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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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Related in: MedlinePlus

Vital sign data for the 3 cohorts at screening and throughout the infusion. (a) Body temperature, (b) respiration, (c) pulsation, (d) diastolic pressure, and (e) systolic pressure at the 3 different doses: 56 mg/m2 (n = 3), 74 mg/m2 (n = 14), and 98 mg/m2 (n = 4).
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fig2: Vital sign data for the 3 cohorts at screening and throughout the infusion. (a) Body temperature, (b) respiration, (c) pulsation, (d) diastolic pressure, and (e) systolic pressure at the 3 different doses: 56 mg/m2 (n = 3), 74 mg/m2 (n = 14), and 98 mg/m2 (n = 4).

Mentions: Tolerability and toxicity were evaluated for all subjects. The vital sign data showed that all values fluctuated within the normal range at every time point among the 3 cohorts (Figure 2). All hematological parameters (Fbg, PT) and results of electrocardiography and routine stool test were normal. Only 1 patient experienced grade 1 microscopic hematuria, while 2 subjects developed grade 1 proteinuria after 2 cycles of treatment with UAL (74 mg/m2).


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)

Vital sign data for the 3 cohorts at screening and throughout the infusion. (a) Body temperature, (b) respiration, (c) pulsation, (d) diastolic pressure, and (e) systolic pressure at the 3 different doses: 56 mg/m2 (n = 3), 74 mg/m2 (n = 14), and 98 mg/m2 (n = 4).
© Copyright Policy
Related In: Results  -  Collection

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

fig2: Vital sign data for the 3 cohorts at screening and throughout the infusion. (a) Body temperature, (b) respiration, (c) pulsation, (d) diastolic pressure, and (e) systolic pressure at the 3 different doses: 56 mg/m2 (n = 3), 74 mg/m2 (n = 14), and 98 mg/m2 (n = 4).
Mentions: Tolerability and toxicity were evaluated for all subjects. The vital sign data showed that all values fluctuated within the normal range at every time point among the 3 cohorts (Figure 2). All hematological parameters (Fbg, PT) and results of electrocardiography and routine stool test were normal. Only 1 patient experienced grade 1 microscopic hematuria, while 2 subjects developed grade 1 proteinuria after 2 cycles of treatment with UAL (74 mg/m2).

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