A Phase I Study of the Combination of Temsirolimus with Irinotecan for Metastatic Sarcoma

Cancers

Claire F. Verschraegen³  Sujana Movva⁵  Yongli Ji³  Berndt Schmit⁶  Robert H. Quinn⁴  Ben Liem²  Therese Bocklage¹ 

[1] Department of Pathology, University of New Mexico Cancer Center, Albuquerque, NM 87131, USA;Department of Radiation Oncology, University of New Mexico Cancer Center, Albuquerque, NM 87131, USA;Department of Hematology/Oncology, The University of Vermont Cancer Center, 89 Beaumont Ave., Burlington, VT 05405, USA;Department of Orthopaedics, University of Texas Health Science Center San Antonio, San Antonio, TX 78229, USA;Department of Medical Oncology, Fox Chase Cancer Center, Pennsylvania, PA 19111, USA;Department of Radiology, University of Pittsburgh Medical Center East, Pittsburgh, PA 15146, USA

关键词: sarcoma;    mTOR inhibitors;    irinotecan;    temsirolimus;    phase I;   

DOI  :  10.3390/cancers5020418

来源: mdpi

【 摘 要 】

mTOR inhibitors are emerging as important anti-neoplastic agents with a wide range of clinical applications. The topoisomerase I inhibitor irinotecan is a potent DNA damaging drug, with a broad spectrum of anticancer activities. mTOR appears to enhance cancer cell survival following DNA damage, thus the inhibition of mTOR after irinotecan could theoretically show synergistic activities in patients. Both mTOR inhibitors and irinotecan have been used as single agents in soft tissue sarcomas with limited efficacy. We completed a phase I trial of the combination of the mTOR inhibitor, temsirolimus, and irinotecan in patients with advanced soft tissue sarcoma. Seventeen patients were recruited. The Phase II recommended dose is 20 mg of temsirolimus and 80 mg/m² of irinotecan administered on weekly basis for three out of four weeks. Most frequently encountered toxicities include cytopenias, fatigue, and gastrointestinal toxicities. Two patients (one with leiomyosarcoma and one with high grade undifferentiated sarcoma) had stable disease for more than 12 months.

【 授权许可】

CC BY   
© 2013 by the authors; licensee MDPI, Basel, Switzerland.