title: Phase II study of a liposome-entrapped cisplatin analog (L-NDDP) administered intrapleurally and pathologic response rates in patients with malignant pleural mesothelioma.
abstract: OBJECTIVE
  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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Thoracic/Head & Neck Medical Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, TX, USA.
authors.forename: Charles
authors.initials: C
authors.lastname: Lu
authors.forename: Roman
authors.initials: R
authors.lastname: Perez-Soler
authors.forename: Bilal
authors.initials: B
authors.lastname: Piperdi
authors.forename: Garrett L
authors.initials: GL
authors.lastname: Walsh
authors.forename: Stephen G
authors.initials: SG
authors.lastname: Swisher
authors.forename: W Roy
authors.initials: WR
authors.lastname: Smythe
authors.forename: Hyung J
authors.initials: HJ
authors.lastname: Shin
authors.forename: Jae Y
authors.initials: JY
authors.lastname: Ro
authors.forename: Lei
authors.initials: L
authors.lastname: Feng
authors.forename: Mylene
authors.initials: M
authors.lastname: Truong
authors.forename: Adiseshu
authors.initials: A
authors.lastname: Yalamanchili
authors.forename: Gabriel
authors.initials: G
authors.lastname: Lopez-Berestein
authors.forename: Waun K
authors.initials: WK
authors.lastname: Hong
authors.forename: Abdul R
authors.initials: AR
authors.lastname: Khokhar
authors.forename: Dong M
authors.initials: DM
authors.lastname: Shin
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001707:Biopsy, Needle; D010478:Chemotherapy, Cancer, Regional Perfusion; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004337:Drug Carriers; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007150:Immunohistochemistry; D008081:Liposomes; D008297:Male; D008654:Mesothelioma / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology* / Q000601:surgery; D008875:Middle Aged; D009367:Neoplasm Staging; D009944:Organoplatinum Compounds / Q000008:administration & dosage* / Q000009:adverse effects; D010997:Pleural Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology* / Q000601:surgery; D011336:Probability; D018570:Risk Assessment; D015996:Survival Rate; D013906:Thoracoscopy; D016896:Treatment Outcome
chemical_list: D004337:Drug Carriers; D008081:Liposomes; D009944:Organoplatinum Compounds; C054367:bis-neodecanoato-1,2-diaminocyclohexaneplatinum(II)