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: 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 Jr, M L Keohan
• Journal: Investigational new drugs (Invest New Drugs) Vol. 31 Issue 1 Pg. 145-51 (Feb 2013) ISSN: 1573-0646 [Electronic] United States
• PMID: 22539091 (Publication Type: Clinical Trial, Phase II, Journal Article, Multicenter Study)

Chemical References

• Antineoplastic Agents
• Benzamides
• N-((5-bromo-2-thienyl)sulfonyl)-2,4-dichlorobenzamide
• Sulfonamides

Topics

• Adolescent
• Adult
• Aged
• Aged, 80 and over
• Antineoplastic Agents (pharmacokinetics, therapeutic use)
• Benzamides (pharmacokinetics, therapeutic use)
• Disease-Free Survival
• Female
• Humans
• Male
• Middle Aged
• Sarcoma (blood, drug therapy)
• Sulfonamides (pharmacokinetics, therapeutic use)
• Young Adult