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- Title
Pharmacokinetics, safety, and activity of trabectedin as first-line treatment in elderly patients who are affected by advanced sarcoma and are unfit to receive standard chemotherapy: A phase 2 study (TR1US study) from the Italian Sarcoma Group.
- Authors
Grosso, Federica; D'Ambrosio, Lorenzo; Zucchetti, Massimo; Ibrahim, Toni; Tamberi, Stefano; Matteo, Cristina; Rulli, Eliana; Comandini, Danila; Palmerini, Emanuela; Baldi, Giacomo Giulio; DeCensi, Andrea; Bergaglio, Marina; Marra, Domenico; Marchesi, Emanuela; Siri, Giacomo; D'Incalci, Maurizio; Grignani, Giovanni
- Abstract
<bold>Background: </bold>Although elderly patients (≥70 years) represent 30% of new diagnoses of soft tissue sarcoma (STS), they are underrepresented in clinical trials and are often unfit to receive standard anthracycline-based chemotherapy. Trabectedin is registered as a second-line treatment for advanced STS and is characterized by a favorable safety profile.<bold>Methods: </bold>The aim of this single-arm, phase 2 study was to investigate trabectedin (scheduled dose, 1.3-1.5 mg/m2 ) as a first-line treatment in elderly patients with advanced stage STS who are inoperable and are unfit to receive standard anthracycline-based chemotherapy. The coprimary endpoints were progression-free survival at 3 months (PFS3) and the rate of clinically limiting toxicities (CLTs). We also conducted an ancillary study on pharmacokinetics.<bold>Results: </bold>Twenty-four patients (12 men and 12 women) with a median age of 79 years (interquartile range [IQR], 74-83 years) were enrolled. The histological subtype was leiomyosarcoma in 46%, liposarcoma in 33%, and other histotypes in 21%. The median number of trabectedin courses was 4 (IQR, 3-6), with 7 patients (29%) receiving ≥6 cycles. Eight patients (33%) required dose reductions. The most frequent grade 3/4 adverse events were neutropenia in 9 patients (38%), fatigue in 5 patients (21%), and aminotransferase elevation in 5 patients (21%). PFS3, median PFS, and overall survival were 71% (80% CI, 57%-81%), 4 months, and 12 months, respectively. Ten patients (42% [80% CI, 28%-57%]) experienced CLTs. Trabectedin Cmax , half-life, clearance, and distribution volume were 1.28 ng/mL (standard deviation [SD], 0.58 ng/mL), 26.70 hours (SD, 9.09 hours), 39.98 L/h/m2 (SD, 14.08 L/h/m2 ), and 1460 L/m2 (SD, 561 L/m2 ), respectively.<bold>Conclusion: </bold>Trabectedin can be administered safely to elderly patients with STS who are unfit to receive anthracyclines. Pharmacokinetics in the elderly population was superimposable to historical data.
- Subjects
ITALY; OLDER patients; LIPOSARCOMA; SARCOMA; PHARMACOKINETICS; CANCER chemotherapy; STANDARD deviations; THERAPEUTIC use of antineoplastic agents; RESEARCH; RESEARCH methodology; ANTINEOPLASTIC agents; MEDICAL cooperation; EVALUATION research; COMPARATIVE studies; RESEARCH funding
- Publication
Cancer (0008543X), 2020, Vol 126, Issue 21, p4726
- ISSN
0008-543X
- Publication type
journal article
- DOI
10.1002/cncr.33120