Toxicity of hyperthermic intraperitoneal chemotherapy (HIPEC) in pediatric patients with sarcomatosis/carcinomatosis: Early experience and phase 1 results

Abstract

Intra-abdominal metastasis is a rare form of tumor dissemination in children. Complete surgical resection is usually deemed impossible. Children are frequently offered palliative care only. We adopted an aggressive approach for these cases which includes removal of dozens to hundreds of tumor nodules followed by perfusion of the abdominal cavity with hyperthermic chemotherapy (HIPEC) with a curative intent. We evaluated toxicity in 23 children and young adults undergoing 27 HIPEC procedures using cisplatin. Disease diagnoses included rhabdomyosarcoma (RMS), non-RMS soft tissue sarcoma, (NRSTS), desmoplastic small round cell tumor, (DSRCT), mesothelioma, Wilms tumor, melanomatosis, and adenocarcinoma. Patients underwent cytoreductive surgery followed by cisplatin at 40.5-41 °C, for 90 minutes. A subset of these patients was enrolled on our phase 1 study and as part of dose escalation cohort received 150 mg/m(2) of cisplatin. All toxicities were recorded. Maximum tolerated dose was 100 mg/m(2). Dose limiting toxicity was grade 3 renal failure. In five of 27, 18% had grade 3 or higher renal failure. One patient developed a subclinical decrease in hearing and there were 2 grade 3 hematologic toxicities, 2 grade 3 hepatic toxicities, and one grade 3 ileus. One patient suffered grade3 cardiotoxicity. There were no operative/perioperative mortalities. Surgical complications occurred in 5/27 (18%) of patients. With a follow-up of 6-60 months, seven patients (26%) had no recurrence. HIPEC is reasonably tolerated in pediatric patients with extensive abdominal metastasis. More study is needed to determine for which histologies HIPEC is most efficacious.