使用2-[1-己氧基乙基]-2-去乙烯基焦脱镁叶绿酸-a进行光动力疗法治疗原位非小细胞癌或非小细胞微浸润性支气管源性癌的低剂量I期研究：剂量范围研究
A Phase I Study of Light Dose for Photodynamic Therapy Using 2-[1-Hexyloxyethyl]-2 Devinyl Pyropheophorbide-a for the Treatment of Non-Small Cell Carcinoma In Situ or Non-Small Cell Microinvasive Bronchogenic Carcinoma: A Dose Ranging Study.
作者信息
Dhillon Samjot Singh, Demmy Todd L, Yendamuri Sai, Loewen Gregory, Nwogu Chukwumere, Cooper Michele, Henderson Barbara W
机构信息
Department of Medicine-Pulmonary Medicine/Thoracic Oncology, Roswell Park Cancer Institute, Buffalo, NY.
Sections of Thoracic Oncology and Thoracic Surgery, Department of Surgery, Robert Wood Johnson Medical School, New Brunswick, NJ.
出版信息
J Thorac Oncol. 2016 Feb;11(2):234-41. doi: 10.1016/j.jtho.2015.10.020. Epub 2015 Dec 22.
INTRODUCTION
We report a phase I trial of photodynamic therapy (PDT) of carcinoma in situ (CIS) and microinvasive cancer (MIC) of the central airways with the photosensitizer (PS) 2-[1-hexyloxyethyl]-2-devinyl pyropheophorbide-a (HPPH). HPPH has the advantage of minimal general phototoxicity over the commonly used photosensitizer porfimer sodium (Photofrin; Pinnacle Biologics, Chicago, IL).
METHODS
The objectives of this study were (1) to determine the maximally tolerated light dose at a fixed photosensitizer dose and (2) to gain initial insight into the effectiveness of this treatment approach. Seventeen patients with 21 CIS/MIC lesions were treated with HPPH with light dose escalation starting from 75 J/cm2 and increasing to 85, 95,125, and 150 J/cm2 respectively. Follow-up bronchoscopy for response assessment was performed at 1 and 6 months, respectively.
RESULTS
The rate of pathological complete response (CR) was 82.4% (14 of 17 evaluable lesions; 14 patients) at 1 month and 72.7% (8/11 evaluable lesions; 8 patients) at 6 months. Only four patients developed mild skin erythema. One of the three patients in the 150 J/cm2 light dose group experienced a serious adverse event. This patient had respiratory distress caused by mucus plugging, which precipitated cardiac ischemia. Two additional patients treated subsequently at this light dose had no adverse events. The sixth patient in this dose group was not recruited and the study was terminated because of delays in HPPH supply. However, given the observed serious adverse event, it is recommended that the light dose does not exceed 125 J/cm2.
CONCLUSIONS
PDT with HPPH can be safely used for the treatment of CIS/MIC of the airways, with potential effectiveness comparable to that reported for porfimer sodium in earlier studies.
引言
我们报告了一项使用光敏剂2-[1-己氧基乙基]-2-去乙烯基焦脱镁叶绿酸-a（HPPH）对中央气道原位癌（CIS）和微浸润癌（MIC）进行光动力疗法（PDT）的I期试验。与常用的光敏剂卟吩姆钠（Photofrin；Pinnacle Biologics，芝加哥，伊利诺伊州）相比，HPPH具有最小全身光毒性的优势。
方法
本研究的目的是（1）在固定光敏剂剂量下确定最大耐受光剂量，以及（2）初步了解这种治疗方法的有效性。17例患有21处CIS/MIC病变的患者接受了HPPH治疗，光剂量从75 J/cm²开始逐步递增，分别增至85、95、125和150 J/cm²。分别在1个月和6个月时进行随访支气管镜检查以评估反应。
结果
1个月时病理完全缓解（CR）率为82.4%（17处可评估病变中的14处；14例患者），6个月时为72.7%（11处可评估病变中的8处；8例患者）。仅4例患者出现轻度皮肤红斑。150 J/cm²光剂量组的3例患者中有1例发生严重不良事件。该患者因黏液阻塞导致呼吸窘迫，进而引发心脏缺血。随后接受此光剂量治疗的另外2例患者未发生不良事件。该剂量组的第6例患者未纳入研究，且由于HPPH供应延迟研究终止。然而，鉴于观察到的严重不良事件，建议光剂量不超过125 J/cm²。
结论
使用HPPH的PDT可安全用于气道CIS/MIC的治疗，其潜在有效性与早期研究中报道的卟吩姆钠相当。
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