Photodynamic therapy with 3-(1'-hexyloxyethyl) pyropheophorbide a for cancer of the oral cavity.
Photodynamic therapy with 3-(1'-hexyloxyethyl) pyropheophorbide a for cancer of the oral cavity.
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DOI：
10.1158/1078-0432.ccr-13-1735
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发表时间：
2013-12-01
期刊：
影响因子：
--
通讯作者：
Henderson BW
中科院分区：
文献类型：
--
作者：
Rigual N;Shafirstein G;Cooper MT;Baumann H;Bellnier DA;Sunar U;Tracy EC;Rohrbach DJ;Wilding G;Tan W;Sullivan M;Merzianu M;Henderson BW
主要目的是评估 3-(1’-己氧基乙基)焦脱镁叶绿酸-a (HPPH) 光动力疗法 (HPPH-PDT) 对于头颈发育不良和早期鳞状细胞癌 (HNSCC) 的安全性。次要目标是评估治疗反应和报告器以实现有效的 PDT 反应。组织学证实的口腔发育不良、原位癌 (CiS) 或早期 HNSCC 患者被纳入两项连续进行的剂量递增研究，并扩大了最高剂量水平的队列。这些研究采用 4 mg/m2 的 HPPH 剂量和 50 至 140 J/cm2 的光剂量。 3个月时评估病理肿瘤反应。临床随访范围为5至40个月。 PDT 诱导的信号转导子和转录激活子 3 (STAT3) 交联被评估为 PDT 有效反应的潜在指标。 40 名患者接受了 HPPH-PDT。常见的不良事件是疼痛和治疗部位水肿。活检证明，在 140 J/cm2 下，不典型增生和 CiS 的完全缓解率为 46%，SCC 病变的完全缓解率为 82%。 CiS/发育异常队列中的反应并不持久。对于所有光剂量，PDT 诱导的 STAT3 交联在 SCC 中显着高于 CiS/发育不良中 (P=0.0033)。 HPPH-PDT 对于治疗 CiS/发育不良和早期口腔癌是安全的。与癌前病变相比，早期口腔 HNSCC 对 HPPH-PDT 的反应似乎更好。 STAT3 交联程度是评估 HPPH-PDT 介导的光反应的重要报告。
The primary objective was to evaluate safety of 3-(1’-hexyloxyethyl)pyropheophorbide-a (HPPH) photodynamic therapy (HPPH-PDT) for dysplasia and early squamous cell carcinoma of the head and neck (HNSCC). Secondary objectives were the assessment of treatment response and reporters for an effective PDT reaction. Patients with histologically proven oral dysplasia, carcinoma in situ (CiS ) or early stage HNSCC were enrolled in two sequentially conducted dose escalation studies with an expanded cohort at the highest dose level. These studies employed an HPPH dose of 4 mg/m2 and light doses from 50 to 140 J/cm2. Pathologic tumor responses were assessed at 3 months. Clinical follow up range was 5 to 40 months. PDT induced cross-linking of signal transducer and activator of transcription 3 (STAT3) were assessed as potential indicators of PDT effective reaction. Forty patients received HPPH-PDT. Common adverse events were pain and treatment site edema. Biopsy proven complete response rates were 46% for dysplasia and CiS, and 82% for SCCs lesions at 140 J/cm2. The responses in the CiS/dysplasia cohort are not durable. The PDT induced STAT3 cross-links is significantly higher (P=0.0033) in SCC than in CiS/dysplasia for all light-doses. HPPH-PDT is safe for the treatment of CiS/dysplasia and early stage cancer of the oral cavity. Early stage oral HNSCC appears to respond better to HPPH-PDT in comparison to premalignant lesions. The degree of STAT3 cross-linking is a significant reporter to evaluate HPPH-PDT mediated photoreaction.