Intracavitary cisplatin-fibrin chemotherapy after surgery for malignant pleural mesothelioma: A phase I trial.

Abstract

OBJECTIVES:

Intracavitary chemotherapy is a promising concept to improve local tumor control for malignant pleural mesothelioma with reported high morbidity rates. We have demonstrated that administration of cisplatin loaded to fibrin increased local drug concentration and reduced systemic toxicity in preclinical models. We present a phase I trial of intracavitary cisplatin-fibrin after surgical tumor resection.

METHODS:

A total of 12 patients (75% International Mesothelioma Interest Group stage III-IV) were treated with 4 dose levels of intracavitary cisplatin-fibrin (11-44 mg/m2 body surface area) in a dose-escalating design. Cisplatin-fibrin was sprayed on the resected surfaces after pleurectomy/decortication. Blood and tissue samples were taken to assess toxicity and pharmacokinetics. Patients were regularly followed up.

RESULTS:

No dose-limiting toxicity was observed. Major morbidity occurred in 4 patients (33%). The 30-day and 90-day mortality were both 0%. Of 80 adverse events, 9 were classified serious, but none of these were related to study treatment. Local cisplatin concentration in the chest wall tissue was high at all dose levels (median, 46.3 μg/g [12-133 μg/g]). In serum, median cisplatin area under the concentration time curve values were always below renal toxicity levels. The median overall survival with 95% confidence interval was 21 months (10-31 months). In 1 patient with epithelioid malignant pleural mesothelioma (International Mesothelioma Interest Group stage I), there was no sign of relapse 48 months after treatment (44 mg/m2 body surface area).

CONCLUSIONS:

The administration of intracavitary cisplatin-fibrin is safe with favorable pharmacokinetics. Although most patients had advanced disease, long-term outcomes are comparable to other multimodal concepts. A confirmation phase II trial is ongoing.

• Authors: Isabelle Opitz, Olivia Lauk, Mayura Meerang, Alexander Jetter, Beat Aeschlimann, Burkhardt Seifert, Detlef Günther, Rolf A Stahel, Walter Weder
• Journal: The Journal of thoracic and cardiovascular surgery (J Thorac Cardiovasc Surg) Vol. 159 Issue 1 Pg. 330-340.e4 (Jan 2020) ISSN: 1097-685X [Electronic] United States
• PMID: 31590949 (Publication Type: Journal Article)
• Copyright: Copyright © 2019 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.