Phase II study of a liposome-entrapped cisplatin analog (L-NDDP) administered intrapleurally and pathologic response rates in patients with malignant pleural mesothelioma

Charles Lu, Roman Perez-Soler, Bilal Piperdi, Garrett L. Walsh, Stephen G. Swisher, W. Roy Smythe, Hyung J. Shin, Jae Y. Ro, Lei Feng, Mylene Truong, Adiseshu Yalamanchili, Gabriel Lopez-Berestein, Waun K. Hong, Abdul R. Khokhar, Dong M. Shin

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Abstract

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.

Original languageEnglish (US)
Pages (from-to)3495-3501
Number of pages7
JournalJournal of Clinical Oncology
Volume23
Issue number15
DOIs
StatePublished - 2005
Externally publishedYes

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Liposomes
Cisplatin
Biopsy
Communication
Therapeutics
bis-neodecanoato-1,2-diaminocyclohexaneplatinum(II)
Ac-Nal(1)-Cpa(2)-Pal(3,6)-Arg(5)-Ala(10)-lHRH
Malignant Mesothelioma
Thoracoscopy
Empyema
Cellulitis
Mesothelioma
Residual Neoplasm
Anorexia
Pleural Effusion
Neutropenia
Peritonitis
Dyspnea
Anemia
Fever

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Phase II study of a liposome-entrapped cisplatin analog (L-NDDP) administered intrapleurally and pathologic response rates in patients with malignant pleural mesothelioma. / Lu, Charles; Perez-Soler, Roman; Piperdi, Bilal; Walsh, Garrett L.; Swisher, Stephen G.; Smythe, W. Roy; Shin, Hyung J.; Ro, Jae Y.; Feng, Lei; Truong, Mylene; Yalamanchili, Adiseshu; Lopez-Berestein, Gabriel; Hong, Waun K.; Khokhar, Abdul R.; Shin, Dong M.

In: Journal of Clinical Oncology, Vol. 23, No. 15, 2005, p. 3495-3501.

Research output: Contribution to journalArticle

Lu, C, Perez-Soler, R, Piperdi, B, Walsh, GL, Swisher, SG, Smythe, WR, Shin, HJ, Ro, JY, Feng, L, Truong, M, Yalamanchili, A, Lopez-Berestein, G, Hong, WK, Khokhar, AR & Shin, DM 2005, 'Phase II study of a liposome-entrapped cisplatin analog (L-NDDP) administered intrapleurally and pathologic response rates in patients with malignant pleural mesothelioma', Journal of Clinical Oncology, vol. 23, no. 15, pp. 3495-3501. https://doi.org/10.1200/JCO.2005.00.802
Lu, Charles ; Perez-Soler, Roman ; Piperdi, Bilal ; Walsh, Garrett L. ; Swisher, Stephen G. ; Smythe, W. Roy ; Shin, Hyung J. ; Ro, Jae Y. ; Feng, Lei ; Truong, Mylene ; Yalamanchili, Adiseshu ; Lopez-Berestein, Gabriel ; Hong, Waun K. ; Khokhar, Abdul R. ; Shin, Dong M. / Phase II study of a liposome-entrapped cisplatin analog (L-NDDP) administered intrapleurally and pathologic response rates in patients with malignant pleural mesothelioma. In: Journal of Clinical Oncology. 2005 ; Vol. 23, No. 15. pp. 3495-3501.
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abstract = "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.",
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T1 - Phase II study of a liposome-entrapped cisplatin analog (L-NDDP) administered intrapleurally and pathologic response rates in patients with malignant pleural mesothelioma

AU - Lu, Charles

AU - Perez-Soler, Roman

AU - Piperdi, Bilal

AU - Walsh, Garrett L.

AU - Swisher, Stephen G.

AU - Smythe, W. Roy

AU - Shin, Hyung J.

AU - Ro, Jae Y.

AU - Feng, Lei

AU - Truong, Mylene

AU - Yalamanchili, Adiseshu

AU - Lopez-Berestein, Gabriel

AU - Hong, Waun K.

AU - Khokhar, Abdul R.

AU - Shin, Dong M.

PY - 2005

Y1 - 2005

N2 - 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.

AB - 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.

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