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  • 1
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Annals of the New York Academy of Sciences 680 (1993), S. 0 
    ISSN: 1749-6632
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Natural Sciences in General
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    World journal of surgery 12 (1988), S. 345-348 
    ISSN: 1432-2323
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Résumé Pour prévenir la récidive des sarcomes, la perfusion isolée a été employée après résection de 15 sarcomes des membres. Elle a concerné 6 liposarcomes, 4 sarcomes synoviaux, 2 fibrohistiocytomes malins, 1 sarcome de Kaposi, et 1 ostéosarcome (le seul cas de sarcome osseux). Le protocole thérapeutique a compris 2 étapes: (a) ablation de la tumeur avec une marge de sécurité suffisante passant à l' exterieur de la capsule tumorale, (b) puis après 3 à 8 semaines circulation extracorporelle pendant une heure de melphalan associé ou non à de 1 'actinomycine D sous hyperthermie modérée à 39–41°C. La médiane du temps de suivi a été de 30 mois. Quatre sur huit des récidives sarcomateuses ont récidivé à nouveau et ont vu se développer des métastases. Par contre, aucun malade qui n 'avait pas été traité préalablement n'a récidivé et un a présenté une dissémination tumorale sous la forme d'un liposarcome à foyers multiples. Onze sont encore en vie, la durée de la survie étant comprise entre 8 et 103 mois. Les auteurs concluent de ces faits que la circulation extracorporelle avec du melphalan associé ou non à de l'actinomycine D peut être considérée comme un traitement complémentaire du traitement chirurgical.
    Abstract: Resumen Con miras a la prevención de recurrencias, se aplicó perfusión aislada en 15 pacientes después de resección de sarcomas de las extremidades. El grupo incluyó 6 liposarcomas, 4 sinoviosarcomas, 2 fibrohistiocitomas malignos, 1 mesenquimoma maligno, 1 Kaposi, y 1 osteosarcoma (el único sarcoma óseo). Ocho sarcomas representaron recurrencia después de cirugía limitada y/o radioterapia. El programa terapéutico fue conducido en 2 etapas: (a) remoción del tumor con márgenes de seguridad por lo menos por fuera de la cápsula tumoral, seguida 3–8 semanas después de (b) perfusión aislada con melfalán con o sin actinomicina D bajo hipertermia moderada a 39–41°C por 1 hora. El promedio de seguimiento ha sido de 30 meses. Cuatro de los 8 sarcomas recurrentes presentaron la recurrencia de nuevo y desarrollaron metástasis distales. En contraste, ninguno de los pacientes que no habían recibido tratamiento previo presentó recurrencia y en uno se diseminó en la forma de un liposarcoma multicéntrico. Once permanecen vivos con supervivencia entre 8 y 103 meses. Nuestra conclusión es que la perfusión aislada con melfalán con o sin actinomicina D puede ser considerada como una terapia adyuvante de la cirugía.
    Notes: Abstract In order to prevent recurrence, isolation perfusion was applied in 15 patients after resection of sarcomas of the limbs. There were 6 liposarcomas, 4 synoviosarcomas, 2 malignant fibrohistiocytomas, 1 malignant mesenchynoma, 1 Kaposi, and 1 osteosarcoma (the only bone sarcoma). Eight sarcomas were recurrent after narrow surgery and/or radiotherapy. The treatment schedule was conducted in 2 steps: (a) removal of the tumor with safety margins at least outside the tumor capsule, followed 3–8 weeks later by (b) isolation perfusion with melphalan with or without actinomycin D under moderate hyperthermia at 39–41°C for 1 hour. Median follow-up time has been 30 months. Four of the 8 recurrent sarcomas recurred again and developed distal metastases. In contrast, none of the previously untreated patients recurred and 1 disseminated in the form of multicentric liposarcoma. Eleven are still alive with survival ranging from 8 to 103 months. It is concluded that isolation perfusion with melphalan with or without actinomycin D may be considered as an adjunct to surgery.
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Springer
    World journal of surgery 12 (1988), S. 340-344 
    ISSN: 1432-2323
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Résumé Les auteurs ont étudié 23 cas de désarticulations proximales pour sarcome en ayant pour but d'apprécier la valeur de l'intervention, la désarticulation étant précédée de radiothérapie et de chimiothérapie. Les critères retenus furent: l'existence de récidives, la survie et la qualité de la vie. La série a concerné 14 sarcomes des parties molles, 9 sarcomes des os. Dans 11 cas il s'agissait d'une tumeur primitive, dans 13 cas de récidives tumorales. Sur ce groupe de malades, 18 avaient été traités par une intervention limitée, 11 par radiothérapie, et 10 par chimiothérapie. En ce qui concerne le membre supérieur, 6 ont été traités par désarticulations inter-scapulo-thoraciques, et 3 par une résection inter-scapulo-thoracique selon la technique de Tikhoff-Linberg. En ce qui concerne le membre inférieur, 8 malades ont été soumis à une désarticulation interilio-abdominale, 3 à une désarticulation ilio-coxo-fémorale, et 1 à une hémipelvectomie interne selon la technique de Eilber. La moyenne de durée de vie normale a été de 34 mois et la moyenne de la durée de la survie de 38.5 mois. Trois (15%) des 20 malades qui ont été revus ont présenté une récidive locale mais la majorité d'entre eux ont pu bénéficier d'une réintervention. La qualité de la vie a été excellente en général bien que 8 opérés seulement aient accepté le port d'une prothèse. L'index de Karnofsky a varié de 60 à 100%. Aucune différence significative n'a été observée que le malade ait été soumis ou non à la radiothérapie et/ou à la chimiothérapie.
