Phase I to II study of pleurectomy/decortication and intraoperative intracavitary hyperthermic cisplatin lavage for mesothelioma.
OBJECTIVE
To evaluate morbidity, mortality, maximum-tolerated dose (MTD), and outcome of intraoperative intracavitary hyperthermic cisplatin lavage in patients undergoing pleurectomy for malignant pleural mesothelioma (MPM).


METHODS
Sixty-one patients were prospectively registered. Forty-four resectable patients with MPM underwent pleurectomy, followed by a 1-hour lavage of the resection cavity with dose-escalated cisplatin (50, 100, 150, 175, 200, 225, and 250 mg/m2) at 42 degrees C and then intravenous sodium thiosulfate (16 g/m2 over 6 hours). Survival estimates were compared using the log-rank test and proportional hazards regression.


RESULTS
Median age was 71 years (range, 50 to 82 years). Twenty-four patients had epithelial tumors, and 20 had sarcomatous or mixed histology. Postoperative mortality was 11% (five of 44 patients). Dose-limiting renal toxicity occurred at 250 mg/m2, establishing the MTD at 225 mg/m2. Other morbidity included atrial fibrillation (14 of 44 patients, 32%) and deep venous thrombosis (four of 44 patients, 9%). Median survival time of all registered patients was 9 months, and the median survival time of resected patients was 13 months. Survival estimates differed significantly for resectable patients exposed to low doses (50 to 150 mg/m2; n = 9; median, 6 months) versus high doses (175 to 250 mg/m2; n = 35; median, 18 months) of hyperthermic cisplatin (P = .0019); recurrence-free interval also differed significantly (4 v 9 months, respectively; P < .0001). Low dose level (relative risk = 3.418) and nonepithelial histology (relative risk = 2.336) were independent risk factors for poor survival. Twenty patients with epithelial tumors who underwent high-dose cisplatin lavage had a 26-month median survival time.


CONCLUSIONS
Pleurectomy and high-dose intraoperative intracavitary hyperthermic cisplatin lavage is feasible in this patient population with restricted surgical options. An apparent dose-related survival benefit warrants further study.
Brigham and Women's Hospital, Boston, MA 02115, USA.
William G
WG
Richards
Lambros
L
Zellos
Raphael
R
Bueno
Michael T
MT
Jaklitsch
Pasi A
PA
Jänne
Lucian R
LR
Chirieac
Beow Y
BY
Yeap
Rene J
RJ
Dekkers
Phillip M
PM
Hartigan
Leah
L
Capalbo
David J
DJ
Sugarbaker
D000368:Aged; D000369:Aged, 80 and over; D002945:Cisplatin / Q000627:therapeutic use*; D003131:Combined Modality Therapy; D005260:Female; D006801:Humans; D006979:Hyperthermia, Induced; D008297:Male; D020714:Maximum Tolerated Dose; D008654:Mesothelioma / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D008875:Middle Aged; D010994:Pleura / Q000601:surgery*; D010997:Pleural Neoplasms / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D011446:Prospective Studies; D017211:Treatment Failure
D002945:Cisplatin