Sorafenib and dacarbazine in soft tissue sarcoma: A single institution experience

Bruno Vincenzi, Marianna Silletta, Gaia Schiavon, Anna Maria Frezza, Raimondo Del Vescovo, Bruno Beomonte Zobel, Daniele Santini, Angelo Paolo Dei Tos, Giuseppe Tonini

Research output: Contribution to journalArticle

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Abstract

Background: To report on the anti-tumour activity and toxicity of sorafenib combined with dacarbazine in patients with pre-treated advanced soft tissue sarcoma (STSs). Methods: From November 2009 to December 2010, 17 patients affected by STSs who had failed two or more regimen of chemotherapy, with a performance status ≤ 2 and measurable disease were consecutively enrolled in the present case series. Sorafenib was administered at 400 mg b.i.d. continuous dosing in combination with dacarbazine, 300 mg/m2 for three consecutive days every 21 days until disease progression or intolerable toxicity. Results: Fourteen patients were evaluable for response. Three patients stopped treatment early and were not evaluable for response. One of them died for not disease-dependent reason, the other two went off-study due to rapid clinical worsening, without performing radiologic evaluation. No complete responses were registered. As by RECIST, partial responses (PR) were observed in three patients (21%), stable disease (SD) in six patients (43%) and progressive disease (PD) in five patients (36%), with a clinical benefit rate (RECIST PR±SD > 6 months) of 64%. The median time of progression was 20 weeks (range: 9-34 weeks) and the median overall survival was 43 weeks (range: 17-65 weeks). The main toxicities were neutropenia (36%), thrombocytopenia (36%), hypertension (36%), fatigue (50%) and skin reactions (57%). Five patients required dose reductions (both dacarbazine and sorafenib) for toxicity and three patients required only sorafenib reduction for dermatologic reactions. One patient was taken off-study because of severe sorafenib-related dermatologic toxicity. Conclusions: Sorafenib and dacarbazine combination seems to be an active and safety regimen in pre-treated STSs. A Phase II trial is ongoing in patient affected by selected sarcoma subtypes.

Original languageEnglish
Pages (from-to)1-7
Number of pages7
JournalExpert Opinion on Investigational Drugs
Volume22
Issue number1
DOIs
Publication statusPublished - Jan 2013

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Dacarbazine
Sarcoma
sorafenib
Neutropenia
Thrombocytopenia
Fatigue
Disease Progression

Keywords

  • Dacarbazine
  • Pre-treated soft tissue sarcoma
  • Sorafenib

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)

Cite this

Sorafenib and dacarbazine in soft tissue sarcoma : A single institution experience. / Vincenzi, Bruno; Silletta, Marianna; Schiavon, Gaia; Frezza, Anna Maria; Del Vescovo, Raimondo; Zobel, Bruno Beomonte; Santini, Daniele; Dei Tos, Angelo Paolo; Tonini, Giuseppe.

In: Expert Opinion on Investigational Drugs, Vol. 22, No. 1, 01.2013, p. 1-7.

Research output: Contribution to journalArticle

Vincenzi, B, Silletta, M, Schiavon, G, Frezza, AM, Del Vescovo, R, Zobel, BB, Santini, D, Dei Tos, AP & Tonini, G 2013, 'Sorafenib and dacarbazine in soft tissue sarcoma: A single institution experience', Expert Opinion on Investigational Drugs, vol. 22, no. 1, pp. 1-7. https://doi.org/10.1517/13543784.2013.742886
Vincenzi, Bruno ; Silletta, Marianna ; Schiavon, Gaia ; Frezza, Anna Maria ; Del Vescovo, Raimondo ; Zobel, Bruno Beomonte ; Santini, Daniele ; Dei Tos, Angelo Paolo ; Tonini, Giuseppe. / Sorafenib and dacarbazine in soft tissue sarcoma : A single institution experience. In: Expert Opinion on Investigational Drugs. 2013 ; Vol. 22, No. 1. pp. 1-7.
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abstract = "Background: To report on the anti-tumour activity and toxicity of sorafenib combined with dacarbazine in patients with pre-treated advanced soft tissue sarcoma (STSs). Methods: From November 2009 to December 2010, 17 patients affected by STSs who had failed two or more regimen of chemotherapy, with a performance status ≤ 2 and measurable disease were consecutively enrolled in the present case series. Sorafenib was administered at 400 mg b.i.d. continuous dosing in combination with dacarbazine, 300 mg/m2 for three consecutive days every 21 days until disease progression or intolerable toxicity. Results: Fourteen patients were evaluable for response. Three patients stopped treatment early and were not evaluable for response. One of them died for not disease-dependent reason, the other two went off-study due to rapid clinical worsening, without performing radiologic evaluation. No complete responses were registered. As by RECIST, partial responses (PR) were observed in three patients (21{\%}), stable disease (SD) in six patients (43{\%}) and progressive disease (PD) in five patients (36{\%}), with a clinical benefit rate (RECIST PR±SD > 6 months) of 64{\%}. The median time of progression was 20 weeks (range: 9-34 weeks) and the median overall survival was 43 weeks (range: 17-65 weeks). The main toxicities were neutropenia (36{\%}), thrombocytopenia (36{\%}), hypertension (36{\%}), fatigue (50{\%}) and skin reactions (57{\%}). Five patients required dose reductions (both dacarbazine and sorafenib) for toxicity and three patients required only sorafenib reduction for dermatologic reactions. One patient was taken off-study because of severe sorafenib-related dermatologic toxicity. Conclusions: Sorafenib and dacarbazine combination seems to be an active and safety regimen in pre-treated STSs. A Phase II trial is ongoing in patient affected by selected sarcoma subtypes.",
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AU - Del Vescovo, Raimondo

AU - Zobel, Bruno Beomonte

AU - Santini, Daniele

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