    Abstract: Resumen Los autores han revisado 23 pacientes con desarticulaciónes proximales con el propósito de determinar el valor terapéutico en el sarcoma, habida consideración a radioterapia y quimioterapia previas. Los siguientes criterios fueron específicamente analizados: recurrencia, supervivencia, y calidad de la vida. La serie incluyó 14 sarcomas de tejidos blandos, y 9 sarcomas óseos. En 11 casos el tumor era primario y aparecía tratado por primera vez, y en 12 casos el tumor era recurrente. Diez y ocho pacientes habían sido previamente tratados con cirugía no radical, 11 con radioterapia, y 10 con quimioterapia. En cuanto a los tumores del miembro superior, 6 pacientes fueron sometidos a desarticulación interescápulotorácica, y 3 a resección interescapulotorácica según Tikhoff-Linberg. En cuanto a los tumores del miembro inferior, 8 pacientes fueron sometidos a desarticulación interilioabdominal, 3 a desarticulación coxofemoral, y 1 a hemipelvectomía interna según Eilber. El promedio de estado libre de enfermedad ha sido 34 meses, y el promedio de supervivencia, 38.5 meses. Tres (15%) de 20 pacientes valorables presentaron recurrencia aunque la mayoría de ellos se benefició con una segunda operación. En general, la calidad de la vida ha sido excelente a pesar de que solamente 8 pacientes aceptaron usar prótesis. El índice de Karnofsky osciló entre 60 y 100%. No se observó diferencia entre los pacientes que habían recibido radioterapia y/o quimioterapia y los que no la recibieron.
    Notes: Abstract The authors have reviewed 23 patients with proximal disarticulations with the aim of assessing the therapeutic value in sarcoma, taking into account previous radio- and chemotherapy. The following criteria were especially examined: recurrences, survival, and quality of life. There were 14 soft tissue sarcomas, and 9 bone sarcomas. In 11 cases, the tumor was primary and treated for the first time while, in 12 cases, it was recurrent. Eighteen patients had been previously treated by nonradical surgery, 11 by radiotherapy, and 10 by chemotherapy. For upper limb tumors, 6 patients underwent an interscapulothoracic disarticulation, and 3 an interscapulothoracic resection according to Tikhoff-Linberg. For lower limb tumors, 8 patients were submitted to interilioabdominal disarticulation, 3 to coxofemoral disarticulation, and 1 to internal hemipelvectomy according to Eilber. The mean disease-free interval has been 34 months, and the mean survival, 38.5 months. Three (15%) of 20 evaluable patients recurred locally, although most of them benefited from second surgery. Quality of life has been excellent, in general, despite the fact that only 8 patients accepted to wear a prosthesis. The Karnofsky index ranged from 60 to 100%. No significant difference was seen, whether or not previous radio- and/or chemotherapy had been administered.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1569-8041
    Keywords: melanoma ; pharmacodynamics ; pharmacokinetics ; temozolomide
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background: The DNA repair protein O6-alkylguanine-DNA alkyl transferase (AT) mediates resistance to chloroethylnitrosoureas. Agents depleting AT such as DTIC and its new analogue temozolomide (TMZ) can reverse resistance to chloroethylnitrosoureas. We report the results of a dose finding study of TMZ in association with fotemustine. Patients and methods: Twenty-four patients with metastatic melanoma or recurrent glioma were treated with escalating dose of oral or intravenous TMZ ranging from 300 to 700 mg/m2, divided over two days. Fotemustine 100 mg/m2 was given intravenously on day 2, 4 hours after TMZ. AT depletion was measured in peripheral blood mononuclear cells (PBMCs) and in selected cases in melanoma metastases and was compared to TMZ pharmacokinetics. Results: The maximum tolerated dose (MTD) of TMZ was 400 mg/m2 (200 mg/m2/d) when associated with fotemustine the 2nd day with myelosuppression as dose limiting toxicity. The decrease of AT level in PBMCs was progressive and reached 34% of pretreatment values on day 2. There was however wide interindividual variability. AT reduction was neither dose nor route dependent and did not appear to be related to TMZ systemic exposure (AUC). In the same patients, AT depletion in tumour did not correlate with the decrease of AT observed in PBMCs. Conclusions: PBMCs may not be used as a surrogate of tumour for AT depletion. Further study should concentrate on the pharmacokinetic pharmacodynamic relationship in tumour to provide the basis for individually tailored therapy.
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 0730-2312
    Keywords: melanoma ; TNFα ; isolation perfusion ; melphalan ; interferon-γ ; Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: Recombinant tumor necrosis factor-alpha (rTNFα) has potent antitumor activity in experimental studies on human tumor xenografts. However, in humans, the administration of rTNFα is hampered by severe systemic side-effects. The maximum tolerated dose range from 350 to 500 mg/m2, which is at least 10-fold less than the efficient dose in animals. Isolation perfusion of the limbs (ILP) allows the delivery of high dose rTNFα in a closed system with acceptable side-effects. A protocol with a triple-drug regimen was based on the reported synergism of rTNFα with chemotherapy, with interferon-y, and with hydperthermia. In melanoma-in-transit metastases (stage IIIA or AB) we obtained a 91% complete response, compared with 52% after ILP with melphalan alone. Release of nanograms levels of TNFα in the systemic circulation was evident but control of this leakage and appropriate intensive care resulted in acceptable toxicity. Angiographic, immunohistological, and immunological studies suggest that the efficacy of this prtocol is due to a dual targeting: rTNFα activates and electively lyses the tumor endothelial cells while melphalan is mainly cytoxic to the tumor cells. ILP with rTNFα appears to be a useful model for studying the biochemotherapy of cancer in man.
    Additional Material: 2 Ill.
    Type of Medium: Electronic Resource
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