Trabectedin for Advanced Soft Tissue Sarcomas: A Single Institution Experience

Gounaris, Ioannis; Hatcher, Helen; Davidson, Dochka; Sherbourne, Karen; Alam, Salma; Zaki, Kamarul; Horan, Gail; Earl, Helena

doi:10.2217/fon.14.10

Cited by 14 publications

(6 citation statements)

References 25 publications

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“…Dose reductions and delays occurred more frequently in the trabectedin group than in the dacarbazine group, but were protocol-specified with the intent of minimizing trabectedin-related toxicity. These dosage adjustments were similar to those reported in other trabectedin studies, and were primarily due to transaminase elevations, neutropenia, or anemia [17, 22, 25]. The improved disease control, with equivalent reported QOL reported in the total ET43-SAR-3007 study population, suggests the importance of proper dose adjustment in patients receiving trabectedin, the majority of whom were treated as outpatients in the current study.…”

Section: Discussionsupporting

confidence: 84%

Efficacy and safety of trabectedin or dacarbazine in patients with advanced uterine leiomyosarcoma after failure of anthracycline-based chemotherapy: Subgroup analysis of a phase 3, randomized clinical trial

Hensley

Patel

Mehren

et al. 2017

Gynecologic Oncology

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Objective Trabectedin demonstrated significantly improved disease control in leiomyosarcoma and liposarcoma patients in a global phase 3 trial (NCT01343277). A post hoc analysis was conducted to assess the efficacy and safety of trabectedin or dacarbazine in women with uterine leiomyosarcoma (uLMS), the largest subgroup of enrolled patients (40%). Methods Of 577 patients randomized 2:1 to receive trabectedin 1.5 mg/m2 by 24-hour IV infusion or dacarbazine 1 g/m2 by 20–120-minute IV infusion once every three weeks, 232 had uLMS (trabectedin: 144; dacarbazine: 88). The primary endpoint was overall survival (OS); secondary endpoints were progression-free survival (PFS), objective response rate (ORR), clinical benefit rate (CBR: complete responses + partial responses + stable disease [SD] for at least 18 weeks), duration of response (DOR), and safety. Results PFS for trabectedin was 4.0 months compared with 1.5 months for dacarbazine (hazard ratio [HR]=0.57; 95% CI 0.41–0.81; P=.0012). OS was similar (trabectedin 13.4 months vs. dacarbazine 12.9 months, HR=0.89; 95% CI 0.65–1.24; P=.51) between groups. ORR was 11% with trabectedin vs. 9% with dacarbazine (P=.82). CBR for trabectedin was 31% vs. 18% with dacarbazine (P=.05); median DOR was 6.5 months for trabectedin vs. 4.1 months for dacarbazine (P=.32). Grade 3/4 treatment-emergent adverse events observed in ≥10% of patients in the trabectedin group included transient aminotransferase (aspartate/alanine) elevations, anemia, leukopenia, and thrombocytopenia. Conclusions In this post hoc subset analysis of patients with uLMS who had received prior anthracycline therapy, trabectedin treatment resulted in significantly longer PFS versus dacarbazine, with an acceptable safety profile. There was no difference in OS.

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Section: Discussionsupporting

confidence: 84%

Efficacy and safety of trabectedin or dacarbazine in patients with advanced uterine leiomyosarcoma after failure of anthracycline-based chemotherapy: Subgroup analysis of a phase 3, randomized clinical trial

Hensley

Patel

Mehren

et al. 2017

Gynecologic Oncology

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“…Dosage and scheduling adjustments were in concordance with those reported by other studies. Dose reduction was necessary in 19.5 % of patients, which is well within the rate reported in the literature (14–48 %) [ 13 , 17 , 24 , 26 ]. As expected the primarily causes for dose reduction were either low ANC or elevated liver enzymes [ 13 , 26 ].…”

Section: Discussionsupporting

confidence: 82%

“…Trabectedin treatment in our cohort was reasonably well tolerated with an overall safety profile consistent with that of previous studies. As previously reported, the most common toxicities included self-limiting low ANC and elevated liver enzymes [ 25 , 26 ]. Neutropenia was the most common drug-related toxicity and its incidence and severity is particularly higher with the dosing schedule used by our group [ 25 ].…”

