Toxicity and outcomes associated with surgical cytoreduction and hyperthermic intraperitoneal chemotherapy (HIPEC) for patients with sarcomatosis

Background: Treatment of peritoneal recurrence following surgical resection of intra-abdominal sarcomas presents a significant challenge to clinicians. Historically, treatment with systemic chemotherapy has been ineffective and surgical resection alone has not been durable. We prospectively evaluated the feasibility of cytoreductive surgery followed by hyperthermic intraperitoneal chemotherapy (HIPEC) with cisplatin (CDDP) alone or in combination with mitoxantrone (MITOX) for the treatment of sarcomatosis. Methods: Two phase I trials of HIPEC were conducted (1998-2003). Eligible patients with evidence of sarcomatosis underwent cytoreductive surgery followed by HIPEC. In the first trial, CDDP dosing was established as 90 mg/m² with a perfusate time of 90 minutes and temperature of 41°C. In the second trial, MITOX (20 mg/m²) was instilled following perfusion with CDDP. Toxicity, efficacy, and quality of life (QOL) were evaluated. Results: A total of 28 patients were enrolled in the two trials. We noted a higher overall toxicity score and complication rate with combination CDDP/MITOX versus CDDP alone and shorter overall survival duration (5.5 months vs 16.9 months, respectively). In addition, local recurrence rates were similar in both groups (CDDP 79% vs CDDP/MITOX 68%). As expected, QOL scores at 6-8 weeks following HIPEC were 15-25% lower than the baseline scores; however, they returned to baseline at 3-6 months. Conclusions: Although the HIPEC technique is feasible for patients with sarcomatosis, it is associated with significant toxicity and limited clinical benefit. Combination CDDP/MITOX failed to demonstrate any benefit over CDDP alone; moreover, there was an increase in toxicity.