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

Christopher W. Ryan, Chacon Matias, Mark Agulnik, Antonio Lopez-Pousa, Charles Williams, Dinesh P. De Alwis, Christopher Kaiser, Mary Alice Miller, Sabine Ermisch, Robert Ilaria, M. L. Keohan

    Research output: Contribution to journalArticle

    6 Scopus citations

    Abstract

    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 C max 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.

    Original languageEnglish (US)
    Pages (from-to)145-151
    Number of pages7
    JournalInvestigational New Drugs
    Volume31
    Issue number1
    DOIs
    StatePublished - Feb 1 2013

    Keywords

    • LY573636
    • Second- and third-line treatment
    • Soft tissue sarcoma
    • Tasisulam

    ASJC Scopus subject areas

    • Oncology
    • Pharmacology
    • Pharmacology (medical)

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    Ryan, C. W., Matias, C., Agulnik, M., Lopez-Pousa, A., Williams, C., De Alwis, D. P., Kaiser, C., Miller, M. A., Ermisch, S., Ilaria, R., & Keohan, M. L. (2013). 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. Investigational New Drugs, 31(1), 145-151. https://doi.org/10.1007/s10637-012-9819-5