RT Journal Article
T1 Assessment of Safety and Efficacy of Combined Trabectedin and Low-Dose Radiotherapy for Patients With Metastatic Soft-Tissue Sarcomas: A Nonrandomized Phase 1/2 Clinical Trial.
A1 Martin-Broto, Javier
A1 Hindi, Nadia
A1 Lopez-Pousa, Antonio
A1 Peinado-Serrano, Javier
A1 Alvarez, Rosa
A1 Alvarez-Gonzalez, Ana
A1 Italiano, Antoine
A1 Sargos, Paul
A1 Cruz-Jurado, Josefina
A1 Isern-Verdum, Josep
A1 Dolado, Maria Carmen
A1 Rincon-Perez, Inmaculada
A1 Sanchez-Bustos, Paloma
A1 Gutierrez, Antonio
A1 Romagosa, Cleofe
A1 Morosi, Carlo
A1 Grignani, Giovanni
A1 Gatti, Marco
A1 Luna, Pablo
A1 Alastuey, Ignacio
A1 Redondo, Andres
A1 Belinchon, Belen
A1 Martinez-Serra, Jordi
A1 Sunyach, Marie-Pierre
A1 Coindre, Jean-Michel
A1 Dei Tos, Angelo P
A1 Romero, Jesus
A1 Gronchi, Alessandro
A1 Blay, Jean-Yves
A1 Moura, David S
K1 Combined Modality Therapy
K1 Dose-Response Relationship, Radiation
K1 Humans
K1 Middle Aged
K1 Spain
K1 Trabectedin
AB Active therapeutic combinations, such as trabectedin and radiotherapy, offer potentially higher dimensional response in second-line treatment of advanced soft-tissue sarcomas. Dimensional response can be relevant both for symptom relief and for survival. To assess the combined use of trabectedin and radiotherapy in treating patients with progressing metastatic soft-tissue sarcomas. Phase 1 of this nonrandomized clinical trial followed the classic 3 + 3 design, with planned radiotherapy at a fixed dose of 30 Gy (3 Gy/d for 10 days) and infusion of trabectedin at 1.3 mg/m2 as the starting dose, 1.5 mg/m2 as dose level +1, and 1.1 mg/m2 as dose level -1. Phase 2 followed the Simon optimal 2-stage design. Allowing for type I and II errors of 10%, treatment success was defined as an overall response rate of 35%. This study was conducted in 9 sarcoma referral centers in Spain, France, and Italy from April 13, 2015, to November 20, 2018. Adult patients with progressing metastatic soft-tissue sarcoma and having undergone at least 1 previous line of systemic therapy were enrolled. In phase 2, patients fitting inclusion criteria and receiving at least 1 cycle of trabectedin and the radiotherapy regimen constituted the per-protocol population; those receiving at least 1 cycle of trabectedin, the safety population. Trabectedin was administered every 3 weeks in a 24-hour infusion. Radiotherapy was required to start within 1 hour after completion of the first trabectedin infusion (cycle 1, day 2). The dose-limiting toxic effects of trabectedin (phase 1) and the overall response rate (phase 2) with use of trabectedin plus irradiation in metastatic soft-tissue sarcomas. Eighteen patients (11 of whom were male) were enrolled in phase 1, and 27 other patients (14 of whom were female) were enrolled in phase 2. The median ages of those enrolled in phases 1 and 2 were 42 (range, 23-74) years and 51 (range, 27-73) years, respectively. In phase 1, dose-limiting toxic effects included grade 4 neutropenia lasting more than 5 days in 1 patient at the starting dose level and a grade 4 alanine aminotransferase level increase in 1 of 6 patients at the +1 dose level. In phase 2, among 25 patients with evaluable data, the overall response rate was 72% (95% CI, 53%-91%) for local assessment and 60% (95% CI, 39%-81%) for central assessment. The findings of this study suggest that the recommended dose of trabectedin for use in combination with this irradiation regimen is 1.5 mg/m2. The trial met its primary end point, with a high overall response rate that indicates the potential of this combination therapy for achieving substantial tumor shrinkage beyond first-line systemic therapy in patients with metastatic, progressing soft-tissue sarcomas. ClinicalTrials.gov Identifier: NCT02275286.
PB American Medical Association
YR 2020
FD 2020-02-20
LK http://hdl.handle.net/10668/15136
UL http://hdl.handle.net/10668/15136
LA en
NO Martin-Broto J, Hindi N, Lopez-Pousa A, Peinado-Serrano J, Alvarez R, Alvarez-Gonzalez A, et al. Assessment of Safety and Efficacy of Combined Trabectedin and Low-Dose Radiotherapy for Patients With Metastatic Soft-Tissue Sarcomas: A Nonrandomized Phase 1/2 Clinical Trial. JAMA Oncol. 2020 Apr 1;6(4):535-541. doi: 10.1001/jamaoncol.2019.6584. Erratum in: JAMA Oncol. 2020 Oct 1;6(10):1641.
DS RISalud
RD Apr 8, 2025