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  • 1
    Language: English
    In: Journal of Cancer Research and Clinical Oncology, 2003, Vol.129(6), pp.361-366
    Description: To determine the feasibility, time to progression, and event-free survival, twenty-two women with metastatic breast cancer received two cycles of high-dose chemotherapy (HDCT) followed by peripheral blood stem cell transplantation (PBSCT) early after first-line induction chemotherapy. The median age of the ten (45.5%) pre- and 12 (54.5%) postmenopausal women was 48 (range: 33–60) years. Sixteen patients (72.7%) had at least two or more metastatic sites involved. Protocol induction and mobilization chemotherapy including granulocyte-colony stimulating-factor (G-CSF) consisted of two cycles with adriamycin (60 mg/m 2 ) i.v. and paclitaxel (200 mg/m 2 ) i.v. After collection of at least 4×10 6 /kg bodyweight peripheral blood stem cells, the first HDCT-course of adriamycin (60 mg/m 2 ), paclitaxel (200 mg/m 2 ) cyclophosphamide (4 g/m 2 ), and thiotepa (800 mg/m 2 ) (ATCT) was given to at least stable disease (SD) patients. Six to eight weeks later, the second HDCT-ATCT was administered. Each HDCT-cycle was followed by PBSCT with a median of 3.81×10 6 /kg bodyweight CD-34 positive cells (range: 1.85–10.38). All women showed median leukocyte engraftment (〉1,000×10 9 /l) on day +9.4 (range: 7–13) and median platelet engraftment (〉20,000×10 9 /l) on day +12.3 (range: 8–15). There were no apparent differences in the clinical course and non-hematologic toxicity between the two HDCT-cycles. Of the 21 patients evaluable for response, eight (38.1%) patients achieved complete remission (CR), ten (47.6%) patients showed a partial remission (PR), two patients (9.5%) no change, and one patient (4.8%) progressive disease. After a median observation time of 36 (range 28–55) months, six (28.6%) women are alive, four (19.0%) of them in continuous CR, including two women with stable bone lesions, respectively, and 15 (71.4%) died due to progressive disease. Median time to progression (TTP) was 8 (range 4–19) months. A high initial response rate of early HDCT, including the most active drugs adriamycin and paclitaxel, can be achieved with tolerable toxicity in metastatic breast cancer. New approaches for maintaining primary tumor response achieved with efficacious high-dose chemotherapy are warranted.
    Keywords: Metastatic breast cancer ; High-dose chemotherapy ; Adriamycin ; Paclitaxel ; Autologous stem cell transplantation
    ISSN: 0171-5216
    E-ISSN: 1432-1335
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  • 2
    Language: German
    In: Medizinische Klinik, 1997, Vol.92(7), pp.410-414
    Description: Die Anwendung hämatopoetischer Wachstumsfaktoren und die Retransfusion patienteneigener, aus dem Blut gewonnener peripherer Blutstammzellen (PBSZ) hat in den letzten Jahren die Option zur Durchführung einer Hochdosischemotherapie (HDT) auch bei fortgeschrittenen soliden Tumoren ermöglicht. Da mit der Transfusion von peripheren Blutstammzellen die Myelosuppression beherrschbar wurde, bestimmt die nichthämatologische Toxizität den Grad der Dosiseskalation.In der Regel wurden Hochdosischemotherapien nach vorausgegangener dosisintensivierter Chemotherapie durchgeführt. Durch die vorgeschaltete Chemotherapie soll einerseits die Chemosensibilität der Tumorerkrankung nachgewiesen und andererseits eine Stammzellmobilisierung bewirkt werden. Früher wurde die Hochdosischemotherapie durch eine autologe Knochenmarktransplantation (AKMT), heute fast ausnahmslos durch die Retransfusion von peripheren Blutstammzellen als spezifische Supportivmaßnahme begleitet. Die peripheren Blutstammzellen werden durch die Apherese der mononukleären Zellfraktion am Zellseparator gesammelt.Nennenswerte Erfahrungen mit der Hochdosischemotherapie beim Erwachsenen liegen für das Mamma-, Hoden-, Ovarial-, kleinzellige Bronchialkarzinom (SCLC), Melanom, Glioblastom und Weichgewebssarkom vor. Die Studien belegen die Durchführbarkeit und Effektivität der Hochdosischemotherapie bei tolerabler Toxizität.Die Hochdosischemotherapie wird zukünftig eine zunehmende Bedeutung in dem primären Chemotherapiekonzept von soliden Tumoren bekommen.The availability of hemopoetic growth factors and the retransfusion of autologous peripheral blood stem cells (PBSC) have enabled high-dose chemotherapy (HDT) options for the treatment of advanced solid tumours, during recent years. Though the transfusion of PBSC can manage the myelosuppression, dose-escalation ist still limited by non-haematological toxicity.Usually, HDT has been given after a preceeding dose-intense chemotherapy that allowed the evaluation of chemosensitivity of the disease and resulted in a stem cell mobilization into the peripheral blood. The autologous bone marrow transplantation has almost completely been replaced by retransfusion of PBSC together with hemopoetic growth factors as specific supportive treatment. The PBSC are harvested by apheresis using a blood cell separator.Results on the efficacy of HDT are available for breast, testicular, ovarian, small cell lung cancer as well as melanoma, glioblastoma and soft-tissue sarcoma. The studies showed the feasibility and efficacy of HDT with tolerable toxicity.High-dose chemotherapy will be of increasing importance in the treatment strategies of primary solid tumors, in the near future.
    Keywords: High-dose chemotherapy ; Peripheral blood stem cells ; Solid tumors
    ISSN: 0723-5003
    E-ISSN: 1615-6722
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