Your email was sent successfully. Check your inbox.

An error occurred while sending the email. Please try again.

Proceed reservation?

  • 1
    German Medical Science GMS Publishing House; Düsseldorf
    In:  GMS German Medical Science; VOL: 7; DOC04 /20090610/
    Publication Date: 2009-06-11
    Description: Background: The highly vascular nature of renal carcinoma cells suggests that inhibition of angiogenesis may be beneficial in this disease. Thalidomide has been described as inhibitor of the fibroblast growth factor (FGF) and the vascular endothelial growth factor (VEGF). Therefore and in consideration of the promising response rates of the combination of IL-2, IFN-alpha and 5-FU in metastatic renal cancer, we found it reasonable to test the combination of 5-FU and thalidomide. Thus, we conducted a phase I trial to determine safety, side effects and responses to such a treatment. Methods: Patients with metastasized renal cell cancer after nephrectomy and progress after IL-2 and interferon treatment, received oral 5-FU at a dose of 1250 mg/qm2 twice a day for two weeks, then after pausing a week, the oral application was restarted. In addition, oral thalidomide was applied constantly at a maximum dose of 400 mg/d. The combined therapy was given for three months. The primary endpoint was duration until disease progression, the secondary endpoint the response to treatment. Response was determined by CT scans three months after the end of treatment. Results: In total, 12 male patients participated in the trial and received the combined oral therapy. Concerning clinical response, one mixed response (8%), a stable disease in 4/12 patients (33%) and progression was seen in 7 patients (58%). The survival from the start of the therapy showed a median of 21 months with three patients being alive. At present, the longest survival after the therapy is 51 months. Conclusions: The combination of oral 5-FU and thalidomide showed clinical response with tolerable side effects. Further studies will be required to assess the outcome of this treatment regimen.
    Description: Hintergrund: Die hohe Vaskularisierung beim Nierenzellkarzinom legt nahe, dass eine Inhibition der Angiogenese bei dieser Erkrankung von Vorteil sein könnte. Thalidomid wurde als Inhibitor von FGF (Fibroblastenwachstumsfaktor) und VEGF (vaskulärer endothelialer Wachstumsfaktor) beschrieben. Deshalb und aufgrund der erfolgversprechenden Daten von Interleukin-2, Interferon-alpha und 5-FU testeten wir die Kombination von Thalidomid und 5-FU. Wir führten eine Phase-I-Studie zur Testung von Sicherheit und Verträglichkeit durch. Methoden: Patienten mit metastasiertem Nierenzellkarzinom nach Nephrektomie und Progress nach IL-2 und Interferon-Behandlung erhielten orales 5-FU in einer Dosierung von 1250 mg/qm2 zweimal täglich über 2 Wochen. Nach einer einwöchigen Pause, wurde die Behandlung fortgesetzt. Zusätzlich wurde Thalidomid kontinuierlich bis zu einer maximalen Dosis von 400 mg/Tag gegeben. Diese Kombination erhielten die Patienten über 3 Monate. Primärer Endpunkt war die Dauer bis zur Progression der Krankheit, sekundärer Endpunkt das Ansprechen auf die Therapie. Das Ansprechen wurde mittels CT 3 Monate nach Ende der Therapie bestimmt. Ergebnisse: 12 männliche Patienten nahmen an dieser Studie teil. Ein gemischtes Ansprechen (8%), 4 stabile Erkrankungen (33%) und 〈TextGroup〉 7 Pr 〈/TextGroup〉ogresse (58%) wurden gesehen. Das mittlere Überleben betrug 21 Monate mit jetzt noch 3 lebenden Patienten. Zur Zeit beträgt das längste Überleben 51 Monate. Schlussfolgerung: Die Kombination von oralem 5-FU und Thalidomid zeigte bei diesen überwiegend vortherapierten Patienten klinisches Ansprechen bei tolerablen Nebenwirkungen. Weitere Studien sind notwendig, um den Stellenwert dieser Kombination nach Gabe der neuen Therapieoptionen beim metastasierten Nierenzellkarzinom zu untersuchen.
    Keywords: metastasized renal cell carcinoma ; 5-FU ; thalidomide ; phase I trial ; ddc: 610
    Language: English
    Type: article
    Signatur Availability
    BibTip Others were also interested in ...
  • 2
    Abstract: The objective was to evaluate the prognostic and predictive impact of allelic ratio and insertion site (IS) of internal tandem duplications (ITD), as well as concurrent gene mutations with regard to postremission therapy in 323 patients with FLT3-ITD positive acute myeloid leukemia (AML). Increasing FLT3-ITD allelic ratio (p=0.004) and IS in the tyrosine kinase domain 1 (TKD1, p=0.06) were associated with low complete remission (CR) rates. After postremission therapy including intensive chemotherapy (CTX, n=121) or autologous hematopoietic stem cell transplantation (HSCT, n=17), an allelic ratio 〉/=0.51 was associated with an unfavorable relapse-free (RFS, p=0.0008) and overall survival (OS, p=0.004); after allogeneic HSCT (n=93), outcome was significantly improved in patients with a high allelic ratio (RFS, p=0.02; OS, p=0.03), whereas no benefit was seen in patients with low allelic ratio (RFS, p=0.38; OS, p=0.64). Multivariable analyses revealed a high allelic ratio as a predictive factor for the beneficial effect of allogeneic HSCT; ITD IS in TKD1 remained an unfavorable factor, whereas no prognostic impact of concurrent gene mutations was observed. The clinical trials described herein were previously published or are registered as follows: AML HD93, reference 29; AML HD98A, reference 30; AMLSG 07-04, identifier: NCT00151242.
    Type of Publication: Journal article published
    PubMed ID: 25270908
    Signatur Availability
    BibTip Others were also interested in ...
Close ⊗
This website uses cookies and the analysis tool Matomo. More information can be found here...