Authors' Affiliations: Photodynamic Therapy Center at the Department of Cell Stress Biology, Departments of Head and Neck Surgery, Molecular and Cellular Biology, Biostatistics and Bioinformatics, Dentistry, and Pathology, Roswell Park Cancer Institute (RPCI), Buffalo, New York.
Clin Cancer Res. 2013 Dec 1;19(23):6605-13. doi: 10.1158/1078-0432.CCR-13-1735. Epub 2013 Oct 2.
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, or early-stage HNSCC were enrolled in two sequentially conducted dose escalation studies with an expanded cohort at the highest dose level. These studies used an HPPH dose of 4 mg/m(2) and light doses from 50 to 140 J/cm(2). Pathologic tumor responses were assessed at 3 months. Clinical follow up range was 5 to 40 months. PDT induced cross-linking of 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 carcinoma in situ and 82% for squamous cell carcinomas (SCC) lesions at 140 J/cm(2). The responses in the carcinoma in situ/dysplasia cohort are not durable. The PDT-induced STAT3 cross-links is significantly higher (P = 0.0033) in SCC than in carcinoma in situ/dysplasia for all light doses.
HPPH-PDT is safe for the treatment of carcinoma in situ/dysplasia and early-stage cancer of the oral cavity. Early-stage oral HNSCC seems to respond better to HPPH-PDT in comparison with premalignant lesions. The degree of STAT3 cross-linking is a significant reporter to evaluate HPPH-PDT-mediated photoreaction.
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）治疗头颈部（HNSCC）异型增生和早期鳞状细胞癌的安全性。次要目标是评估治疗反应和报告有效的 PDT 反应的指标。
患有组织学证实的口腔异型增生、原位癌或早期 HNSCC 的患者被纳入两项连续的剂量递增研究中，在最高剂量水平时扩展了队列。这些研究使用 HPPH 剂量为 4mg/m2 和光剂量为 50-140J/cm2。病理肿瘤反应在 3 个月时评估。临床随访范围为 5 至 40 个月。评估了 PDT 诱导的 STAT3 交联作为 PDT 有效反应的潜在指标。
40 例患者接受了 HPPH-PDT 治疗。常见的不良反应是疼痛和治疗部位水肿。在 140J/cm2 时，活检证实异型增生和原位癌的完全缓解率分别为 46%，鳞状细胞癌（SCC）病变为 82%。原位癌/异型增生队列的反应不能持久。对于所有光剂量，SCC 中 PDT 诱导的 STAT3 交联明显高于原位癌/异型增生（P=0.0033）。
HPPH-PDT 治疗口腔原位癌/异型增生和早期癌症是安全的。与癌前病变相比，早期口腔 HNSCC 似乎对 HPPH-PDT 反应更好。STAT3 交联程度是评估 HPPH-PDT 介导的光反应的重要指标。
