Abstract | OBJECTIVE: METHODS: An orthotopic rat recurrence model of malignant pleural mesothelioma was used. Five animals per group were evaluated. Polymeric films (4.5 cm diameter) for the local delivery of anticancer drug were constructed: hyaluronate, chitosan and the combined dual-layer polymers were loaded with cisplatin at a concentration of 100 mgm(-2). Animals without any adjuvant therapy were used as control. Mesothelioma cells were injected subpleurally in the anaesthetised rats. Six days later, a pleural tumour of 5.5mm was resected and a left pneumonectomy and pleural abrasion were performed. Thereafter, the cisplatin-loaded and unloaded films or cisplatin solution were intrapleurally applied, according to randomisation. After 6 days, animals were euthanised and organs harvested for morphological and histological evaluations. The primary endpoint was the volume of tumour recurrence. The secondary endpoints were treatment-related toxicity; cisplatin serum concentration evaluated at different time points; and cisplatin concentration in the pleura measured at autopsy. Analysis of variance (ANOVA) was used for statistical analysis. Bonferroni correction was applied for comparison between all groups. RESULTS: Tumour volume was significantly reduced in the hyaluronate cisplatin and hyaluronate- chitosan cisplatin groups in comparison to control groups (p=0.001 and p<0.0001, respectively). Animals treated with hyaluronate- chitosan cisplatin had a tumour recurrence significantly lesser than animals treated with cisplatin solution (p=0.003) and hyaluronate cisplatin (p=0.032). No toxicity related to the different treatments was observed. On postoperative days 1 and 2, cisplatin was detected in the serum at a concentration six- and sevenfold significantly higher in the hyaluronate cisplatin and hyaluronate- chitosan cisplatin groups, in comparison to cisplatin solution, and was maintained over time. Cisplatin levels in the pleura were higher in the hyaluronate- chitosan cisplatin group than in all others. CONCLUSIONS:
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Authors | Luca Ampollini, Fabio Sonvico, Elisabetta Barocelli, Andrea Cavazzoni, Rocco Bilancia, Claudio Mucchino, Anna Maria Cantoni, Paolo Carbognani |
Journal | European journal of cardio-thoracic surgery : official journal of the European Association for Cardio-thoracic Surgery
(Eur J Cardiothorac Surg)
Vol. 37
Issue 3
Pg. 557-65
(Mar 2010)
ISSN: 1873-734X [Electronic] Germany |
PMID | 19766508
(Publication Type: Journal Article)
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Copyright | Copyright (c) 2009 European Association for Cardio-Thoracic Surgery. Published by Elsevier B.V. All rights reserved. |
Chemical References |
- Antineoplastic Agents
- Pharmaceutical Vehicles
- Polymers
- Hyaluronic Acid
- Chitosan
- Cisplatin
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Topics |
- Animals
- Antineoplastic Agents
(administration & dosage, pharmacokinetics)
- Chemotherapy, Adjuvant
(methods)
- Chitosan
- Cisplatin
(administration & dosage, pharmacokinetics)
- Hyaluronic Acid
- Male
- Mesothelioma
(metabolism, pathology, prevention & control, surgery)
- Neoplasm Recurrence, Local
(prevention & control)
- Pharmaceutical Vehicles
(administration & dosage, pharmacokinetics)
- Pleural Neoplasms
(metabolism, pathology, prevention & control, surgery)
- Pneumonectomy
(methods)
- Polymers
- Rats
- Rats, Inbred F344
- Xenograft Model Antitumor Assays
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