A phase I trial of continuous hyperthermic peritoneal perfusion using cisplatin in pediatric patients with carcinomatosis.

Abstract

9544 Background: The delivery of regional hyperthermic chemotherapy using continuous hyperthermic peritoneal perfusion (CHPP) has been well established in adults with carcinomatosis. This approach has not previously been used in children. Here we report a phase I trial of CHPP using cisplatin after extensive cytoreductive surgery for pediatric patients with extensive abdominal metastasis from sarcomatosis or mesothelioma. Methods: This phase I study includes 10 enrollments in patients age 3 to 18 years who received dose escalation of cisplatin after cytoreductive surgery followed by CHPP at a single institution. A standard 3 by 3 dose escalation format was used starting at 100 mg/m2. Patients diagnosed with desmoplastic small round cell tumor (DSRCT), rhabdomyosarcoma (RMS), liposarcoma and mesothelioma who had refractory and extensive abdominal disease were included. Patients with liver metastasis were included. However, patients with disease outside of the abdominal cavity were excluded. A summary of morbidities and toxicities including dose limiting toxicity (DLT) and maximum tolerated dose (MTD) are reported. Results: All subjects enrolled completed the study and there were no on study mortalities. DLT was renal insufficiency manifest as elevation in creatinine without the need for dialysis. MTD was 150 mg/m2 given for 90 minutes at 40.5 degrees Celsius. There were 2 grade 3 renal toxicities, 2 grade 3 hematologic toxicities, 2 grade 3 hepatic toxicities and one grade 3 ileus. There was one grade 3 cardiomyopathy, asymptomatic and resolved with Beta blockers and one grade 4 wound complication. Number of tumor implants removed prior to hyperthermic perfusion with cisplatin ranged from 5 to 402 including splenectomy, partial diaphragm resection, bowel resection, cholecystectomy and partial peritonectomy. Hospital stay ranged from 5 to 13 days. Forty percent of patients had progressive disease (PD) and 60% had a complete response (CR) for at least 6 months. Conclusions: CHPP using cisplatin is safe in children at a dose of 100 mg/m2 at 40.5 degrees Celsius for 90 minutes. Renal insufficiency is likely at doses at, or greater than150 mg/m2. No significant financial relationships to disclose.