Prospective comparison of sorafenib and sunitinib for second-line treatment of cytokine-refractory kidney cancer patients.
ABSTRACT It was the aim of this study to investigate the clinical differences between the tyrosine kinase inhibitors (TKIs) sorafenib and sunitinib as second-line treatment for cytokine-refractory kidney cancer patients.
Twenty consecutive patients received continuous treatment of oral sorafenib at a dose of 400 mg twice daily in 6-week cycles. Sunitinib was administered to the remaining 20 patients at 50 mg once daily in repeated 6-week cycles consisting of daily therapy for 4 weeks, followed by a 2-week off-treatment period. We correlated best treatment responses and progression-free survival (PFS) with either TKI treatment. Adverse events were evaluated and differences were compared between both treatment groups.
In the sorafenib group, 2 (10%) patients showed a partial response (PR) and 4 (20%) patients had progressive disease (PD) versus 6 (30%) PRs and 3 (15%) PDs in the sunitinib group, respectively (p = 0.195). The median PFS was 6.4 months for sorafenib and 7.4 months for sunitinib (p = 0.969). In contrast to gender, age and the number of prior cytokine therapy cycles, the Eastern Cooperative Oncology Group performance status (p = 0.024) and the Memorial Sloan-Kettering Cancer Center risk groups for second-line treatments (p = 0.015) were independent predictive parameters of PFS. Gastrointestinal symptoms were found to occur with greater frequency in the sunitinib group (p = 0.03).
Both TKIs showed comparable clinical benefits. The Eastern Cooperative Oncology Group performance status and the Memorial Sloan-Kettering Cancer Center risk groups can help determine which patients might benefit from alternative drug treatments.
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ABSTRACT: Optimal long-lasting treatment with sunitinib and sorafenib is limited by dose modifications (DMs) due to adverse events (AEs). These AEs may be underrecognized and their influence on health-related quality of life (HRQL) underestimated. Improved insight into the relationship between AEs and therapy decisions is needed. To improve decision making around managing symptoms and reduce DMs, this study was set up to explore the influence of patient-reported symptoms on therapy decisions. In this multicenter cohort study, patient characteristics, reasons for and different forms of used dose modifications, and AEs were prospectively obtained from cancer patients on sunitinib/sorafenib treatment. Used instruments to get insight into AEs were the patient-scored Utrecht Symptom Diary (USD) and the professional-scored Common Terminology Criteria for AEs version 3.0. Median total treatment duration in 42 patients was 16 weeks. Median time till dose modification was 10 weeks. DMs occurred mostly due to multiple mild AEs. By using the USD, a higher prevalence of most AEs was found compared to the literature. Sixty percent of the patients experienced a decreased HRQL due to multiple AEs. Because severe AEs due to sunitinib/sorafenib treatment seldom occur, it is more important to focus on treating and preventing multiple mild AEs with higher impact on HRQL, when trying to avoid dose modifications. Using patient self-reported measurement methods helps to early recognize symptoms and to differentiate among symptom intensities. This systematic approach might help to achieve the optimal dosing, which might improve PFS and OS.Supportive Care in Cancer 04/2014; DOI:10.1007/s00520-014-2223-2 · 2.09 Impact Factor
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ABSTRACT: Die letzten 5Jahre waren durch grundlegende Veränderungen in der Systemtherapie des metastasierten Nierenzellkarzinoms gekennzeichnet. Noch bis Ende der letzten Dekade war die Zytokin-basierte Chemotherapie die einzige, wenn auch mäßig erfolgreiche Systemtherapie zur Behandlung der metastasierten Stadien. Mit Everolimus (Afinitor®) sind in Deutschland aktuell 5 neue sog. Targetsubstanzen zugelassen, denen ein letztlich molekular basierter therapeutischer Mechanismus zugrunde liegt. Sunitinib (Sutent®) und Sorafenib (Nexavar®) als Multikinaseinhibitoren, Everolimus (Afinitor®) und Temsirolimus (Torisel®) als mTOR-Inhibitoren und Bevacizumab als Antikörper gegen VEGF in Kombination mit Interferon-α (IFN-α). Die folgende kompakte Zusammenfassung soll einen aktuellen Überblick über die zugelassenen Substanzen geben, kritische Überlegungen zur Therapieplanung diskutieren, sowie einen Ausblick in die Zukunft bieten. The past 5 years were marked by fundamental changes in the systemic therapy of metastatic renal cell carcinoma. Up to the end of the last decade cytokine-based chemotherapy was the only, even if only moderately effective systemic therapy for metastatic renal cell carcinoma. Currently there are five new approved drug releases of so-called targeted substances, which function on a molecular based therapeutic mechanism. Sunitinib (Sutent®) and sorafenib (Nexavar®) as multikinase inhibitors, everolimus (Afinitor®) and temsirolimus (Torisel®) as mTOR inhibitors, and bevacizumab as an antibody against VEGF in combination with interferon-alpha (IFN-α). The following article will give an overview of the currently available substances and critically discuss therapy plans and future trends.Der Urologe 09/2009; 48(9):983-989. DOI:10.1007/s00120-009-2072-7 · 0.44 Impact Factor
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ABSTRACT: The aim of the present study was to investigate the available literature regarding the oral side effects or adverse events associated with targeted cancer therapy. Common oral toxicities include the terms mucositis, stomatitis, dysphagia, xerostomia, pharyngitis, and taste alterations. Aims of treatment included molecules and pathways involved in carcinogenesis reported in the literature were EGFRI, VEGF, mTOR, mAbs, TKIs, and multi-kinase inhibitors. Common targeted therapies used in clinical practice or under-investigation included cetuximab, panitumumab, erlotinib, sorafenib, sunitinib malate, imatinib mesylate, bevacizumab, trastuzumab, lapatinib, and mTORs. One hundred and forty-three articles were considered relevant and included in this review. The majority of studies did not specifically address oral toxicities or include an oral clinical exam, which may lead to underreported and under-investigated oral toxicities. Further investigation is necessary to determine if the initial impression that targeted therapy produces milder oral toxicities than conventional cancer treatment is accurate.Oral Oncology 06/2011; 47(6):441-8. DOI:10.1016/j.oraloncology.2011.03.028 · 3.03 Impact Factor