Bevacizumab plus capecitabine as a salvage therapy in advanced adrenocortical carcinoma

Wortmann, Sebastian; Quinkler, Marcus; Ritter, Christian; Kroiß, Matthias; Johanssen, Sarah; Hahner, Stefanie; Allolio, Bruno; Fassnacht, Martin

doi:10.1530/eje-09-0804

Cited by 111 publications

(66 citation statements)

References 36 publications

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“…Similar to our data, all patients showed a disease progression (25). However, our in vitro study showed that ACC cells are sensitive to sorafenib administration.…”

Section: Discussionsupporting

confidence: 91%

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

Berruti

Sperone

Ferrero

et al. 2012

European Journal of Endocrinology

122

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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/m 2 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. 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.

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“…Similar to our data, all patients showed a disease progression (25). However, our in vitro study showed that ACC cells are sensitive to sorafenib administration.…”

Section: Discussionsupporting

confidence: 91%

“…In a multicenter phase II trial previously done in Germany, ten patients who were heavily pretreated with three or more therapeutic lines received a combination of bevacizumab and capecitabine administered on a metronomic schedule (25). Similar to our data, all patients showed a disease progression (25).…”

Section: Discussionsupporting

confidence: 86%

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

Berruti

Sperone

Ferrero

et al. 2012

European Journal of Endocrinology

122

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“…[29][30][31][32][33][34] The tumor response in our study compares favorably with the results obtained with these novel therapies. Nonetheless, the poor overall survival rates in our study confirm the poor prognosis for patients with advanced adrenocortical carcinoma and the need for improved treatment options.…”

Section: Discussionsupporting

confidence: 68%

Combination Chemotherapy in Advanced Adrenocortical Carcinoma

Fassnacht¹,

Terzolo²,

Allolio³

et al. 2012

N Engl J Med

Self Cite

706

502

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“…As a matter of fact, drugs or combination regimens tested previously in this clinical setting did not show any relevant clinical activity (Baudin et al 2002, Khan et al 2004, Quinkler et al 2008, Wortmann et al 2009). Thus, heavily pretreated ACC patients are left with a poor life expectancy.…”

Section: Discussionmentioning

confidence: 90%

“…On these premises, many patients submitted to chemotherapy and mitotane are expected to fail or progress after initial response, and there is, therefore, an urgent need for salvage therapy. At the present time, a few experiences regarding the role of second-and thirdline therapy for refractory ACC have shown disappointing results (Baudin et al 2002, Khan et al 2004, Quinkler et al 2008, Wortmann et al 2009). At the Consensus Conference held in Ann Arbor in 2003 (Schteingart et al 2005), gemcitabine was considered among the most promising agents.…”

Section: Introductionmentioning

confidence: 99%

Gemcitabine plus metronomic 5-fluorouracil or capecitabine as a second-/third-line chemotherapy in advanced adrenocortical carcinoma: a multicenter phase II study

Sperone¹,

Ferrero²,

Daffara³

et al. 2010

Endocrine-Related Cancer

138

100

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Adrenocortical carcinoma (ACC) is a rare neoplasm characterized by poor prognosis. First-line systemic treatments in advanced disease include mitotane, either alone or in combination with chemotherapy. Studies evaluating second-line therapy options have obtained disappointing results. This trial assessed the activity and toxicity of gemcitabine plus metronomic fluoropyrimidines in heavily pretreated advanced ACC patients. From 1998 to 2008, 28 patients with advanced ACC progressing after mitotane plus one or two systemic chemotherapy lines were enrolled. They received a combination of i.v. gemcitabine (800 mg/m 2 , on days 1 and 8, every 21 days) and i.v. 5-fluorouracil protracted infusion (200 mg/m 2 /daily without interruption until progression) in the first six patients, or oral capecitabine (1500 mg/daily) in the subsequent patients. Mitotane administration was maintained in all cases. The rate of non-progressing patients after 4 months of treatment was 46.3%. A complete response was observed in 1 patient (3.5%); 1 patient (3.5%) obtained a partial regression, 11 patients (39.3%) obtained a disease stabilization and 15 patients (53.7%) progressed. Treatment was well tolerated, with grade III and IV toxicities consisting of leukopenia in six patients (21.4%), thrombocytopenia in one patient (3.5%), and mucositis in one patient (3.5%). Median time to progression and overall survival in the patient population were 5.3 (range: 1-43) and 9.8 months (range: 3-73) respectively. Gemcitabine plus metronomic fluoropyrimidines is a well-tolerated and moderately active regimen in heavily pretreated ACC patients.

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Bevacizumab plus capecitabine as a salvage therapy in advanced adrenocortical carcinoma

Abstract: Objective: No standard therapy for advanced adrenocortical carcinoma

Cited by 111 publications

References 36 publications

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

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

Combination Chemotherapy in Advanced Adrenocortical Carcinoma

Gemcitabine plus metronomic 5-fluorouracil or capecitabine as a second-/third-line chemotherapy in advanced adrenocortical carcinoma: a multicenter phase II study

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