Hahn Stephen M, Fraker Douglas L, Mick Rosemarie, Metz James, Busch Theresa M, Smith Debbie, Zhu Timothy, Rodriguez Carmen, Dimofte Andreea, Spitz Francis, Putt Mary, Rubin Stephen C, Menon Chandrakala, Wang Hsing-Wen, Shin Daniel, Yodh Arjun, Glatstein Eli
Department of Radiation Oncology, Division of Gynecologic Oncology, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Clin Cancer Res. 2006 Apr 15;12(8):2517-25. doi: 10.1158/1078-0432.CCR-05-1625.
A previous phase I trial of i.p. photodynamic therapy established the maximally tolerated dose of Photofrin (Axcan Pharma, Birmingham, AL)-mediated photodynamic therapy and showed encouraging efficacy. The primary objectives of this phase II study were to determine the efficacy and toxicities of i.p. photodynamic therapy in patients with peritoneal carcinomatosis and sarcomatosis.
Patients received Photofrin 2.5 mg/kg i.v. 48 hours before debulking surgery. Intraoperative laser light was delivered to the peritoneal surfaces of the abdomen and pelvis. The outcomes of interest were (a) complete response, (b) failure-free survival time, and (c) overall survival time. Photosensitizer levels in tumor and normal tissues were measured.
One hundred patients were enrolled into one of three strata (33 ovarian, 37 gastrointestinal, and 30 sarcoma). Twenty-nine patients did not receive light treatment. All 100 patients had progressed by the time of statistical analysis. The median failure-free survival and overall survival by strata were ovarian, 2.1 and 20.1 months; gastrointestinal cancers, 1.8 and 11.1 months; sarcoma, 3.7 and 21.9 months. Substantial fluid shifts were observed postoperatively, and the major toxicities were related to volume overload. Two patients died in the immediate postoperative period from bleeding, sepsis, adult respiratory distress syndrome, and cardiac ischemia.
Intraperitoneal Photofrin-mediated photodynamic therapy is feasible but does not lead to significant objective complete responses or long-term tumor control. Heterogeneity in photosensitizer uptake and tumor oxygenation, lack of tumor specificity for photosensitizer uptake, and the heterogeneity in tissue optical properties may account for the lack of efficacy observed.
先前一项关于腹腔内光动力疗法的I期试验确定了卟吩姆钠（Axcan制药公司，阿拉巴马州伯明翰）介导的光动力疗法的最大耐受剂量，并显示出令人鼓舞的疗效。这项II期研究的主要目的是确定腹腔内光动力疗法对腹膜癌和肉瘤患者的疗效及毒性。
患者在减瘤手术前48小时静脉注射2.5mg/kg卟吩姆钠。术中将激光照射至腹部和盆腔的腹膜表面。感兴趣的结果包括：（a）完全缓解；（b）无进展生存期；（c）总生存期。测量肿瘤和正常组织中的光敏剂水平。
100名患者被纳入三个分层之一（33例卵巢癌、37例胃肠道癌和30例肉瘤）。29名患者未接受光治疗。在进行统计分析时，所有100名患者均已进展。各分层的无进展生存期和总生存期的中位数分别为：卵巢癌，2.1个月和20.1个月；胃肠道癌，1.8个月和11.1个月；肉瘤，3.7个月和21.9个月。术后观察到大量体液转移，主要毒性与容量超负荷有关。两名患者在术后即刻因出血、败血症、成人呼吸窘迫综合征和心脏缺血死亡。
腹腔内卟吩姆钠介导的光动力疗法是可行的，但不会导致显著的客观完全缓解或长期肿瘤控制。光敏剂摄取和肿瘤氧合的异质性、光敏剂摄取缺乏肿瘤特异性以及组织光学特性的异质性可能是观察到疗效不佳的原因。
