Trabectedin for metastatic soft tissue sarcoma: a retrospective single center analysis.
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.
Department of Internal Medicine V, Heidelberg University Clinics, Im Neuenheimer Feld 410, 69120 Heidelberg, Germany. Thomas.Schmitt@med.uni-heidelberg.de
Thomas
T
Schmitt
Eva
E
Keller
Sascha
S
Dietrich
Patrick
P
Wuchter
Anthony D
AD
Ho
Gerlinde
G
Egerer
D000293:Adolescent; D000328:Adult; D000368:Aged; D000818:Animals; D018906:Antineoplastic Agents, Alkylating / Q000009:adverse effects / Q000627:therapeutic use*; D004149:Dioxoles / Q000009:adverse effects / Q000627:therapeutic use*; D018450:Disease Progression; D018572:Disease-Free Survival; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D012509:Sarcoma / Q000188:drug therapy*; D044005:Tetrahydroisoquinolines / Q000009:adverse effects / Q000627:therapeutic use*; D000077606:Trabectedin; D014561:Urochordata; D055815:Young Adult
D018906:Antineoplastic Agents, Alkylating; D004149:Dioxoles; D044005:Tetrahydroisoquinolines; D000077606:Trabectedin