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A phase II study of tasisulam sodium (LY573636 sodium) as second-line or third-line treatment for patients with unresectable or metastatic soft tissue sarcoma

  • PHASE II STUDIES
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Summary

Background Tasisulam sodium (hereafter tasisulam), a novel anticancer agent, is being studied in a broad range of tumors. The primary objective of this phase II study was to determine progression-free survival (PFS) in patients with 1 or 2 prior chemotherapy regimens for unresectable/metastatic soft tissue sarcoma (STS). Secondary objectives included objective response rate (ORR), clinical benefit rate (CBR), overall survival (OS), pharmacokinetics, and safety. Methods Tasisulam was administered intravenously on day 1 of 21-day cycles according to a lean body weight–based dosing algorithm targeting a peak plasma concentration (Cmax) of 420 μg/mL; a 360-μg/mL dose level was also explored. Results The median age of patients treated at 420 μg/mL was 58.3 years (range, 18.6–80.4; n = 63). Median PFS was 2.64 months (90 % CI, 1.41–3.38), with a 6-month PFS rate of 11 % (90 % CI, 4–17). Median OS was 8.71 months (90 % CI, 7.39–16.23); ORR, 3.2 %; and CBR, 46.0 % (stable disease, n = 27; partial response/confirmed, n = 2 [angiosarcoma and leiomyosarcoma]; partial response/unconfirmed, n = 1 [desmoplastic small round cell tumor]). The most frequent drug-related grade 3/4 toxicities in patients treated at 420 μg/mL were thrombocytopenia (27.0 %) and neutropenia (22.2 %). Incidences of grade 4 thrombocytopenia and/or neutropenia were 20.6 % in patients treated at 420 μg/mL and 15.8 % in those treated at 360 μg/mL (n = 38). Conclusions Tasisulam at a target Cmax of 420 μg/mL on day 1 of 21-day cycles demonstrated modest activity as second-/third-line treatment in patients with STS. Grade 4 hematologic toxicity posed some challenges in these heavily pre-treated patients. Tasisulam dosing continues to be refined.

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Acknowledgements

We would like to thank the following investigators for their participation in the conduct of the study: Gabriela Cinat, Fundación Cidea Sanatorio San Jose, Buenos Aires, Argentina; Maria Pallotta, Hospital Italiano, Buenos Aires, Argentina; Carlos Silva, Hospital Británico de Buenos Aires, Buenos Aires, Argentina; Antonio Casado Herraez, Hospital Clínico San Carlos, Madrid, Spain; Javier Garcia del Muro, Hospital Duran Reynals, Barcelona, Spain; Shreyaskumar Patel, University of Texas MD Anderson Cancer Center, Houston, TX, USA; Pasquale Benedetto, Sylvester Comprehensive Cancer Center, Miami, FL, USA; John Hainsworth, Sarah Cannon Cancer Center, Nashville, TN, USA; Howard Bailey, University of Wisconsin-Madison, Madison, WI, USA; Vivek Sharma, University of Louisville, Louisville, KY, USA; Warren Chow, City of Hope National Medical Center, Duarte, CA, USA; Claire Vershraegen, The New Mexico Cancer Care Alliance, Albuquerque, NM, USA; and ACORN Research LLC: Laura Blakely, The West Clinic, Memphis, TN, USA; Arthur Staddon, Pennsylvania Hospital, Philadelphia, PA, USA; and Brian Samuels, Kootenai Cancer Center, Couer D’Alene, ID, USA. We would also like to thank Robert Maki, Mount Sinai Medical Center, New York, NY, USA, for his intellectual contributions to the preparation of this paper, Toni Miller of Eli Lilly and Company (currently at Aerotek, Inc) and Mary Spanke of Eli Lilly and Company for clinical trial management support, Yushan Liu of i3 Statprobe for statistical support, Kay Chow of Eli Lilly and Company for pharmacokinetic data support, and Svetlana Dominguez of Eli Lilly and Company for editorial support.

Conflict of interest

Other than normal reimbursements associated with clinical trial enrollment and conduct from Eli Lilly and Company, Indianapolis, IN, USA, Christopher Ryan, Chacon Matias, Mark Agulnik, Antonio Lopez-Pousa, Charles Williams, and Mary Lou Keohan have no relevant financial disclosures to report. Other than owning Lilly stock per their Lilly and Company employment, Sabine Ermisch, Dinesh de Alwis, Christopher Kaiser, Mary Alice Miller, and Robert Ilaria have no other relevant financial disclosures to report.

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Correspondence to Christopher W. Ryan.

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Eli Lilly and Company provided the funding for this research.

ClinicalTrials.gov Identifier: NCT00490451

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Ryan, C.W., Matias, C., Agulnik, M. et al. A phase II study of tasisulam sodium (LY573636 sodium) as second-line or third-line treatment for patients with unresectable or metastatic soft tissue sarcoma. Invest New Drugs 31, 145–151 (2013). https://doi.org/10.1007/s10637-012-9819-5

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