Monk B J, Brewer C, VanNostrand K, Berns M W, McCullough J L, Tadir Y, Manetta A
Department of Obstetrics and Gynecology, UCI Medical Center, Orange, California 92668, USA.
Gynecol Oncol. 1997 Jan;64(1):70-5. doi: 10.1006/gyno.1996.4463.
To perform a phase I study of topically applied dihematoporphyrin ether (DHE) in the photodynamic treatment (PDT) of cervical intraepithelial neoplasia (CIN) using fixed DHE doses and application schedules, and a variable dose of 630 nm red light delivered by an argon-pumped dye laser.
Between February 1993 and April 1994, 24 nonpregnant women with a histologic diagnosis of CIN were enrolled. All patients had lesions involving at least 25% of the cervix that were colposcopically visible. Using a cervical cap, 2 ml of a 1% solution of DHE (Photofrin) in a 4% Azone and isopropyl alcohol vehicle were applied to the cervix 24 hr prior to PDT. An argon-pumped dye laser providing light at 630 nm was then used to perform PDT. Light was coupled into a 400-microm silica fiber optic terminating in a microlens which focused the laser radiation onto a circular field of uniform light intensity perpendicular to the tissue. The entire ectocervix was treated in a single field including a margin of 3-5 mm of normal cervix. Using a constant power density (150 mW/cm2) to avoid thermal injury, the PDT energy was increased every 4 patients in a phase I fashion (40, 60, 80, 100, 120, and 140 J/cm2).
Thirteen patients with CIN I, 7 patients with CIN II, and 4 patients with CIN III were treated. The maximal energy density was well tolerated. Toxicity was minimal with no patients experiencing local necrosis, sloughing, or scarring; however, a mild vaginal discharge was noted in several patients. Systemic effects were absent. After 12 months of follow-up at 3-month intervals, 22 patients are evaluable of whom 15 (68%) are disease free. One patient was lost to follow-up and in another the cervical cap was dislodged. Four of the 7 failures or recurrences occurred at energy densities of 80 J/cm2 or less, while 8 of 11 (73%) patients were treated successfully with PDT at an energy density of 100 to 140 J/cm2.
PDT with DHE and an argon-pumped dye laser at 630-nm wavelength delivering an energy density of 140 J/cm2 is safe and effective in treating CIN. Phase II studies using PDT at the prescribed application schedule and dose are indicated.
采用固定的二血卟啉醚（DHE）剂量和给药方案，以及由氩离子泵浦染料激光提供的可变剂量630nm红光，对宫颈上皮内瘤变（CIN）进行光动力治疗（PDT）的I期研究。
1993年2月至1994年4月，招募了24例经组织学诊断为CIN的非妊娠女性。所有患者的病变在阴道镜下可见，累及至少25%的宫颈。在PDT前24小时，使用宫颈帽将2ml含1% DHE（光卟啉）的溶液置于4%氮酮和异丙醇载体中，涂抹于宫颈。然后使用提供630nm光的氩离子泵浦染料激光进行PDT。光通过一根400微米的石英光纤耦合到一个微透镜中，该微透镜将激光辐射聚焦到垂直于组织的均匀光强的圆形区域上。整个宫颈外口在一个视野中进行治疗，包括3 - 5mm正常宫颈边缘。为避免热损伤，使用恒定功率密度（150mW/cm²），以I期方式每4例患者增加一次PDT能量（40、60、80、100、120和140J/cm²）。
治疗了13例CIN I患者、7例CIN II患者和4例CIN III患者。最大能量密度耐受性良好。毒性极小，无患者出现局部坏死、脱落或瘢痕形成；然而，有几名患者出现轻度阴道分泌物。无全身影响。在以3个月为间隔的12个月随访后，22例患者可评估疗效，其中15例（68%）无疾病。1例患者失访，另1例宫颈帽脱落。7例治疗失败或复发的患者中有4例发生在能量密度80J/cm²或更低时，而11例患者中有8例（73%）在能量密度100至140J/cm²时PDT治疗成功。
使用DHE和波长630nm的氩离子泵浦染料激光进行PDT，能量密度为140J/cm²，治疗CIN安全有效。建议按照规定的给药方案和剂量进行II期PDT研究。
