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A phase I trial to evaluate the multiple-dose safety and antitumor activity of ursolic acid liposomes in subjects with advanced solid tumors.

Qian Z, Wang X, Song Z, Zhang H, Zhou S, Zhao J, Wang H - Biomed Res Int (2015)

Bottom Line: No ≥grade 3 adverse events (NCI-CTC) were observed.Sixty percent subjects achieved stable disease after 2 treatment cycles.Multiple-dose pharmacokinetic analysis suggested UAL does not accumulate in the body.

View Article: PubMed Central - PubMed

Affiliation: Department of Lymphoma, Sino-US Center for Lymphoma and Leukemia, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center of Cancer, Key Laboratory of Cancer Prevention and Therapy, Tiyuanbei, Huanhuxi Road, Hexi District, Tianjin 300060, China.

ABSTRACT
Ursolic acid liposome (UAL), a new antitumor drug, has potential therapeutic value. However, limited clinical data exists regarding multiple-dose safety, antitumor activity, and the recommended dose (RD) of UAL for subjects with advanced solid tumors. All subjects were intravenously administered UAL for 14 consecutive days of a 21-day treatment cycle. Twenty-one subjects were enrolled in 1 of 3 sequential cohorts (56, 74, and 98 mg/m(2)) to evaluate multiple-dose tolerability and efficacy. Eight additional subjects were treated with UAL (74 mg/m(2)) to evaluate multiple-dose pharmacokinetics. No ≥grade 3 adverse events (NCI-CTC) were observed. Sixty percent subjects achieved stable disease after 2 treatment cycles. Multiple-dose pharmacokinetic analysis suggested UAL does not accumulate in the body. This trial demonstrates that UAL was tolerable, had manageable toxicity, and could potentially improve patient remission rates. A large phase II study is recommended to confirm these results (i.e., RD of 98 mg/m(2)).

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The chemical structure of ursolic acid.
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fig1: The chemical structure of ursolic acid.

Mentions: Ursolic acid (UA) is a natural hydroxy pentacyclic triterpene compound (Figure 1) isolated from Chinese herbs including Eriobotrya japonica, Rosmarinus officinalis, and Glechoma hederacea [1, 2]. Previous studies have indicated that UA can induce apoptosis [3–5] and cell differentiation [6, 7], inhibit invasion and metastasis [8], and inhibit angiogenesis [9–11] in various tumors. UA treatment is also safe [12]. Thus, UA is a potentially valuable compound. However, the poor solubility of UA in hydrous solutions greatly limits its applications.


A phase I trial to evaluate the multiple-dose safety and antitumor activity of ursolic acid liposomes in subjects with advanced solid tumors.

Qian Z, Wang X, Song Z, Zhang H, Zhou S, Zhao J, Wang H - Biomed Res Int (2015)

The chemical structure of ursolic acid.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4383362&req=5

fig1: The chemical structure of ursolic acid.
Mentions: Ursolic acid (UA) is a natural hydroxy pentacyclic triterpene compound (Figure 1) isolated from Chinese herbs including Eriobotrya japonica, Rosmarinus officinalis, and Glechoma hederacea [1, 2]. Previous studies have indicated that UA can induce apoptosis [3–5] and cell differentiation [6, 7], inhibit invasion and metastasis [8], and inhibit angiogenesis [9–11] in various tumors. UA treatment is also safe [12]. Thus, UA is a potentially valuable compound. However, the poor solubility of UA in hydrous solutions greatly limits its applications.

Bottom Line: No ≥grade 3 adverse events (NCI-CTC) were observed.Sixty percent subjects achieved stable disease after 2 treatment cycles.Multiple-dose pharmacokinetic analysis suggested UAL does not accumulate in the body.

View Article: PubMed Central - PubMed

Affiliation: Department of Lymphoma, Sino-US Center for Lymphoma and Leukemia, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center of Cancer, Key Laboratory of Cancer Prevention and Therapy, Tiyuanbei, Huanhuxi Road, Hexi District, Tianjin 300060, China.

ABSTRACT
Ursolic acid liposome (UAL), a new antitumor drug, has potential therapeutic value. However, limited clinical data exists regarding multiple-dose safety, antitumor activity, and the recommended dose (RD) of UAL for subjects with advanced solid tumors. All subjects were intravenously administered UAL for 14 consecutive days of a 21-day treatment cycle. Twenty-one subjects were enrolled in 1 of 3 sequential cohorts (56, 74, and 98 mg/m(2)) to evaluate multiple-dose tolerability and efficacy. Eight additional subjects were treated with UAL (74 mg/m(2)) to evaluate multiple-dose pharmacokinetics. No ≥grade 3 adverse events (NCI-CTC) were observed. Sixty percent subjects achieved stable disease after 2 treatment cycles. Multiple-dose pharmacokinetic analysis suggested UAL does not accumulate in the body. This trial demonstrates that UAL was tolerable, had manageable toxicity, and could potentially improve patient remission rates. A large phase II study is recommended to confirm these results (i.e., RD of 98 mg/m(2)).

Show MeSH
Related in: MedlinePlus