Navigation auf zora.uzh.ch

Search ZORA

ZORA (Zurich Open Repository and Archive)

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

Opitz, Isabelle; Lauk, Olivia; Meerang, Mayura; Jetter, Alexander; Aeschlimann, Beat; Seifert, Burkhardt; Günther, Detlef; Stahel, Rolf A; Weder, Walter (2020). Intracavitary cisplatin-fibrin chemotherapy after surgery for malignant pleural mesothelioma: A phase I trial. Journal of Thoracic and Cardiovascular Surgery, 159(1):330-340.e4.

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/m$^{2}$ 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/m$^{2}$ 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.

Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Clinic for Oncology and Hematology
04 Faculty of Medicine > Epidemiology, Biostatistics and Prevention Institute (EBPI)
04 Faculty of Medicine > University Hospital Zurich > Clinic for Clinical Pharmacology and Toxicology
04 Faculty of Medicine > University Hospital Zurich > Clinic for Thoracic Surgery
Dewey Decimal Classification:610 Medicine & health
Scopus Subject Areas:Health Sciences > Surgery
Health Sciences > Pulmonary and Respiratory Medicine
Health Sciences > Cardiology and Cardiovascular Medicine
Language:English
Date:1 January 2020
Deposited On:05 Dec 2019 11:02
Last Modified:22 Oct 2024 01:38
Publisher:Elsevier
ISSN:0022-5223
OA Status:Closed
Publisher DOI:https://doi.org/10.1016/j.jtcvs.2019.07.073
PubMed ID:31590949
Full text not available from this repository.

Metadata Export

Statistics

Citations

Dimensions.ai Metrics
15 citations in Web of Science®
16 citations in Scopus®
Google Scholar™

Altmetrics

Authors, Affiliations, Collaborations

Similar Publications