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Tytuł pozycji:

Sorafenib and everolimus in patients with advanced solid tumors and KRAS‐mutated NSCLC: A phase I trial with early pharmacodynamic FDG‐PET assessment

Tytuł :
Sorafenib and everolimus in patients with advanced solid tumors and KRAS‐mutated NSCLC: A phase I trial with early pharmacodynamic FDG‐PET assessment
Autorzy :
Lucia Nogova
Christian Mattonet
Matthias Scheffler
Max Taubert
Masyar Gardizi
Martin L. Sos
Sebastian Michels
Rieke N. Fischer
Meike Limburg
Diana S.Y. Abdulla
Thorsten Persigehl
Carsten Kobe
Sabine Merkelbach‐Bruse
Jeremy Franklin
Heiko Backes
Roland Schnell
Dirk Behringer
Britta Kaminsky
Martina Eichstaedt
Christoph Stelzer
Martina Kinzig
Fritz Sörgel
Yingying Tian
Lisa Junge
Ahmed A. Suleiman
Sebastian Frechen
Dennis Rokitta
Dongsheng Ouyang
Uwe Fuhr
Reinhard Buettner
Jürgen Wolf
Pokaż więcej
Temat :
FDG‐PET
KRAS mutation
non‐small‐cell lung cancer
pharmacodynamics
pharmacokinetics
Phase‐I trial
Neoplasms. Tumors. Oncology. Including cancer and carcinogens
RC254-282
Źródło :
Cancer Medicine, Vol 9, Iss 14, Pp 4991-5007 (2020)
Informacja o wydawcy :
Wiley, 2020.
Rok publikacji :
2020
Kolekcja :
LCC:Neoplasms. Tumors. Oncology. Including cancer and carcinogens
Typ dokumentu :
article
Opis pliku :
electronic resource
Język :
English
ISSN :
2045-7634
70742839
Relacje :
https://doaj.org/toc/2045-7634
DOI :
10.1002/cam4.3131
Dostęp URL :
https://doaj.org/article/04f6918ff70742839866e3f4fa056a57
Numer akcesji :
edsdoj.04f6918ff70742839866e3f4fa056a57
Czasopismo naukowe
Abstract Background Treatment of patients with solid tumors and KRAS mutations remains disappointing. One option is the combined inhibition of pathways involved in RAF‐MEK‐ERK and PI3K‐AKT‐mTOR. Methods Patients with relapsed solid tumors were treated with escalating doses of everolimus (E) 2.5‐10.0 mg/d in a 14‐day run‐in phase followed by combination therapy with sorafenib (S) 800 mg/d from day 15. KRAS mutational status was assessed retrospectively in the escalation phase. Extension phase included KRAS‐mutated non–small‐cell lung cancer (NSCLC) only. Pharmacokinetic analyses were accompanied by pharmacodynamics assessment of E by FDG‐PET. Efficacy was assessed by CT scans every 6 weeks of combination. Results Of 31 evaluable patients, 15 had KRAS mutation, 4 patients were negative for KRAS mutation, and the KRAS status remained unknown in 12 patients. Dose‐limiting toxicity (DLT) was not reached. The maximum tolerated dose (MTD) was defined as 7.5 mg/d E + 800 mg/d S due to toxicities at previous dose level (10 mg/d E + 800 mg/d S) including leucopenia/thrombopenia III° and pneumonia III° occurring after the DLT interval. The metabolic response rate in FDG‐PET was 17% on day 5 and 20% on day 14. No patient reached partial response in CT scan. Median progression free survival (PFS) and overall survival (OS) were 3.25 and 5.85 months, respectively. Conclusions Treatment of patients with relapsed solid tumors with 7.5 mg/d E and 800 mg/d S is safe and feasible. Early metabolic response in FDG‐PET was not confirmed in CT scan several weeks later. The combination of S and E is obviously not sufficient to induce durable responses in patients with KRAS‐mutant solid tumors.
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