Section: Discussionmentioning

confidence: 73%

Trabectedin for inoperable or recurrent soft tissue sarcoma in adult patients: a retrospective cohort study

et al. 2016

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BackgroundTrabectedin is an antineoplastic agent used for patients with soft tissue sarcoma (STS) who fail standard-of-care treatment. Real-world data of its performance is scarce. This study evaluates the safety and effectiveness of trabectedin for patients with advanced STS who were treated at a high-volume sarcoma center.MethodsA retrospective chart review was performed on 77 patients treated with trabectedin (24 h infusion q3w) between 01/2005 and 05/2014. Data regarding safety, objective radiological response, progression-free and overall survival were analyzed.ResultsMedian age at treatment onset was 52y [interquartile range (IQR): 45-61y]. Tumors included leiomyosarcoma (41.6 %), liposarcoma (18.2 %), and synovial sarcoma (13 %). Trabectedin was provided as ≥ third-line chemotherapy in 71.4 %. Median number of cycles was 2 (range: 1–17). Dose reduction and treatment delays occurred in 19.5 and 40.3 %, respectively. Toxicities occurred in 78 %, primarily for neutropenia or elevated liver enzymes. Two patients died secondary to trabectedin-induced rhabdomyolysis. Treatment was discontinued because of disease progression (84.7 %), toxicity (10 %), and patient preference (5 %). Partial response or stable disease occurred in 14.1 and 33.8 %, respectively, while 52.1 % developed progressive disease. Median progression-free survival was 1.3 m (IQR: 0.7–3.5 m) and was significantly higher in patients lacking severe toxicities or progressive disease. Median overall survival was 6.7 m (IQR: 2.3–12.7 m) and was significantly higher in patients with leiomyosarcoma or liposarcoma relative to other histologies.ConclusionsTrabectedin has an acceptable safety profile as an anti-tumor agent. Our data further suggest there may be some benefit in using trabectedin particularly in patients with leiomyo- or liposarcoma who failed standard-of-care agents.

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“…It should be noted that the positive results from this pivotal trial were the main reason for trabectedin approval in the United States by the US Food and Drug Administration (FDA) and in other parts of the world. Additionally, considering retrospective studies published until this time, trabectedin showed interesting efficacy in routine clinical practice . Moreover, from a medico‐economic point of view, trabectedin was found to be cost‐effective as an orphan drug for patients with short life expectancy .…”

Section: Targeting the Tumor Vasculature By Natural Compounds: Perspementioning

confidence: 99%

Starvation tactics using natural compounds for advanced cancers: pharmacodynamics, clinical efficacy, and predictive biomarkers

2018

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The high mortality associated with oncological diseases is mostly due to tumors in advanced stages, and their management is a major challenge in modern oncology. Angiogenesis is a defined hallmark of cancer and predisposes to metastatic invasion and dissemination and is therefore an important druggable target for cancer drug discovery. Recently, because of drug resistance and poor prognosis, new anticancer drugs from natural sources targeting tumor vessels have attracted more attention and have been used in several randomized and controlled clinical trials as therapeutic options. Here, we outline and discuss potential natural compounds as salvage treatment for advanced cancers from recent and ongoing clinical trials and real‐world studies. We also discuss predictive biomarkers for patients' selection to optimize the use of these potential anticancer drugs.

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Trabectedin for Advanced Soft Tissue Sarcomas: A Single Institution Experience

Abstract: Treatment with trabectedin is effective and well tolerated in heavily pretreated soft tissue sarcoma patients. Tapering dexamethasone courses and switching trabectedin administration to an every 4 weeks schedule effectively dealt with persistent fatigue without compromising effectiveness.

Cited by 14 publications

References 25 publications

Efficacy and safety of trabectedin or dacarbazine in patients with advanced uterine leiomyosarcoma after failure of anthracycline-based chemotherapy: Subgroup analysis of a phase 3, randomized clinical trial

Efficacy and safety of trabectedin or dacarbazine in patients with advanced uterine leiomyosarcoma after failure of anthracycline-based chemotherapy: Subgroup analysis of a phase 3, randomized clinical trial

Trabectedin for inoperable or recurrent soft tissue sarcoma in adult patients: a retrospective cohort study

Starvation tactics using natural compounds for advanced cancers: pharmacodynamics, clinical efficacy, and predictive biomarkers

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