Richards William G, Zellos Lambros, Bueno Raphael, Jaklitsch Michael T, Jänne Pasi A, Chirieac Lucian R, Yeap Beow Y, Dekkers Rene J, Hartigan Phillip M, Capalbo Leah, Sugarbaker David J
Brigham and Women's Hospital, Boston, MA 02115, USA.
J Clin Oncol. 2006 Apr 1;24(10):1561-7. doi: 10.1200/JCO.2005.04.6813.
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).
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.
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.
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.
评估接受恶性胸膜间皮瘤（MPM）胸膜切除术的患者术中腔内高温顺铂灌洗的发病率、死亡率、最大耐受剂量（MTD）及预后。
前瞻性登记61例患者。44例可切除的MPM患者接受胸膜切除术，随后在42℃用剂量递增的顺铂（50、100、150、175、200、225和250mg/m²）对切除腔进行1小时灌洗，然后静脉注射硫代硫酸钠（6小时内16g/m²）。使用对数秩检验和比例风险回归比较生存估计值。
中位年龄为71岁（范围50至82岁）。24例患者为上皮性肿瘤，20例为肉瘤样或混合组织学类型。术后死亡率为11%（44例患者中的5例）。250mg/m²时出现剂量限制性肾毒性，确定MTD为225mg/m²。其他并发症包括心房颤动（44例患者中的14例，32%）和深静脉血栓形成（44例患者中的4例，9%）。所有登记患者的中位生存时间为9个月，切除患者的中位生存时间为13个月。接受低剂量（50至150mg/m²；n = 9；中位值6个月）与高剂量（175至250mg/m²；n = 35；中位值18个月）高温顺铂灌洗的可切除患者的生存估计值有显著差异（P = 0.0019）；无复发生存期也有显著差异（分别为4个月和9个月；P < 0.0001）。低剂量水平（相对风险 = 3.418）和非上皮组织学类型（相对风险 = 2.336）是生存不良的独立危险因素。20例接受高剂量顺铂灌洗的上皮性肿瘤患者的中位生存时间为2年6个月。
对于手术选择受限的该类患者群体，胸膜切除术及术中高剂量腔内高温顺铂灌洗是可行的。明显的剂量相关生存获益值得进一步研究。
