| Autor: |
Berruti, Alfredo, Sperone, Paola, Ferrero, Anna, Germano, Antonina, Ardito, Arianna, Priola, Adriano Massimiliano, Francia, Silvia De, Volante, Marco, Daffara, Fulvia, Generali, Daniele, Leboulleux, Sophie, Perotti, Paola, Baudin, Eric, Papotti, Mauro, Terzolo, Massimo |
| Předmět: |
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| Zdroj: |
European Journal of Endocrinology; Mar2012, Vol. 166 Issue 3, p451-458, 8p, 2 Charts, 2 Graphs |
| Abstrakt: |
BACKGROUND: There is a strong rationale in the use of antiangiogenic therapy in the management of adrenocortical carcinoma (ACC). Metronomic administration of chemotherapy and antiangiogenic drugs can be synergistic in targeting endothelial cells. OBJECTIVE: We assessed the activity of sorafenib plus metronomic paclitaxel as second/third-line therapy in advanced ACC patients. We also tested the activity of sorafenib and paclitaxel against NCI-H295R in vitro. DESIGN: Multicenter, prospective phase II trial. SETTING: Referral centers for ACC. METHODS: Twenty-five consecutive metastatic ACC patients who progressed after mitotane plus one or two chemotherapy lines were planned to be enrolled. The patients received a combination of i.v. paclitaxel (60 mg/m2every week) and oral sorafenib (400 mg twice a day) till progression. The primary aim was to measure the progression-free survival rate after 4 months and the secondary aims were to assess the objective response rate and toxicity. RESULTS: Tumor progression was observed in nine evaluable patients at the first assessment. These results led to the premature interruption of the trial. The treatment was well tolerated. The most relevant toxicities were fatigue, being grade 2 or 3 in four patients, and hypophosphatemia, being grade 3 in three patients. In the in vitro study, sorafenib impaired the viability of H295R cells with dose–response and time–response relationships. The in vitro sorafenib activity was not increased in combination with paclitaxel. CONCLUSIONS: Despite the in vitro activity, sorafenib plus weekly paclitaxel is an inactive salvage treatment in patients with advanced ACC and should not be recommended. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
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