mesothelioma
study
mesothelioma study
study of pleurectomy/decortication and intraoperative intracavitary
hyperthermic cisplatin lavage for mesothelioma.
Richards WG, Zellos L, Bueno R, Jaklitsch MT, Janne PA, Chirieac LR, Yeap
BY, Dekkers RJ, Hartigan PM, Capalbo L, Sugarbaker DJ.
Brigham and Women's Hospital, Boston, MA 02115, USA.
PURPOSE: 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).
PATIENTS AND 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.