mild to moderate myelosuppression was noticed in most cases. The vindesine/cisplatin combination showed significant activity in heavily pretreated small-cell lung carcinoma. However, the remission rates remain low in this unfavourable condition, which might be due to pronounced chemotherapeutic resistance in previously irradiated areas.
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  • 9
    ISSN: 1432-1440
    Keywords: Antiemetic therapy ; Alizapride ; Cisplatin ; Nabilone
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Twenty nonseminomatous testicular cancer patients not pretreated with emetogenic chemotherapy were included in a crossover study of antiemetic therapy. Patients were randomly assigned to receive either nabilone (2×2 mg/day) or alizapride (3×150 mg/day) prior to beginning lowdose cisplatin chemotherapy. Patients on nabilone had significantly fewer episodes of emesis than those on alizapride (medians, 1.1 vs 2.9;p〈0.01). Nabilone was superior to alizapride in giving complete relief from nausea (medians, 65% vs 30%;p〈0.01), and was more effective in shortening the duration of nausea (medians, 1.3 h vs 5.1 h;p〈0.01); however, it caused more adverse effects. It is concluded that nabilone has greater antiemetic activity than alizapride in young patients receiving low-dose cisplatin chemotherapy. Nabilone dosage should be reduced to decrease the incidence and degree of adverse reactions while leaving the definite antiemetic activity unchanged.
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  • 10
    ISSN: 1365-2559
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: In addition to predominant granulocytic proliferation, bone marrow morphology in Philadelphia chromosome positive (Ph1+) CML is characterized by atypical dwarf or microforms of megakaryocytes. However, following therapy with interferon-α2b (IFN), these micromegakaryocytes occur less frequently. The purpose of this study was to elucidate whether the reappearance of normal megakaryocytes may be associated also with a reduction of the bcr/abl-positive cell clone.〈section xml:id="abs1-2"〉〈title type="main"〉Methods and results:Fluorescence in-situ hybridization (FISH) technique in combination with immunomorphometry (CD61) was performed on trephine biopsies. A total of 311 CD61-positive megakaryocytes, including precursors and atypical microforms, were evaluated in pre-treatment specimens derived from 11 patients with Ph1+ CML. A specific fusion site marking the bcr/abl translocation was found in 87% of megakaryocytes which showed a size of 169 ± 35 μm2. In untreated patients, atypical microforms (size 200 μm2) were observed in 66% of the total megakaryocytic population. Following IFN therapy 369 megakaryocytes could be analysed in sequential examinations and were found to display a significant decrease (63%) in positive fusion signals. In addition there was also a significant enhancement in average size (252 ± 66 μm2) reflecting a reduction in the number of micromegakaryocytes (43%). These findings were particularly conspicuous in three patients with a major to complete cytogenetic remission.〈section xml:id="abs1-3"〉〈title type="main"〉Conclusions:A normalization of megakaryocyte size following IFN therapy in CML is significantly associated with a loss of the bcr/abl translocation site and therefore indicates a (partial) recovery of normal haematopoiesis.
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