Pemetrexed plus cisplatin in patients with previously treated advanced sarcoma: a multicenter, single-arm, phase II trial

ESMO Open

article

J.H. Kim¹  S.H. Kim²  M.K. Jeon³  J.E. Kim⁴  K.H. Kim⁵  K.-H. Yun³  H.-C. Jeung¹  S.Y. Rha³  J.-H. Ahn⁴  H.S. Kim³ 

[1] Division of Medical Oncology, Department of Internal Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine;Pathology Center, Seegene Medical Foundation;Division of Medical Oncology, Department of Internal Medicine, Yonsei Cancer Center, Yonsei University College of Medicine;Department of Oncology, University of Ulsan College of Medicine, Asan Medical Center;Division of Medical Oncology, Department of Internal Medicine, Inje University College of Medicine, Busan Paik Hospital;Brain Korea 21 PLUS Project for Medical Sciences, Yonsei University College of Medicine;Songdang Institute for Cancer Research, Yonsei University College of Medicine

关键词: soft tissue sarcoma;    bone sarcoma;    pemetrexed;    cisplatin;    thymidylate synthase;    excision repair cross-complementation group 1;   

DOI  :  10.1016/j.esmoop.2021.100249

学科分类：社会科学、人文和艺术（综合）

来源: BMJ Publishing Group

【 摘 要 】

Background Patients with advanced sarcomas have a poor prognosis and few treatment options that improve overall survival. We assessed the efficacy and tolerability of pemetrexed and cisplatin combination therapy in patients with refractory bone and soft tissue sarcoma (STS).Patients and Methods Patients were included in this multicenter, phase II study (ClinicalTrials.gov identifier NCT03809637) if they progressed after receiving one or more chemotherapy regimens containing an anthracycline and/or ifosfamide. Pemetrexed was first administered intravenously, followed by cisplatin, over a cycle of 21 days, for a maximum of six cycles. The primary endpoint was a progression-free rate (PFR) at 3 months (3-month PFR).Results From January 2017 to September 2019, we enrolled 37 patients; of these, 73% had previously undergone three or more rounds of chemotherapy. Five patients (13.5%) exhibited objective responses, including two patients (2/6, 33.3%) with malignant peripheral nerve sheath tumors, one patient (1/4, 25%) with synovial sarcoma, one patient (1/4, 25%) with undifferentiated pleomorphic sarcoma, and one patient (1/4, 25%) with angiosarcoma. The median progression-free survival was 2.6 months, and the 3-month PFR was 45.9% (n = 17). None of the four patients with osteosarcoma exhibited objective responses or were progression free at 3 months. The most frequent treatment-related grade 3-4 toxicities included neutropenia (16.2%), anemia (13.5%), thrombocytopenia (13.5%), and fatigue (8.1%). Among 26 patients (70.3%) available for immunohistochemical assessments, patients in the low-excision repair cross-complementation group 1 (ERCC1) and low-thymidylate synthase expression groups showed a tendency for longer overall survival.Conclusions Combination therapy with pemetrexed and cisplatin was associated with clinically meaningful and sustained responses among patients with advanced and refractory STS. The combination therapy met its predefined primary study endpoint.

【 授权许可】

CC BY|CC BY-NC-ND