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Trabectedin for metastatic soft tissue sarcoma: a retrospective single center analysis.

Schmitt T, Keller E, Dietrich S, Wuchter P, Ho AD, Egerer G - Mar Drugs (2010)

Bottom Line: Side effects, including neutropenia, elevation of liver transaminases/liver function tests, and nausea/vomiting, were usually mild and manageable.However, dose reductions due to side effects were necessary in five patients.We conclude that trabectedin is an effective and generally well tolerated treatment for STS even in a heavily pre-treated patient population.

View Article: PubMed Central - PubMed

Affiliation: Department of Internal Medicine V, Heidelberg University Clinics, Im Neuenheimer Feld 410, 69120 Heidelberg, Germany. Thomas.Schmitt@med.uni-heidelberg.de

ABSTRACT
Soft tissue sarcoma (STS) comprises a large variety of rare malignant tumors. Development of distant metastasis is frequent, even in patients undergoing initial curative surgery. Trabectedin, a tetrahydroisoquinoline alkaloid isolated from the Caribbean marine tunicate Ecteinascidia turbinata, was approved in 2007 for patients with advanced STS after failure of anthracyclines and ifosfamide, or for patients unsuited to receive these agents. In this study, we retrospectively analyzed 25 patients who had been treated with trabectedin at our institution between 2007 and 2010. The majority (72%) had been heavily pre-treated with ≥2 previous lines of chemotherapy. Response assessed by conventional RECIST criteria was low, with only one patient achieving a partial remission (PR) and 10 stable disease (SD) after three cycles of treatment. However, median progression-free survival (PFS) and overall survival (OS) were significantly prolonged in this population compared to non-responders, with 7.7 months versus 2.1 months (p < 0.0001; HR 15.37, 95% CI 4.3 to 54.5) and 12.13 months versus 5.54 months (p = 0.0137; HR 3.7, 95% CI 1.3 to 10.5), respectively. PFS for all patients was 58% at three months and 37% at six months. Side effects, including neutropenia, elevation of liver transaminases/liver function tests, and nausea/vomiting, were usually mild and manageable. However, dose reductions due to side effects were necessary in five patients. We conclude that trabectedin is an effective and generally well tolerated treatment for STS even in a heavily pre-treated patient population.

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Progression-free survival for all patients. Progression-free survival (months) from start of trabectedin to disease progression was estimated using the method of Kaplan and Meier.
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f1-marinedrugs-08-02647: Progression-free survival for all patients. Progression-free survival (months) from start of trabectedin to disease progression was estimated using the method of Kaplan and Meier.

Mentions: Best response by RECIST criteria after three cycles of treatment were PR (n = 1) and SD (n = 10). Primarily progressive disease was seen in 14 patients. Two patients (Pat. 017 and UPN 018) discontinued treatment after six and 12 cycles of therapy achieving SD. Median PFS and OS for the whole population were 3.7 and 8.8 months, respectively. PFS at three and six months was 58% and 37% (Figures 1 and 2). However, patients responding to therapy (defined as PR or SD after three cycles of treatment with trabectedin) had a significantly longer median PFS and OS with 7.7 months versus 2.1 months (p < 0.0001; HR 15.37, 95% CI 4.3 to 54.5) and 12.13 months versus 5.54 months (p = 0.0137; HR 3.7, 95% CI 1.3 to 10.5) (Figure 3 and 4). In general, response assessment by different histological subsets was not possible due to small patient numbers. However, comparing patients with leiomyosarcoma versus other histological subtypes, we found a significant difference in median OS (10.8 vs. 7.8 months; p = 0.01; HR 4.5, 95% CI 1.4 to 14.4) but not in PFS (3.7 vs. 2.9 months;


Trabectedin for metastatic soft tissue sarcoma: a retrospective single center analysis.

Schmitt T, Keller E, Dietrich S, Wuchter P, Ho AD, Egerer G - Mar Drugs (2010)

Progression-free survival for all patients. Progression-free survival (months) from start of trabectedin to disease progression was estimated using the method of Kaplan and Meier.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC2992998&req=5

f1-marinedrugs-08-02647: Progression-free survival for all patients. Progression-free survival (months) from start of trabectedin to disease progression was estimated using the method of Kaplan and Meier.
Mentions: Best response by RECIST criteria after three cycles of treatment were PR (n = 1) and SD (n = 10). Primarily progressive disease was seen in 14 patients. Two patients (Pat. 017 and UPN 018) discontinued treatment after six and 12 cycles of therapy achieving SD. Median PFS and OS for the whole population were 3.7 and 8.8 months, respectively. PFS at three and six months was 58% and 37% (Figures 1 and 2). However, patients responding to therapy (defined as PR or SD after three cycles of treatment with trabectedin) had a significantly longer median PFS and OS with 7.7 months versus 2.1 months (p < 0.0001; HR 15.37, 95% CI 4.3 to 54.5) and 12.13 months versus 5.54 months (p = 0.0137; HR 3.7, 95% CI 1.3 to 10.5) (Figure 3 and 4). In general, response assessment by different histological subsets was not possible due to small patient numbers. However, comparing patients with leiomyosarcoma versus other histological subtypes, we found a significant difference in median OS (10.8 vs. 7.8 months; p = 0.01; HR 4.5, 95% CI 1.4 to 14.4) but not in PFS (3.7 vs. 2.9 months;

Bottom Line: Side effects, including neutropenia, elevation of liver transaminases/liver function tests, and nausea/vomiting, were usually mild and manageable.However, dose reductions due to side effects were necessary in five patients.We conclude that trabectedin is an effective and generally well tolerated treatment for STS even in a heavily pre-treated patient population.

View Article: PubMed Central - PubMed

Affiliation: Department of Internal Medicine V, Heidelberg University Clinics, Im Neuenheimer Feld 410, 69120 Heidelberg, Germany. Thomas.Schmitt@med.uni-heidelberg.de

ABSTRACT
Soft tissue sarcoma (STS) comprises a large variety of rare malignant tumors. Development of distant metastasis is frequent, even in patients undergoing initial curative surgery. Trabectedin, a tetrahydroisoquinoline alkaloid isolated from the Caribbean marine tunicate Ecteinascidia turbinata, was approved in 2007 for patients with advanced STS after failure of anthracyclines and ifosfamide, or for patients unsuited to receive these agents. In this study, we retrospectively analyzed 25 patients who had been treated with trabectedin at our institution between 2007 and 2010. The majority (72%) had been heavily pre-treated with ≥2 previous lines of chemotherapy. Response assessed by conventional RECIST criteria was low, with only one patient achieving a partial remission (PR) and 10 stable disease (SD) after three cycles of treatment. However, median progression-free survival (PFS) and overall survival (OS) were significantly prolonged in this population compared to non-responders, with 7.7 months versus 2.1 months (p < 0.0001; HR 15.37, 95% CI 4.3 to 54.5) and 12.13 months versus 5.54 months (p = 0.0137; HR 3.7, 95% CI 1.3 to 10.5), respectively. PFS for all patients was 58% at three months and 37% at six months. Side effects, including neutropenia, elevation of liver transaminases/liver function tests, and nausea/vomiting, were usually mild and manageable. However, dose reductions due to side effects were necessary in five patients. We conclude that trabectedin is an effective and generally well tolerated treatment for STS even in a heavily pre-treated patient population.

Show MeSH
Related in: MedlinePlus