A phase I study of Foscan-mediated photodynamic therapy and surgery in patients with mesothelioma.
BACKGROUND
Photodynamic therapy (PDT) is a light-based cancer treatment that, in the correct setting, can be delivered intraoperatively as an adjuvant therapy. A phase I clinical trial combining surgical debulking with Foscan-mediated PDT was performed in patients with malignant pleural mesothelioma. The purpose of the study was to define the toxicities and to determine the maximally tolerated dose (MTD) of Foscan-mediated PDT.


METHODS
A total of 26 patients completed treatment. Tumor debulking was accomplished with either an extrapleural pneumonectomy (7 patients) or a lung-sparing pleurectomy-decortication (19 patients). Patients were injected with Foscan before surgery, and 652 nm light was delivered intraoperatively after completion of surgical debulking. Four light sensors were placed in the chest, allowing delivery of light to a uniform measured dose throughout the hemithorax.


RESULTS
Four dose levels were explored. The MTD was 0.1 mg/kg of Foscan injected 6 days before surgery in combination with 10 J x cm(-2) 652 nm light. Dose limiting toxicity at the next higher dose was a systemic capillary leak syndrome leading to death in 2 of 3 patients treated at that dose. Other PDT-related toxicities included wound burns and skin photosensitivity. In all, 14 patients were treated at the MTD without significant complications.


CONCLUSIONS
Foscan-mediated PDT can be safely combined with surgery at the established MTD. Unlike most other surgery-based multimodal treatments for mesothelioma, Foscan-mediated PDT affords the option, in selected patients, of accomplishing tumor debulking with a lung-sparing procedure rather than an extrapleural pneumonectomy. A phase II study is warranted.
Friedberg
Joseph S
JS
Department of Surgery, Thomas Jefferson University Hospital, Philadelphia, Pennsylvania 19104-4283, USA. joseph.friedberg@mail.tju.edu
Mick
Rosemarie
R
Stevenson
James
J
Metz
James
J
Zhu
Timothy
T
Buyske
Jo
J
Sterman
Daniel H
DH
Pass
Harvey I
HI
Glatstein
Eli
E
Hahn
Stephen M
SM
D000368:Aged; D019559:Capillary Leak Syndrome / Q000139:chemically induced / Q000401:mortality; D002423:Cause of Death; D017024:Chemotherapy, Adjuvant; D003131:Combined Modality Therapy; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D006414:Hematoporphyrin Photoradiation / Q000009:adverse effects; D006801:Humans; D007432:Intraoperative Period; D008297:Male; D020714:Maximum Tolerated Dose; D008652:Mesoporphyrins / Q000009:adverse effects / Q000627:therapeutic use; D008654:Mesothelioma / Q000188:drug therapy* / Q000473:pathology / Q000601:surgery; D008875:Middle Aged; D009367:Neoplasm Staging; D010994:Pleura / Q000601:surgery; D010997:Pleural Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000601:surgery; D011013:Pneumonectomy; D011183:Postoperative Complications / Q000139:chemically induced / Q000401:mortality
D008652:Mesoporphyrins; C072269:temoporfin