Antitumor activity of lurbinectedin in combination with oral capecitabine in patients with metastatic breast cancer
| Autor: | A.H. Awada, V. Boni, V. Moreno, P. Aftimos, C. Kahatt, X.E. Luepke-Estefan, M. Siguero, C. Fernandez-Teruel, M. Cullell-Young, J. Tabernero |
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| Přispěvatelé: | Institut Català de la Salut, [Awada AH, Aftimos P] Oncology Medicine Department, Institut Jules Bordet, Université Libre de Bruxelles, Brussels, Belgium. [Boni V] START Madrid—HM CIOCC, Hospital Madrid Norte Sanchinarro, Madrid, Spain. [Moreno V] START Madrid—FJD, Hospital Universitario Fundación Jiménez Díaz, Madrid, Spain. [Kahatt C, Luepke-Estefan XE] PharmaMar, Colmenar Viejo, Madrid, Spain. [Tabernero J] Vall d’Hebron Hospital Universitari, Barcelona, Spain. Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain. IOB-Quirón, UVic-UCC, Barcelona, Spain, Vall d'Hebron Barcelona Hospital Campus |
| Rok vydání: | 2022 |
| Předmět: |
neoplasias::neoplasias por localización::neoplasias de la mama [ENFERMEDADES]
Cancer Research Metàstasi Oncology neoplasias::procesos neoplásicos::metástasis neoplásica [ENFERMEDADES] Neoplasms::Neoplasms by Site::Breast Neoplasms [DISEASES] Therapeutics::Therapeutics::Drug Therapy::Antineoplastic Protocols::Therapeutics::Drug Therapy::Antineoplastic Combined Chemotherapy Protocols [ANALYTICAL DIAGNOSTIC AND THERAPEUTIC TECHNIQUES AND EQUIPMENT] Mama - Càncer - Tractament Neoplasms::Neoplastic Processes::Neoplasm Metastasis [DISEASES] terapéutica::terapéutica::farmacoterapia::protocolos antineoplásicos::terapéutica::farmacoterapia::protocolos de quimioterapia antineoplásica combinada [TÉCNICAS Y EQUIPOS ANALÍTICOS DIAGNÓSTICOS Y TERAPÉUTICOS] Otros calificadores::Otros calificadores::/farmacoterapia [Otros calificadores] Other subheadings::Other subheadings::/drug therapy [Other subheadings] Quimioteràpia combinada |
| Zdroj: | Scientia |
| ISSN: | 2059-7029 |
| Popis: | Breast cancer; Capecitabine; Lurbinectedin Cáncer de mama; Capecitabina; Lurbinectedina Càncer de mama; Capecitabina; Lurbinectedina Background Preclinical studies showed a synergistic effect for 5-fluorouracil and lurbinectedin against solid tumors. This phase I trial evaluated a combination of capecitabine plus lurbinectedin in patients with selected advanced solid tumors. Results in patients with relapsed metastatic breast cancer (MBC) are described. Patients and methods Patients received capecitabine daily on day (D)1-D14 combined with lurbinectedin on D1, D8 or D1 every 3 weeks (q3w) intravenously, following a standard 3 + 3 escalation design and expansion at the recommended dose (RD). Results Of the 81 enrolled patients, 28 had relapsed MBC: 20 with hormone receptor (HR)-positive tumors and 8 with triple-negative tumors; 3 treated in the D1,D8 schedule and 25 in the D1 schedule. The RD was capecitabine 1650 mg/m2 daily on D1-D14 plus lurbinectedin 2.2 mg/m2 on D1 q3w. Sixteen confirmed responses and two prolonged disease stabilizations (≥6 months) were observed [overall response rate (ORR)/clinical benefit rate (CBR) = 57%/64% at all dose levels; 47%/60% at the RD]. Twelve responses and both prolonged stabilizations occurred in HR-positive tumors (ORR/CBR = 60%/70% at all dose levels, 56%/78% at the RD). Four responses were found in triple-negative tumors (ORR and CBR = 50% at all dose levels; 33% at the RD). Myelotoxicity was reversible and manageable at the RD; most non-hematological toxicities were mild/moderate. No episodes of febrile neutropenia or severe palmar-plantar erythrodysesthesia syndrome occurred. No major pharmacokinetic drug–drug interaction was found between lurbinectedin, capecitabine or capecitabine metabolites. Conclusions The capecitabine/lurbinectedin combination showed encouraging clinical activity in relapsed MBC, especially in HR-positive tumors. Toxicity was manageable at the RD. Further development is warranted in relapsed MBC. This work was supported by Pharma Mar S.A., including grants from the Centro para el Desarrollo Tecnológico Industrial (CDTI) during the conduct of the study [grant number IDI-20130013]. |
| Databáze: | OpenAIRE |
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