Javier Martin-Broto1, Antonio López Pousa2, Ramón de Las Peñas2, Xavier García Del Muro2, Antonio Gutierrez2, Javier Martinez-Trufero2, Josefina Cruz2, Rosa Alvarez2, Ricardo Cubedo2, Andrés Redondo2, Joan Maurel2, Juan A Carrasco2, José A López-Martin2, Ángeles Sala2, José Andrés Meana2, Rafael Ramos2, Jordi Martinez-Serra2, José A Lopez-Guerrero2, Isabel Sevilla2, Carmen Balaña2, Ángeles Vaz2, Ana De Juan2, Regina Alemany2, Andrés Poveda2. 1. Javier Martin-Broto, Virgen del Rocio Hospital and Biomedicine Institute, Sevilla; Antonio López Pousa, Sant Pau Hospital; Xavier García del Muro, Institut Català d'Oncologia; and Joan Maurel, CIBERehd, IDIBAPS, Hospital Clinic, Barcelona; Ramón de las Peñas, Provincial Hospital, Castellón; Antonio Gutierrez, Rafael Ramos, and Jordi Martinez-Serra, Son Espases Hospital; and Regina Alemany, Balearic Islands University, Palma de Mallorca; Javier Martinez-Trufero, Miguel Servet Hospital, Zaragoza; Josefina Cruz, University Hospital Canarias, Tenerife; Rosa Alvarez, Gregorio Marañón Hospital; Ricardo Cubedo, Puerta de Hierro Hospital; Andrés Redondo, La Paz University Hospital; José A. López-Martin, 12 de Octubre Hospital; and Ángeles Vaz, Ramón y Cajal Hospital, Madrid; Juan A. Carrasco, Xeral Cies Hospital, Vigo; Ángeles Sala and Ana De Juan, Basurto Hospital, Bilbao; José Andrés Meana, University General Hospital, Alicante; José A. Lopez-Guerrero and Andrés Poveda, Valencian Oncologic Institute, Valencia; Isabel Sevilla, Virgen de la Victoria Hospital, Málaga; and Carmen Balaña, Insitut Català d'Oncologia, Badalona, Spain. jmartin@mustbesevilla.org. 2. Javier Martin-Broto, Virgen del Rocio Hospital and Biomedicine Institute, Sevilla; Antonio López Pousa, Sant Pau Hospital; Xavier García del Muro, Institut Català d'Oncologia; and Joan Maurel, CIBERehd, IDIBAPS, Hospital Clinic, Barcelona; Ramón de las Peñas, Provincial Hospital, Castellón; Antonio Gutierrez, Rafael Ramos, and Jordi Martinez-Serra, Son Espases Hospital; and Regina Alemany, Balearic Islands University, Palma de Mallorca; Javier Martinez-Trufero, Miguel Servet Hospital, Zaragoza; Josefina Cruz, University Hospital Canarias, Tenerife; Rosa Alvarez, Gregorio Marañón Hospital; Ricardo Cubedo, Puerta de Hierro Hospital; Andrés Redondo, La Paz University Hospital; José A. López-Martin, 12 de Octubre Hospital; and Ángeles Vaz, Ramón y Cajal Hospital, Madrid; Juan A. Carrasco, Xeral Cies Hospital, Vigo; Ángeles Sala and Ana De Juan, Basurto Hospital, Bilbao; José Andrés Meana, University General Hospital, Alicante; José A. Lopez-Guerrero and Andrés Poveda, Valencian Oncologic Institute, Valencia; Isabel Sevilla, Virgen de la Victoria Hospital, Málaga; and Carmen Balaña, Insitut Català d'Oncologia, Badalona, Spain.
