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Phase II Study of a Liposome-Entrapped Cisplatin Analog (L-NDDP) Administered Intrapleurally and Pathologic Response Rates in Patients With Malignant Pleural Mesothelioma

From the Departments of Thoracic/Head & Neck Medical Oncology, Thoracic and Cardiovascular Surgery, Pathology, Bioimmunotherapy, Experimental Therapeutics, Diagnostic Radiology and Biostatistics, The University of Texas M.D. Anderson Cancer Center, Houston, TX, and New York University, New York, NY

Address reprint requests to Dong M. Shin, MD, Winship Cancer Institute, Emory University School of Medicine, 1365-C Clifton Rd, Room 3090, Atlanta, GA 30322; e-mail: dong_shin{at}emoryhealthcare.org

PURPOSE: To determine pathologic response rates to liposome-entrapped cis-bisneodecanoato-trans-R,R-1,2-diaminocyclohexane platinum(II) (L-NDDP) administered intrapleurally in patients with malignant pleural mesothelioma.

PATIENTS AND METHODS: Thirty-three patients with malignant pleural mesothelioma and free-flowing pleural effusions received intrapleural L-NDDP once every 3 weeks at a dose of 450 mg/m². Thoracoscopic evaluation with pleural biopsies was performed before therapy and then after every two cycles. The primary end point was pathologic response as determined by thoracoscopic biopsy.

RESULTS: After at least two cycles, post-treatment pleural biopsy analysis was negative in 14 patients for a pathologic response rate of 42% (95% CI, 25% to 61%). Median survival was 11.2 months. There were three treatment-related deaths secondary to peritonitis, cellulitis at the thoracoscopy site, and empyema. Grade 3 nonhematologic toxicities included infection, fever, dyspnea, and anorexia, which occurred in five (15%), one (3%), one (3%), and one (3%) patients, respectively. There were no grade 4 nonhematologic toxicities. Grade 3 or 4 neutropenia, thrombocytopenia, and anemia occurred in five (15%), three (9%), and two (6%) patients, respectively. Two patients with pathologic responses subsequently underwent pleural decortication. Both surgical specimens revealed residual tumor in regions that were not in direct communication with the pleural space.

CONCLUSION: Intrapleural L-NDDP therapy in this patient population is feasible with significant but manageable toxicity. Although pathologic responses are highly encouraging, areas of mesothelioma that are not in direct communication with the pleural space will evade drug exposure and limit efficacy in some patients. The optimal role of intrapleural L-NDDP therapy currently remains to be determined.

Supported by grant No. K12 CA088084 from the National Cancer Institute (C. L.) and FD-R-00167 from the U.S. Food and Drug Administration Orphan Product Grant (D.M.S.) and Antigenics Inc, New York, NY (formerly Aronex Pharmaceuticals, Houston, TX).

Authors' disclosures of potential conflicts of interest are found at the end of this article.

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