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Hepatoprotective effect of N-acetylcysteine in trabectedin-induced liver toxicity in patients with advanced soft tissue sarcoma

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Abstract

Purpose

Trabectedin is one of the few active agents in soft tissue sarcoma (STS) but hepatotoxicity is frequent and represents a dose-limiting factor. Protective strategies aiming at counteracting this important side effect have a crucial clinical impact. Due to its antioxidant properties, N-acetylcysteine (NAC) has a recognized hepatoprotective effect and this provides the rationale for testing NAC in the management of trabectedin-induced hepatotoxicity.

Methods

Patients with recurrent or metastatic soft tissue sarcoma, consecutively observed at our institution, who were considered eligible to trabectedin, received concomitant NAC if they had impaired hepatic or renal function at baseline or developed hepatotoxicity during treatment. The study aim was to retrospectively explore trabectedin administration in terms of number of cycles, mean dose, and dose intensity (DI) in patients who received NAC as compared with those who did not. Secondary end points were progression-free survival (PFS) and overall survival (OS).

Results

A total number of 18 patients were enrolled in this study. Nine received NAC and nine did not. The median number of administered trabectedin cycles, mean trabectedin dose/cycles, and median DI was comparable in the two groups (p = 0.450, p = 0.534, and p = 0.450, respectively). The PFS and OS curves overlapped.

Conclusion

This explorative study suggests that NAC can have a hepatoprotective activity in patients receiving trabectedin allowing to maintain an adequate dose intensity and continuative administration in patients with impaired liver and renal function or developing treatment-induced hepatotoxicity. A prospective randomized trial is warranted.

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Funding

The study was supported in part by donations of “gli Amici di Carlo” in memory of Carlo Ridon, “gli Amici di Andrea” in memory of Andrea Gadeschi, and “gli Amici di Marco Treccani” in memory of Marco Treccani.

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Authors and Affiliations

  1. Dipartimento di Specialità Medico-Chirurgiche, Scienze Radiologiche e Sanità Pubblica, Oncologia Medica, Università degli Studi di Brescia, ASST Spedali Civili, Brescia, Italy

    Salvatore Grisanti, Deborah Cosentini, Valeria Tovazzi, Susanna Bianchi, Barbara Lazzari, Francesca Consoli, Elisa Roca, Alfredo Berruti & Vittorio D Ferrari

  2. Oncologia Medica, ASST Spedali Civili, Piazzale Spedali Civili 1, 20123, Brescia, Italy

    Alfredo Berruti

Authors
  1. Salvatore Grisanti
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  2. Deborah Cosentini
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  3. Valeria Tovazzi
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  4. Susanna Bianchi
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  5. Barbara Lazzari
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  6. Francesca Consoli
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  7. Elisa Roca
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  8. Alfredo Berruti
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  9. Vittorio D Ferrari
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Corresponding author

Correspondence to Alfredo Berruti.

Ethics declarations

The retrospective collection and analyses of data were approved by the Ethical Review Board of the Spedali Civili Hospital, Brescia, Italy (No. 0042053). A written informed consent was signed by all patients that were alive at the collection.

Conflict of interest

The authors declare that they have no conflict of interest.

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Grisanti, S., Cosentini, D., Tovazzi, V. et al. Hepatoprotective effect of N-acetylcysteine in trabectedin-induced liver toxicity in patients with advanced soft tissue sarcoma. Support Care Cancer 26, 2929–2935 (2018). https://doi.org/10.1007/s00520-018-4129-x

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  • DOI: https://doi.org/10.1007/s00520-018-4129-x

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