Efficacy of trabectedin in advanced soft tissue sarcoma: beyond lipo- and leiomyosarcoma

Sanctis, Rita De; Marrari, Andrea; Marchetti, Serena; Mussi, Chiara; Balzarini, Luca; Lutman, Fabio Romano; Daolio, Primo Andrea; Bastoni, Stefano; Bertuzzi, Alexia; Quagliuolo, Vittorio; Santoro, Armando

doi:10.2147/dddt.s92395

Cited by 37 publications

(23 citation statements)

References 23 publications

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“…The efficacy of this drug in STS, in particular the myxoid liposarcoma histotype, has been demonstrated in numerous clinical trials, but there are also reports of its activity in other sarcoma subtypes. 53 – 55 Although, there is limited evidence of the impact of trabectedin on MFS, 56 our results are suggestive of some activity in this STS subtype. Moreover, its antitumor activity appears to be related to its direct effect on both cancer cells and the tumor microenvironment.…”

Section: Discussionmentioning

confidence: 58%

Myxofibrosarcoma primary cultures: molecular and pharmacological profile

et al. 2017

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Background:Myxofibrosarcoma (MFS), formerly considered as a myxoid variant of malignant fibrous histiocytoma, is the most common sarcoma of the extremities in adults and is characterized by a high frequency of local recurrence. The clinical behavior of MFS is unpredictable and the efficacy of chemotherapy is still not well documented. Furthermore, given the relatively recent recognition of MFS as a distinct pathologic entity its cellular and molecular biology has still not been extensively studied in patient-derived preclinical models. We examined the molecular biology and treatment outcomes of high-grade, patient-derived MFS primary cultures.Methods:A total of three patient-derived MFS primary cultures were analyzed. We evaluated the role of CD109 expression and also looked for a correlation between transforming growth factor-beta (TGF-β) expression and sensitivity of the primary cultures to different drugs.Results:CD109 was a promising marker for the identification of more aggressive high-grade MFS and a potential therapeutic target. The results also highlighted the potential role of TGF-β in chemoresistance. Pharmacological analysis confirmed the sensitivity of the cultures to chemotherapy. The most active treatments were epirubicin alone and epirubicin in combination with ifosfamide, the latter representing the current standard of care for soft tissue sarcomas (STSs), including MFS.Conclusions:Our results provide a starting point for further research aimed at improving the management of MFS patients undergoing chemotherapy.

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Section: Discussionmentioning

confidence: 58%

Myxofibrosarcoma primary cultures: molecular and pharmacological profile

et al. 2017

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“…This result is supported by the findings of Sanctis et al, who found that a GMI > 1.33 was associated with significantly improved OS. 15,22 Therefore, the growth-inhibitory effect of trabectedin may have a significant impact on longer patient survival.…”

Section: Discussionmentioning

confidence: 99%

Efficacy and safety of trabectedin for patients with unresectable and relapsed soft‐tissue sarcoma in Japan: A Japanese Musculoskeletal Oncology Group study

Kobayashi

Iwata

Wakamatsu

et al. 2019

Cancer

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Background Although initial trabectedin (1.2 mg/m2) is safe and effective for patients with translocation‐related sarcoma (TRS) in Japan, its efficacy in other types of soft‐tissue sarcomas (STSs) remains unknown. This study retrospectively investigated its efficacy and safety through postmarketing surveillance of trabectedin in patients with unresectable and relapsed STS. Methods One hundred forty patients received intravenous trabectedin (1.2 mg/m2 on day 1 every 21 days) over the course of 24 hours. The primary endpoint was the efficacy and safety of trabectedin. Results Grade 3 or higher adverse events occurred in 100 patients (71%) and included hepatotoxicity (37.8%), neutropenia (32.8%), and rhabdomyolysis (3.6%). Patients at high risk for grade 3 or higher rhabdomyolysis (36%) were classified by height (≥170.3 cm) and age (≤32 years) through a classification and regression tree model (area under the curve, 0.9). The overall median progression‐free survival (PFS) was 3.7 months; with respect to the histological type, the median PFS was 17.4 months for myxoid liposarcoma, 4.9 months for leiomyosarcoma, 5.6 months for synovial sarcoma, and 3.7 months for dedifferentiated liposarcoma. Histological type (liposarcoma/leiomyosarcoma [L‐sarcoma] and TRS) and grade 3 neutropenia (but not grade 4) were associated with significantly improved PFS after trabectedin treatment (P = .003, P = .04, and P = .001). The median growth modulation index (GMI) was 0.91; 37 patients (36.7%) experienced a GMI > 1.33, and among patients with solitary fibrous tumors and undifferentiated pleomorphic sarcoma, 60% and 42.9%, respectively, had a GMI > 1.33. The median overall survival (OS) was 16.4 months. A GMI > 1.33 was associated with significantly improved OS (P = .0006). Conclusions Initial trabectedin at 1.2 mg/m2 has clinically meaningful benefits for patients with L‐sarcoma and certain histological subtypes of TRS.

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“…Furthermore, some small studies have shown the potential usefulness of the drug for the treatment of specific non-L-type sarcoma histotypes such as synovial sarcoma and solitary fibrous tumors (SFTs). 15 – 18 Trabectedin has also been approved for the treatment of ovarian cancer.…”

Section: Introductionmentioning

confidence: 99%

Update on the role of trabectedin in the treatment of intractable soft tissue sarcomas

Recine¹,

Bongiovanni²,

Riva³

et al. 2017

OTT

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Soft tissue sarcomas (STS) represent a variety of tumors of mesenchymal origin, accounting for about 1% of all adult cancers. This group of tumors comprises over 60 different histotypes with different biology showing different sensitivity to therapeutic agents. For decades, the standard first-line systemic treatment of metastatic STS has comprised anthracycline based-chemotherapy. Second-line therapy options include agents such as ifosfamide, gemcitabine, and pazopanib, but the optimal sequential therapy for the management of metastatic disease has yet to be defined. Trabectedin is one of the new molecules approved for patients in progression after first-line chemotherapy with anthracyclines or for those unfit for these agents. The compound is characterized by multiple potential mechanisms of action combining cytotoxic, targeted, and immunological effects. This article takes an in-depth look at the role of trabectedin in the management of metastatic STS, including L-sarcoma and non-L-sarcoma.

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Efficacy of trabectedin in advanced soft tissue sarcoma: beyond lipo- and leiomyosarcoma

Cited by 37 publications

References 23 publications

Myxofibrosarcoma primary cultures: molecular and pharmacological profile

Myxofibrosarcoma primary cultures: molecular and pharmacological profile

Efficacy and safety of trabectedin for patients with unresectable and relapsed soft‐tissue sarcoma in Japan: A Japanese Musculoskeletal Oncology Group study

Update on the role of trabectedin in the treatment of intractable soft tissue sarcomas

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