Online citations, reference lists, and bibliographies.
← Back to Search

Intracavitary Cisplatin-fibrin Chemotherapy After Surgery For Malignant Pleural Mesothelioma: A Phase I Trial.

I. Opitz, O. Lauk, Mayura Meerang, A. Jetter, B. Aeschlimann, B. Seifert, D. Guenther, R. Stahel, W. Weder
Published 2019 · Medicine

Cite This
Download PDF
Analyze on Scholarcy
Share
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.
This paper references
10.1056/NEJM198710223171717
Simplified Calculation of Body-Surface Area
Mosteller Rd (1987)
10.1093/icvts/ivw422
Propensity matched comparison of extrapleural pneumonectomy and pleurectomy/decortication for mesothelioma patients.
Arthur Kostron (2017)
10.1016/j.jtcvs.2010.09.032
Optimized intrapleural cisplatin chemotherapy with a fibrin carrier after extrapleural pneumonectomy: a preclinical study.
I. Opitz (2011)
10.1016/j.jtcvs.2008.02.079
Autologous fibrin sealant reduces the incidence of prolonged air leak and duration of chest tube drainage after lung volume reduction surgery: a prospective randomized blinded study.
C. Moser (2008)
10.1517/14712598.2014.897323
Fibrin sealants: surgical hemostat, sealant and adhesive
S. Mandell (2014)
10.1007/s00280-007-0500-1
Preclinical studies of the proteasome inhibitor bortezomib in malignant pleural mesothelioma
G. Gordon (2007)
10.1016/S0022-5223(99)70297-7
Pleural space perfusion with cisplatin in the multimodality treatment of malignant mesothelioma: a feasibility and pharmacokinetic study.
G. B. Ratto (1999)
10.1200/JCO.2005.04.6813
Phase I to II study of pleurectomy/decortication and intraoperative intracavitary hyperthermic cisplatin lavage for mesothelioma.
W. Richards (2006)
10.1016/j.jtcvs.2009.02.046
Extrapleural pneumonectomy followed by intracavitary intraoperative hyperthermic cisplatin with pharmacologic cytoprotection for treatment of malignant pleural mesothelioma: a phase II prospective study.
T. R. Tilleman (2009)
10.1093/ANNONC/MDM093
Multicenter trial of neo-adjuvant chemotherapy followed by extrapleural pneumonectomy in malignant pleural mesothelioma.
W. Weder (2007)
10.1016/j.jtcvs.2012.12.037
Hyperthermic intraoperative pleural cisplatin chemotherapy extends interval to recurrence and survival among low-risk patients with malignant pleural mesothelioma undergoing surgical macroscopic complete resection.
D. Sugarbaker (2013)
10.1378/CHEST.121.2.480
Cytoreductive surgery and intraoperative hyperthermic intrathoracic chemotherapy in patients with malignant pleural mesothelioma or pleural metastases of thymoma.
E. de Bree (2002)
10.1023/A:1015939917646
Estimation of Bioavailability on a Single Occasion After Semisimultaneous Drug Administration
M. Karlsson (2004)
10.1016/J.JTCVS.2005.08.012
Intrapleural topical application of cisplatin with the surgical carrier Vivostat increases the local drug concentration in an immune-competent rat model with malignant pleuromesothelioma.
D. Lardinois (2006)
10.1016/j.lungcan.2013.11.026
A systematic review and meta-analysis of surgical treatments for malignant pleural mesothelioma.
C. Cao (2014)
10.1177/030089169608200111
Surgery Followed by Intracavitary plus Systemic Chemotherapy in Malignant Pleural Mesothelioma
M. Colleoni (1996)
10.1097/JTO.0b013e3181ae25bf
Outcome for Patients with Malignant Pleural Mesothelioma Referred for Trimodality Therapy in Western Australia
A. Hasani (2009)
10.1007/s00280-007-0484-x
Improvement in intraperitoneal intraoperative cisplatin exposure based on pharmacokinetic analysis in patients with ovarian cancer
B. Royer (2007)
10.1155/2012/471205
Pharmacokinetics of Hyperthermic Intrathoracic Chemotherapy following Pleurectomy and Decortication
P. Sugarbaker (2012)
10.1200/JCO.2017.76.6394
Treatment of Malignant Pleural Mesothelioma: American Society of Clinical Oncology Clinical Practice Guideline.
H. Kindler (2018)
10.1016/S0003-2670(01)01041-8
Trace analysis of platinum in biological samples: a comparison between sector field ICP-MS and adsorptive cathodic stripping voltammetry following different digestion procedures
S. Zimmermann (2001)
10.1007/s10637-009-9317-6
Justification of the starting dose as the main determinant of accrual time in dose-seeking oncology phase 1 trials
N. Penel (2009)
10.2165/11317280-000000000-00000
Population Pharmacokinetics and Dosing Recommendations for Cisplatin during Intraperitoneal Peroperative Administration
H. Ehrsson (2009)
10.1186/1477-7819-7-14
Intra-operative intra-peritoneal chemotherapy with cisplatin in patients with peritoneal carcinomatosis of ovarian cancer
E. Guardiola (2009)
10.1200/JCO.2008.17.5604
Trimodality therapy with induction chemotherapy followed by extrapleural pneumonectomy and adjuvant high-dose hemithoracic radiation for malignant pleural mesothelioma.
M. D. de Perrot (2009)
10.1093/ejcts/ezs418
Cytoreductive surgery and hyperthermic intrathoracic chemotherapy perfusion for malignant pleural tumours: perioperative management and clinical experience.
M. Ried (2013)
10.1016/J.EJCTS.2007.01.047
Local recurrence model of malignant pleural mesothelioma for investigation of intrapleural treatment.
I. Opitz (2007)
Pleurectomy/decortication plus chemotherapy: outcomes of 40 cases of malignant pleural mesothelioma.
F. Colaut (2004)
10.1016/0003-4975(94)91066-9
Aggressive multimodality therapy for malignant pleural mesothelioma.
T. Rice (1994)
10.1200/JCO.1994.12.6.1156
A phase II trial of pleurectomy/decortication followed by intrapleural and systemic chemotherapy for malignant pleural mesothelioma.
V. Rusch (1994)
10.1016/S1547-4127(04)00109-4
Innovative therapies: intraoperative intracavitary chemotherapy.
M. Chang (2004)
10.1200/JCO.2008.20.3943
Multicenter phase II trial of neoadjuvant pemetrexed plus cisplatin followed by extrapleural pneumonectomy and radiation for malignant pleural mesothelioma.
L. Krug (2009)
10.1245/ASO.2003.03.022
Cytoreductive Surgery Combined With Intraoperative Hyperthermic Intrathoracic Chemotherapy for Stage I Malignant Pleural Mesothelioma
S. van Ruth (2003)
10.1016/j.jtcvs.2008.07.055
A phase I study of extrapleural pneumonectomy and intracavitary intraoperative hyperthermic cisplatin with amifostine cytoprotection for malignant pleural mesothelioma.
L. Zellos (2009)
10.1200/JCO.1992.10.6.1001
Intrapleural cisplatin and mitomycin for malignant mesothelioma following pleurectomy: pharmacokinetic studies.
V. Rusch (1992)
10.1007/s00228-001-0405-6
Estimating the starting dose for entry into humans: principles and practice
B. Reigner (2001)
10.3892/IJO_00000692
Putative cancer stem cells in malignant pleural mesothelioma show resistance to cisplatin and pemetrexed.
L. Cortes-Dericks (2010)



This paper is referenced by
Semantic Scholar Logo Some data provided by SemanticScholar