Boyer M W, Moertel C L, Priest J R, Woods W G
Department of Pediatrics, University of Minnesota, Minneapolis.
J Clin Oncol. 1995 Mar;13(3):631-6. doi: 10.1200/JCO.1995.13.3.631.
Intracavitary (IC) delivery of cisplatin (CDDP) has been used in the treatment of a variety of adult malignancies based on the favorable pharmacokinetics obtained locally. Since IC CDDP has not been reported in children, we studied its use in a group of pediatric patients with regard to safety, toxicity, pharmacokinetics, and responses.
Eleven patients with an age range of 8 months to 21 years with diagnoses of rhabdomyosarcoma (n = 5), pleuropulmonary blastoma (n = 2), osteosarcoma (n = 2), Ewing's sarcoma (n = 1), and malignant rhabdoid tumor of the kidney (n = 1) were studied. Eight patients received intrapleural (IPL) CDDP and three received intraperitoneal (IP) CDDP, either at diagnosis (n = 3) or relapse (n = 8), for malignant pleural effusion (n = 3), malignant ascites (n = 2), pleural-based tumor (n = 4), pulmonary metastases (n = 1), or abdominal tumor spillage (n = 1).
IC CDDP was well tolerated by pediatric patients. Two patients experienced a transient increase in serum creatinine levels (> two times baseline) and two patients experienced severe neutropenia (absolute neutrophil count < 500/microL). Pharmacokinectic measurements showed a 40-fold advantage for the pleural cavity versus serum after IPL CDDP and serum levels comparable to those achieved with systemic administration of CDDP. Four of five patients who received IC CDDP for malignant ascites or pleural effusion had at least a temporary response. Only three of 11 patients studied had local recurrences following IC CDDP. There are currently four survivors in the study group, including two long-term survivors at greater than 8 years since IPL CDDP treatment.
The safety, toxicity, and pharmacokinetics of IC CDDP in pediatric patients are similar to that reported in adult patients. The low incidence of local recurrence following IC CDDP in this group of largely relapsed patients suggests that further study of IC CDDP for pediatric patients is warranted.
基于局部获得的良好药代动力学，顺铂（CDDP）腔内（IC）给药已用于治疗多种成人恶性肿瘤。由于儿童中尚未有IC CDDP的相关报道，我们研究了其在一组儿科患者中的安全性、毒性、药代动力学及反应情况。
研究了11例年龄范围为8个月至21岁的患者，诊断包括横纹肌肉瘤（n = 5）、胸膜肺母细胞瘤（n = 2）、骨肉瘤（n = 2）、尤因肉瘤（n = 1）和肾恶性横纹肌样瘤（n = 1）。8例患者接受胸腔内（IPL）CDDP治疗，3例接受腹腔内（IP）CDDP治疗，于诊断时（n = 3）或复发时（n = 8）进行，用于治疗恶性胸腔积液（n = 3）、恶性腹水（n = 2）、胸膜肿瘤（n = 4）、肺转移瘤（n = 1）或腹部肿瘤外溢（n = 1）。
儿科患者对IC CDDP耐受性良好。2例患者血清肌酐水平短暂升高（>基线的两倍），2例患者出现严重中性粒细胞减少（绝对中性粒细胞计数<500/μL）。药代动力学测量显示，IPL CDDP后胸腔与血清的比值有40倍优势，且血清水平与全身给予CDDP时相当。接受IC CDDP治疗恶性腹水或胸腔积液的5例患者中有4例至少有暂时反应。研究的11例患者中只有3例在IC CDDP后出现局部复发。研究组目前有4名幸存者，包括2名自IPL CDDP治疗后存活超过8年的长期幸存者。
儿科患者中IC CDDP的安全性、毒性和药代动力学与成人患者报道的相似。在这组大多为复发患者中，IC CDDP后局部复发的发生率较低，提示有必要对儿科患者的IC CDDP进行进一步研究。
