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Zhao Y.,Peking University | Tu P.,Peking University | Zhou G.,Shanghai JiaoTong University | Zhou Z.,Peking Union Medical College | And 10 more authors.
PLoS ONE | Year: 2016

Background and Objectives: Photodynamic therapy (PDT) has shown potentially beneficial results in treating port-wine stain, but its benefit-risk profile remains undefined. This study aimed to evaluate the efficacy and safety of PDT conducted with hemoporfin and a 532 nm continuous wave laser to treat port-wine stain clinically. Patients and Methods: This randomized clinical trial was conducted in eight hospitals in China. Participants were adolescent and adult patients (age range: 14-65 years old) with port-wine stain. During stage 1 (day 1 to week 8) all patients were randomized at a 3:1 ratio to treatment (532 nm laser irradiation (96-120 J/cm2) with hemoporfin (5mg/kg; PDT-hemoporfin, n = 330)) or placebo groups (irradiation with placebo (PDT-placebo, n = 110)); during stage 2 (week 8 to 16) patients in both groups were offered treatment. Clinician-evaluators, who were blind to the study, classified each case on the following four-level scale according to assessment of before and after standardized pictures of the lesion area: no improvement: <20%; some improvement: 20-59%; great improvement: 60-89%; or nearly completely resolved: ≥90%. The primary efficacy endpoint was proportion of patients achieving at least some improvement at week 8. The secondary efficacy endpoints were proportion of patients achieving nearly completely resolved or at least great improvement at week 8, proportion of patients achieving early completely resolved, at least great improvement, or at least some improvement at week 16, and the corresponding satisfaction of the investigators and the patients (designated as 'excellent', 'good', 'moderate', or'ineffective') at weeks 8 and 16. Results: Compared to the PDT-placebo group, the PDT-hemoporfin group showed a significantly higher proportion of patients that achieved at least some improvement (89.7% [n = 295; 95% CI, 85.9%-92.5%] vs. 24.5% [n = 27; 95% CI, 17.4%-33.3%]) at week 8 (P > 0.0001) and higher improvements for all secondary efficacy endpoints. Treatment reactions occurred in 99.5% (n = 731; 95% CI, 98.7%-99.8%) of the PDT-hemoporfin treatments (n = 735). Hyperpigmentation occurred in 22.9 per 100 patient-treatments (n = 168; 95% CI, 20.0-26.0) in the PDT-hemoporfin treated patients. Conclusions: Hemoporfin-mediated PDT is an effective and safe treatment option for adolescent and adult patients with port-wine stain. Trial Registration: Chinese Clinical Trial Registry ChiCTR-TRC-08000213. © 2016 Zhao et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Sun P.-H.,Peking University | Zhao X.,Peking University | Zhou Y.,Peking University | Liang Y.,Peking University | And 3 more authors.
Acta Pharmacologica Sinica | Year: 2011

Aim: To investigate the safety, tolerability and pharmacokinetics of intravenous hemoporfin, a novel photosensitive drug for the treatment of port-wine stain (PWS), in healthy Chinese volunteers following single-dose administration. Methods: Thirty-six healthy Chinese subjects were enrolled. The subjects were administered hemoporfin (2.5, 5, 7.5 or 10 mg/kg) via single-dose intravenous infusion. Pharmacokinetics of the drug were studied in the groups with doses of 2.5, 5 and 7.5 mg/kg, and tolerability was studied in all the 4 groups. Safety and tolerance were evaluated by monitoring adverse events and laboratory parameters, and pharmacokinetics were assessed by determining hemoporfin content with a validated high-performance liquid chromatography with uorescence detection (HPLC/FLD) method. Results: Mild and transient adverse events occurred in the trial (n=10), but none were serious, and no subjects were withdrawn from the trial. The gastrointestinal tract adverse events, such as nausea, stomach upset, abdominal pain and vomiting, were observed in the groups with doses of 7.5 and 10 mg/kg. Increased alanine aminotransferase (ALT) concentration was found in 3 subjects, and increased alkaline phosphatase (ALP) concentration in one subject. The half-life of hemoporfin for doses of 2.5, 5, and 7.5 mg/kg was 1.26 h, 1.31 h, and 1.70 h, respectively. C max and AUC increased with dose for intravenous single-dose administration of hemoporfin in the 2.5, 5, and 7.5 mg/kg groups. Urinary excretion of hemoporfin within 12 h was less than 0.2%. Conclusion: Hemoporfin is safe and well-tolerated in healthy Chinese volunteers at a single intravenous dose of up to 10 mg/kg. It was rapidly cleared from the blood and had a short half-life, which insures a short light-avoidance period. © 2011 CPS and SIMM All rights reserved.

