title: 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.
abstract: 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 (C(max)) 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.
authors.affiliation: Section of Hematology/Oncology, Oregon Health and Science University Knight Cancer Institute, Portland, OR, USA. ryanc@ohsu.edu
authors.forename: Christopher W
authors.initials: CW
authors.lastname: Ryan
authors.forename: Chacon
authors.initials: C
authors.lastname: Matias
authors.forename: Mark
authors.initials: M
authors.lastname: Agulnik
authors.forename: Antonio
authors.initials: A
authors.lastname: Lopez-Pousa
authors.forename: Charles
authors.initials: C
authors.lastname: Williams
authors.forename: Dinesh P
authors.initials: DP
authors.lastname: de Alwis
authors.forename: Christopher
authors.initials: C
authors.lastname: Kaiser
authors.forename: Mary Alice
authors.initials: MA
authors.lastname: Miller
authors.forename: Sabine
authors.initials: S
authors.lastname: Ermisch
authors.forename: Robert
authors.initials: R
authors.lastname: Ilaria
authors.forename: M L
authors.initials: ML
authors.lastname: Keohan
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000493:pharmacokinetics / Q000627:therapeutic use*; D001549:Benzamides / Q000493:pharmacokinetics / Q000627:therapeutic use*; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D012509:Sarcoma / Q000097:blood / Q000188:drug therapy*; D013449:Sulfonamides / Q000493:pharmacokinetics / Q000627:therapeutic use*; D055815:Young Adult
chemical_list: D000970:Antineoplastic Agents; D001549:Benzamides; C534068:N-((5-bromo-2-thienyl)sulfonyl)-2,4-dichlorobenzamide; D013449:Sulfonamides