Abstract
PURPOSE:Doxorubicin and trabectedin are considered active drugs in soft tissue sarcoma (STS). The combination of both drugs was hypothesized to be advantageous and safe on the basis of preclinical evidence and a previous phase I trial, respectively. The aim of this study was to compare the clinical outcome of trabectedin plus doxorubicin with doxorubicin as first-line treatment of advanced STS patients. PATIENTS AND METHODS: In this open-label randomized phase II trial, the main end point was progression-free survival (PFS). Trabectedin 1.1 mg/m(2) in a 3-hour infusion plus doxorubicin 60 mg/m(2) as the experimental arm and doxorubicin 75 mg/m(2) as the control arm were administered for up to six cycles. Translational research was planned to correlate the expression of apoptotic and DNA repair genes with clinical outcome. RESULTS: In 115 randomly assigned patients, the median PFS was 5.5 months in the control arm and 5.7 months in the experimental arm (hazard ratio, 1.16; 95% CI, 0.79 to 1.71; P = .45) in the intent-to-treat analysis. The trial was stopped for futility after the interim analysis, because the results in the experimental arm showed the risk reduction for the main end point to be < 9.64%. The proportion of patients with grade 3 or 4 thrombocytopenia, asthenia, and liver toxicity was significantly higher in the experimental arm. FAS and p53 were shown to be prognostic factors for PFS (7.0 months if FAS+ and p53-; 3.4 months if FAS+/p53+ or FAS-/p53-; and 0.7 months if FAS- and p53+; P < .001) and for overall survival. CONCLUSION:Trabectedin plus doxorubicin did not show superiority over doxorubicin alone as first-line treatment of advanced STS. The prognostic role of apoptotic key genes, FAS and p53, was shown to be robust enough to continue this research line.
RCT Entities:
PURPOSE:Doxorubicin and trabectedin are considered active drugs in soft tissue sarcoma (STS). The combination of both drugs was hypothesized to be advantageous and safe on the basis of preclinical evidence and a previous phase I trial, respectively. The aim of this study was to compare the clinical outcome of trabectedin plus doxorubicin with doxorubicin as first-line treatment of advanced STS patients. PATIENTS AND METHODS: In this open-label randomized phase II trial, the main end point was progression-free survival (PFS). Trabectedin 1.1 mg/m(2) in a 3-hour infusion plus doxorubicin 60 mg/m(2) as the experimental arm and doxorubicin 75 mg/m(2) as the control arm were administered for up to six cycles. Translational research was planned to correlate the expression of apoptotic and DNA repair genes with clinical outcome. RESULTS: In 115 randomly assigned patients, the median PFS was 5.5 months in the control arm and 5.7 months in the experimental arm (hazard ratio, 1.16; 95% CI, 0.79 to 1.71; P = .45) in the intent-to-treat analysis. The trial was stopped for futility after the interim analysis, because the results in the experimental arm showed the risk reduction for the main end point to be < 9.64%. The proportion of patients with grade 3 or 4 thrombocytopenia, asthenia, and liver toxicity was significantly higher in the experimental arm. FAS and p53 were shown to be prognostic factors for PFS (7.0 months if FAS+ and p53-; 3.4 months if FAS+/p53+ or FAS-/p53-; and 0.7 months if FAS- and p53+; P < .001) and for overall survival. CONCLUSION:Trabectedin plus doxorubicin did not show superiority over doxorubicin alone as first-line treatment of advanced STS. The prognostic role of apoptotic key genes, FAS and p53, was shown to be robust enough to continue this research line.
Authors: Rebecca C Arend; Michael D Toboni; Allison M Montgomery; Robert A Burger; Alexander B Olawaiye; Bradley J Monk; Thomas J Herzog Journal: Oncologist Date: 2018-08-23
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Authors: John E Mullinax; MacLean Hall; Matthew Beatty; Amy M Weber; Zachary Sannasardo; Tanja Svrdlin; Jonathan Hensel; Marilyn Bui; Allison Richards; Ricardo J Gonzalez; Cheryl A Cox; Linda Kelley; James J Mulé; Amod A Sarnaik; Shari Pilon-Thomas Journal: J Immunother Date: 2021 Feb-Mar 01 Impact factor: 4.912