Phase II study of weekly paclitaxel and sorafenib as second/third-line therapy in patients with adrenocortical carcinoma

BackgroundThere 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.ObjectiveWe assessed the activity of sorafenib plus met...

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Published in:European journal of endocrinology 2012-03, Vol.166 (3), p.451-458
Main Authors: Berruti, Alfredo, Sperone, Paola, Ferrero, Anna, Germano, Antonina, Ardito, Arianna, Priola, Adriano Massimiliano, De Francia, Silvia, Volante, Marco, Daffara, Fulvia, Generali, Daniele, Leboulleux, Sophie, Perotti, Paola, Baudin, Eric, Papotti, Mauro, Terzolo, Massimo
Format: Article
Language:English
Subjects:
Adrenal Cortex Neoplasms - drug therapy
Adrenal Cortex Neoplasms - pathology
Adrenals. Adrenal axis. Renin-angiotensin system (diseases)
Adrenocortical Carcinoma - drug therapy
Adrenocortical Carcinoma - pathology
Adult
Aged
Antineoplastic Combined Chemotherapy Protocols - administration & dosage
Benzenesulfonates - administration & dosage
Biological and medical sciences
Cell Line, Tumor
Clinical Study
Disease-Free Survival
Drug Administration Schedule
Endocrinopathies
Female
Follow-Up Studies
Fundamental and applied biological sciences. Psychology
Humans
Male
Malignant tumors
Medical sciences
Middle Aged
Niacinamide - analogs & derivatives
Paclitaxel - administration & dosage
Phenylurea Compounds
Prospective Studies
Pyridines - administration & dosage
Vertebrates: endocrinology
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Summary:BackgroundThere 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.ObjectiveWe 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.DesignMulticenter, prospective phase II trial.SettingReferral centers for ACC.MethodsTwenty-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/m2 every 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.ResultsTumor 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.ConclusionsDespite the in vitro activity, sorafenib plus weekly paclitaxel is an inactive salvage treatment in patients with advanced ACC and should not be recommended.
ISSN:0804-4643
1479-683X
DOI:10.1530/EJE-11-0918