减瘤手术联合光动力疗法治疗播散性腹膜肿瘤的I期研究

Phase I study of debulking surgery and photodynamic therapy for disseminated intraperitoneal tumors.

作者信息

DeLaney T F, Sindelar W F, Tochner Z, Smith P D, Friauf W S, Thomas G, Dachowski L, Cole J W, Steinberg S M, Glatstein E

机构信息

Radiation Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892.

出版信息

Int J Radiat Oncol Biol Phys. 1993 Feb 15;25(3):445-57. doi: 10.1016/0360-3016(93)90066-5.

DOI:10.1016/0360-3016(93)90066-5

PMID:8436523

Abstract

PURPOSE

Phase I study designed to determine the maximum tolerated dose of intraoperative photodynamic therapy (PDT) at laparotomy/debulking surgery in patients with refractory or recurrent, disseminated intraperitoneal tumors.

METHODS AND MATERIALS

Patients received dihematoporphyrin ethers (DHE) 1.5-2.5 mg/kg by i.v. injection prior to surgery. Patients resected to < or = 5 mm of residual disease underwent laser light delivery to all peritoneal surfaces.

RESULTS

Fifty-four patients entered the study. Thirty-nine underwent resection and light delivery/PDT. PDT dose was escalated by increasing DHE from 1.5 to 2.5 mg/kg, shortening the interval between DHE injection and surgery from 72 to 48 hr, and increasing the light dose. Initially, 630 nm red light alone was used. In this group, PDT of 2.8-3.0 J/cm2 induced small bowel edema and resulted in 3 small bowel perforations after bowel resection or enterotomy. Further light dose escalation, however, was achieved by switching to less penetrating 514 nm green light to the bowel/mesentery. In later patients, whole peritoneal PDT was supplemented with boost doses of 10-15 J/cm2 red light or 5-7.5 J/cm2 green light to high risk areas. Small bowel complications were not seen after switching to less penetrating green light. Dose limiting toxicities occurred in 2 of 3 patients at the highest light dose of 5.0 J/cm2 green light with boost. These patients had pleural effusions that required thoracentesis and postoperative respiratory support for 7-9 days, while one had a gastric perforation. At potential follow-up times of 3.8-43.1 months (median 22.1 months), 30/39 patients are alive and 9/39 are free of disease.

CONCLUSION

The maximum tolerated dose of intraoperative PDT following debulking surgery performed 48 hr after intravenous administration 2.5 mg/kg DHE is 3.75 J/cm2 of 514 nm green light to the entire peritoneal surface with boosts to 5.0-7.5 J/cm2 of 514 nm green light or 10-15 J/cm2 of 630 nm red light to sites of gross disease encountered at surgery.

摘要

目的

开展一项I期研究，以确定在剖腹探查/减瘤手术中，对难治性或复发性、播散性腹膜内肿瘤患者进行术中光动力疗法（PDT）的最大耐受剂量。

方法和材料

患者在手术前静脉注射二血卟啉醚（DHE）1.5 - 2.5 mg/kg。残留病灶切除至≤5 mm的患者对所有腹膜表面进行激光照射。

结果

54例患者进入研究。39例接受了切除及光照射/PDT。通过将DHE从1.5 mg/kg增加至2.5 mg/kg、将DHE注射与手术之间的间隔从72小时缩短至48小时以及增加光剂量来提高PDT剂量。最初，仅使用630 nm红光。在该组中，2.8 - 3.0 J/cm²的PDT导致小肠水肿，并在肠切除或肠切开术后导致3例小肠穿孔。然而，通过改用穿透性较差的514 nm绿光照射肠/肠系膜实现了进一步的光剂量增加。在后来的患者中，全腹膜PDT辅以对高风险区域给予10 - 15 J/cm²红光或5 - 7.5 J/cm²绿光的增强剂量。改用穿透性较差的绿光后未出现小肠并发症。在最高光剂量为5.0 J/cm²绿光并给予增强剂量的3例患者中有2例出现剂量限制性毒性。这些患者出现胸腔积液，需要进行胸腔穿刺术并术后呼吸支持7 - 9天，其中1例出现胃穿孔。在3.8 - 43.1个月（中位时间22.1个月）的潜在随访期内，39例患者中有30例存活，9例无疾病。