Zhao Y.,Peking University | Zhou Z.,Peking Union Medical College | Zhou G.,Shanghai JiaoTong University | Tu P.,Peking University | And 4 more authors.
Photodermatology Photoimmunology and Photomedicine | Year: 2011

Background/purpose: This phase IIa study aimed to study the efficacy and safety of hemoporfin in photodynamic therapy (PDT) with a 532 nm continuous laser for port-wine stain (PWS).Methods: In this 8-week open-labeled study in three centers, three different laser exposure times (532 nm continuous laser for 20, 30 and 40 min) were used in stage I, group A, stage II, group B and stage III, group C, respectively. Primary efficacy assessment was performed by an independent group of experts, who reviewed the standardized photos. Secondary efficacy assessment consisted of the subjective grading of the PWS fading by the investigators and the patients. Treatment reactions and adverse events (AE) were recorded separately.Results: Forty patients were initially enrolled in the study, but stage III had to be cancelled eventually for the safety of the patients. Patients in groups A and B showed similar satisfactory results in efficacy assessments, the total 'response' rate being 80.0% and 94.7% in groups A and B, respectively. The AE rates were also similar in the two groups. Self-limiting photosensitive dermatitis and hyperpigmentation were the most frequently observed AE.Conclusion: Hemoporfin-PDT is effective and safe for patients with PWS aged 16-50. © 2011 John Wiley & Sons A/S.

Zhao Y.,Peking University | Tao J.,Shanghai Fudan Zhangjiang Bio pharmaceutical Co. | Tu P.,Peking University
Photodiagnosis and Photodynamic Therapy | Year: 2013

Background: Methods for quantitatively evaluate the efficacy of photodynamic therapy (PDT) for port-wine stains (PWS) are still needed for clinical practice and studies. Methods: 50 pairs of pictures before and after PDT of 40 PWS patients were selected. Each PWS lesion was labeled with a marker of red color graded 0-9. These pictures were taken without assistance of instruments to keep same position or distance and were referred to as 'experimental' images. 70 labels were photographed at a fixed position and distance with the assistance of a bracket and the images obtained were referred to as 'standardized' ones. An independent group of three experts viewed the photos and assessed the efficacy. The images were processed and measured for erythema index (EI) with the ImageJ freeware. The EI difference (ΔEI) and the percent change of ΔEI (ratioΔEI(%)) of the labels and the PWS lesions was computed separately. Results: Significant differences of EI, ΔEI and ratioΔEI(%) were found between each two grades of the color markers in both standardized and experimental images. ΔEI of lesions achieved 'almost cured' and 'great improvement' after PDT was significantly reduced than before PDT. Significantly greater percentages of lesions were assessed as 'response' and 'significant response' in those of beforeΔEI≥35 compared to those of beforeΔEI<35. The ratioΔEI(%) decrease of lesions assessed as 'almost cured', 'great improvement' and 'some improvement' was significantly reduced sequentially. Conclusion: The EI image analysis is a valid method for quantitatively evaluating efficacy of PDT for PWS. © 2012 Elsevier B.V.

Zhong J.,Shanghai University of Traditional Chinese Medicine | Mao W.,Shanghai Fudan Zhangjiang Bio pharmaceutical Co. | Shi R.,Shanghai University of Traditional Chinese Medicine | Jiang P.,Shanghai University of Traditional Chinese Medicine | And 4 more authors.
Cancer Chemotherapy and Pharmacology | Year: 2014

Purpose: Vincristine sulfate (VCR) is a potent and widely used anti-tumor drug. Encapsulating VCR with liposomes improves its therapeutic index. However, there is little known about the pharmacokinetic features of un-encapsulated VCR (UE-VCR) and encapsulated VCR (E-VCR). Methods: Two groups of beagle dogs were intravenously administered a single 0.07 mg/kg dose of VCR liposomal injection (L-VCR) and VCR ordinary injection (I-VCR), respectively. The concentrations of UE-VCR, E-VCR and total VCR (T-VCR) were determined by separating UE-VCR and E-VCR, using solid-phase extraction and validated liquid chromatography-tandem mass spectrometry-based methods. Pharmacokinetic parameters were calculated, using the compartment model. The pharmacokinetic parameters of L-VCR and I-VCR were compared using a Student's t test. Results: After intravenous injection of L-VCR, the pharmacokinetic parameters of E-VCR were similar to those of T-VCR. The concentrations of UE-VCR were very low, and its AUC0-72h was only 2.5 % that of T-VCR. Compared with I-VCR, plasma AUC of E-VCR increased, with significantly extended distribution t1/2 and reduced distribution volume of the peripheral department. C2 min and AUC 0-1h of plasma UE-VCR decreased, with a similar elimination t1/2. Conclusions: The increased therapeutic index of L-VCR is demonstrated by the pharmacokinetic features, higher exposure to E-VCR and lower peak concentration of UE-VCR, following intravenous injection. © 2013 Springer-Verlag.

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