A phase I study of extrapleural pneumonectomy and intracavitary intraoperative hyperthermic cisplatin with amifostine cytoprotection for malignant pleural mesothelioma.
OBJECTIVE
This study was undertaken to determine maximum tolerated dose and toxicity of intraoperative intracavitary hyperthermic cisplatin perfusion with amifostine after extrapleural pneumonectomy for malignant pleural mesothelioma.


METHODS
Patients with mesothelioma were prospectively enrolled. Those with resectable disease received amifostine and 1-hour hyperthermic cisplatin perfusion of ipsilateral hemithorax and abdomen. Morbidity, recurrence, and survival were recorded.


RESULTS
Forty-two patients were enrolled; 29 underwent resection (operative mortality 7%, 2/29). Median age was 57 years. Eighteen were in pathologic stage I or II; 11 were in stage III. Median hospitalization was 15 days. Common complications were atrial fibrillation (66%, 19 patients), deep venous thrombosis (31%, 9 patients), and grade 3+ renal toxicity (31%, 9 patients). Feasibility was determined. Renal toxicity was unrelated to cisplatin dose, with no maximum tolerated dose determined. Overall median survival was 17 months (resected 20 months, unresected 10 months). Median survivals were 26 months for patients receiving higher cisplatin doses and 16 months for those receiving lower doses (P = .35). Survival was significantly longer with negative extrapleural nodes (31 vs 14 months, P = .0115) and early stage (all resected 35 months for stage I-II vs 14 months for stage III, P = .0022, epithelial 39 months for stage I-II vs 15 months for stage III, P = .0072).


CONCLUSIONS
Early stage and negative extrapleural lymph nodes were associated with prolonged survival. Single-dose amifostine did not protect adequately against cisplatin-induced renal toxicity. Additional cytoprotective strategies are needed to allow determination of cisplatin maximum tolerated dose.
Zellos
Lambros
L
Division of Thoracic Surgery and Department of Pathology, Brigham and Women's Hospital, Boston, Mass, USA.
Richards
William G
WG
Capalbo
Leah
L
Jaklitsch
Michael T
MT
Chirieac
Lucian R
LR
Johnson
Bruce E
BE
Bueno
Raphael
R
Sugarbaker
David J
DJ
D004999:Amifostine / Q000008:administration & dosage*; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D002945:Cisplatin / Q000008:administration & dosage*; D019610:Cytoprotection; D005240:Feasibility Studies; D005260:Female; D006801:Humans; D006979:Hyperthermia, Induced; D007432:Intraoperative Period; D008297:Male; D020714:Maximum Tolerated Dose; D008654:Mesothelioma / Q000401:mortality / Q000473:pathology / Q000601:surgery*; D008875:Middle Aged; D009367:Neoplasm Staging; D010997:Pleural Neoplasms / Q000401:mortality / Q000473:pathology / Q000601:surgery*; D011013:Pneumonectomy; D011837:Radiation-Protective Agents / Q000008:administration & dosage*; D016019:Survival Analysis
D000970:Antineoplastic Agents; D011837:Radiation-Protective Agents; D004999:Amifostine; D002945:Cisplatin