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A Phase I Study of the Combination of Temsirolimus with Irinotecan for Metastatic Sarcoma
Department of Hematology/Oncology, The University of Vermont Cancer Center, 89 Beaumont Ave., Burlington, VT 05405, 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
Department of Orthopaedics, University of Texas Health Science Center San Antonio, San Antonio, TX 78229, USA
Department of Radiation Oncology, University of New Mexico Cancer Center, Albuquerque, NM 87131, USA
Department of Pathology, University of New Mexico Cancer Center, Albuquerque, NM 87131, USA
Division of Hematology/Oncology, University of New Mexico Cancer Center, Albuquerque, NM 87131, USA
* Author to whom correspondence should be addressed.
Received: 16 February 2013; in revised form: 25 March 2013 / Accepted: 6 April 2013 / Published: 11 April 2013
Abstract: 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.
Keywords: sarcoma; mTOR inhibitors; irinotecan; temsirolimus; phase I
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MDPI and ACS Style
Verschraegen, C.F.; Movva, S.; Ji, Y.; Schmit, B.; Quinn, R.H.; Liem, B.; Bocklage, T.; Shaheen, M. A Phase I Study of the Combination of Temsirolimus with Irinotecan for Metastatic Sarcoma. Cancers 2013, 5, 418-429.
Verschraegen CF, Movva S, Ji Y, Schmit B, Quinn RH, Liem B, Bocklage T, Shaheen M. A Phase I Study of the Combination of Temsirolimus with Irinotecan for Metastatic Sarcoma. Cancers. 2013; 5(2):418-429.
Verschraegen, Claire F.; Movva, Sujana; Ji, Yongli; Schmit, Berndt; Quinn, Robert H.; Liem, Ben; Bocklage, Therese; Shaheen, Monte. 2013. "A Phase I Study of the Combination of Temsirolimus with Irinotecan for Metastatic Sarcoma." Cancers 5, no. 2: 418-429.