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Treatment of pleural malignancies by photo‐induction combined to systemic chemotherapy: Proof of concept on rodent lung tumors and feasibility study on porcine chest cavities
Author(s) -
Wang Xingyu,
Gronchi Fabrizio,
Bensimon Michael,
Mercier Thomas,
Decosterd Laurent Arthur,
Wagnières Georges,
Debefve Elodie,
Ris HansBeat,
Letovanec Igor,
Peters Solange,
Perentes Jean Yannis
Publication year - 2015
Publication title -
lasers in surgery and medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.888
H-Index - 112
eISSN - 1096-9101
pISSN - 0196-8092
DOI - 10.1002/lsm.22422
Subject(s) - medicine , pleural cavity , lung , mesothelioma , adenocarcinoma , sarcoma , cisplatin , chemotherapy , pathology , urology , surgery , cancer
Background Low‐dose, Visudyne®‐mediated photodynamic therapy (photo‐induction) was shown to selectively enhance tumor vessel transport causing increased uptake of systemically administered chemotherapy in various tumor types grown on rodent lungs. The present experiments explore the efficacy of photo‐induced vessel modulation combined to intravenous (IV) liposomal cisplatin (Lipoplatin®) on rodent lung tumors and the feasibility/toxicity of this approach in porcine chest cavities. Material and Methods Three groups of Fischer rats underwent orthotopic sarcoma ( n = 14), mesothelioma ( n = 14), or adenocarcinoma ( n = 12) implantation on the left lung. Half of the animals of each group had photo‐induction (0.0625 mg/kg Visudyne®, 10 J/cm 2 ) followed by IV administration of Lipoplatin® (5 mg/kg) and the other half received Lipoplatin® without photo‐induction. Then, two groups of minipigs underwent intrapleural thoracoscopic (VATS) photo‐induction (0.0625 mg/kg Visudyne®; 30 J/cm 2 hilum; 10 J/cm 2 apex/diaphragm) with in situ light dosimetry in combination with IV Lipoplatin® administration (5 mg/kg). Protocol I ( n = 6) received Lipoplatin® immediately after light delivery and Protocol II ( n = 9) 90 minutes before light delivery. Three additional animals received Lipoplatin® and VATS pleural biopsies but no photo‐induction (controls). Lipoplatin® concentrations were analyzed in blood and tissues before and at regular intervals after photo‐induction using inductively coupled plasma mass spectrometry. Results Photo‐induction selectively increased Lipoplatin® uptake in all orthotopic tumors. It significantly increased the ratio of tumor to lung Lipoplatin® concentration in sarcoma ( P = 0.0008) and adenocarcinoma ( P = 0.01) but not in mesothelioma, compared to IV drug application alone. In minipigs, intrapleural photo‐induction combined to systemic Lipoplatin® was well tolerated with no toxicity at 7 days for both treatment protocols. The pleural Lipoplatin® concentrations were not significantly different at 10 and 30 J/cm 2 locations but they were significantly higher in protocol I compared to II (2.37 ± 0.7 vs. 1.37 ± 0.7 ng/mg, P < 0.001). Conclusion Visudyne®‐mediated photo‐induction selectively enhances the uptake of IV administered Lipoplatin® in rodent lung tumors. Intrapleural VATS photo‐induction with identical treatment conditions combined to IV Lipoplatin chemotherapy is feasible and well tolerated in a porcine model. Lasers Surg. Med. 47:807–816, 2015. © 2015 Wiley Periodicals, Inc.