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  • Therapy of mRCC beyond mTOR-inhibition in clinical practice: results of a retrospective analysis.

Therapy of mRCC beyond mTOR-inhibition in clinical practice: results of a retrospective analysis.

Journal of cancer research and clinical oncology (2014-02-22)
Luise Maute, Viktor Grünwald, Steffen Weikert, Ulrich Kube, Thomas Gauler, Christoph Kahl, Iris Burkholder, Lothar Bergmann
ABSTRACT

Renal cell carcinoma (RCC) is the most common renal tumor and accounts for nearly 3 % of adult cancers. In the recent years, seven new targeted agents have been approved changing the treatment in metastatic RCC dramatically. So far, however, it remains unclear which sequence is best for those patients. This study analyzed retrospectively the outcome of patients treated with everolimus after failure of a vascular endothelial growth factor receptor-directed therapy and which therapies were used after everolimus. In a retrospective analysis, patients receiving everolimus after failure of first-line VEGFR-directed therapy have been analyzed in regard to response, duration of treatment and subsequent therapies. In total, the data of 81 patients have been analyzed. The most observed first-line therapy was sunitinib followed by sorafenib. Thirty-two patients received everolimus as second-line therapy, and 49 as third-line therapy. The median duration of treatment with everolimus was 4.5 months. Seventy-seven of eighty-one patients (95 %) received a further therapy after discontinuation of everolimus. The agents administered beyond were sunitinib (28.6 %), sorafenib (28.6 %) and 42.8 % received other therapies. Twenty-seven patients received an additional sequence of therapy (fourth to fifth line). Fifty-eight percentage of patients have still been alive at time of analysis. The duration of everolimus therapy beyond failure of anti-VEGF-directed therapy and the reported time to progression was in the range of the RECORD-1 trial in daily practice as well. After failure of everolimus, reexposure to tyrosine kinase inhibitors is a common clinical practice and demonstrates a clinical benefit of therapies beyond everolimus.

MATERIALS
Product Number
Brand
Product Description

Supelco
Everolimus solution, 1.0 mg/mL in acetonitrile, ampule of 1 mL, certified reference material, Cerilliant®
Supelco
Sirolimus solution, 1.0 mg/mL in acetonitrile, ampule of 1 mL, certified reference material, Cerilliant®
Sigma-Aldrich
Rapamycin from Streptomyces hygroscopicus, ≥95% (HPLC), powder
Supelco
Rapamycin, VETRANAL®, analytical standard
Supelco
Niacinamide, Pharmaceutical Secondary Standard; Certified Reference Material
Nicotinamide, European Pharmacopoeia (EP) Reference Standard
Sigma-Aldrich
Nicotinamide, BioReagent, suitable for cell culture, suitable for insect cell culture
Sigma-Aldrich
Nicotinamide, ≥98.5% (HPLC)
Sigma-Aldrich
Nicotinamide, ≥99.5% (HPLC)
Sigma-Aldrich
Nicotinamide, ≥98% (HPLC), powder
Sigma-Aldrich
Niacinamide, meets USP testing specifications
USP
Niacinamide, United States Pharmacopeia (USP) Reference Standard
Supelco
Nicotinamide (Vitamin B3) solution, 1.0 mg/mL in methanol, ampule of 1 mL, certified reference material, Cerilliant®