title: Trabectedin in metastatic soft tissue sarcomas: Role of pretreatment and age.
abstract: Trabectedin has mostly been studied in metastatic leiomyosarcoma and liposarcomas. Only limited data are available in other sarcoma subtypes, heavily pretreated and elderly patients. We retrospectively analyzed 101 consecutive sarcoma patients treated with trabectedin at our center. We recorded progression-free survival (PFS), clinical benefit rate (CBR, defined as complete or partial response or stable disease for at least 6 weeks) and toxicity. Covariates were sarcoma subtype, age and pretreatment. On average, trabectedin was administered for 2nd relapse/progression (range 1st to 12th line). A median of 2 cycles and a dose of 1.5 mg/m2 (range 1-21 cycles; 1.3-1.5 mg/m2) was administered. The median PFS under treatment with trabectedin was 2.1 months in the overall population. Different clinical outcomes were observed with respect to sarcoma subtypes: in patients with L-sarcoma [defined as leiosarcoma and liposarcoma (n=25)] the CBR was 55%. Notably, long lasting remissions were even observed in 7th-line treatment. In contrast, the majority of patients with non-L-sarcomas quickly progressed (median PFS 1.6 months). Nevertheless, a CBR of 34% was achieved, including long-lasting disease stabilization in subtypes such as rhabdomyosarcoma. Patients treated with trabectedin at 1st or 2nd line (n=16) achieved an improved PFS (median 5.7 months, range) and a CBR of 59%. No differences in terms of toxicity or efficacy were observed between patients older than 65 years (n=23) and younger patients (n=78). In this non-trial setting, port-associated complications were more frequent (14%) with trabectedin compared to other continuous infusion protocols administered at our outpatient therapy center. The majority of patients with relapsing L-sarcomas and a substantial fraction of patients with non-L-sarcomas derive a clinically meaningful benefit from trabectedin. Outpatient treatment is well tolerated also in elderly and heavily pretreated patients. Port-associated complications were observed at an unusually high rate. This suggests a drug-specific local toxicity that merits further investigation.
authors: Sarcoma Center, Departments of Medical Oncology, Surgical Oncology and Pathology, West German Cancer Center, University Hospital Essen, University Duisburg-Essen, D-45122 Essen, Germany.
authors: Mathias
authors: M
authors: Hoiczyk
authors: Florian
authors: F
authors: Grabellus
authors: Lars
authors: L
authors: Podleska
authors: Marit
authors: M
authors: Ahrens
authors: Benjamin
authors: B
authors: Schwindenhammer
authors: Georg
authors: G
authors: Taeger
authors: Christoph
authors: C
authors: Pöttgen
authors: Martin
authors: M
authors: Schuler
authors: Sebastian
authors: S
authors: Bauer
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D004149:Dioxoles / Q000008:administration & dosage* / Q000009:adverse effects; D018450:Disease Progression; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007890:Leiomyosarcoma / Q000188:drug therapy* / Q000473:pathology; D008080:Liposarcoma / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis / Q000188:drug therapy; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy / Q000473:pathology; D012509:Sarcoma / Q000188:drug therapy* / Q000473:pathology; D044005:Tetrahydroisoquinolines / Q000008:administration & dosage* / Q000009:adverse effects; D000077606:Trabectedin
chemical_list: D004149:Dioxoles; D044005:Tetrahydroisoquinolines; D000077606:Trabectedin
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