Proffered Papers— Medical Oncology

A PHASE I TRIAL OF INTRAPERITONEAL HYPERTHERMIC CHEMOTHERAPY FOR THE TREATMENT OF SARCOMATOSIS

Bilimoria MM, Feig B, Mansfield P, Pisters PWT, Pollock RE, Patel S, Plager C, Benjamin R, Burgess M, Chase J, Murphy A, Griffin J, Mirza, N, and Hunt K (UT MD Anderson Cancer Center, Houston, TX 77030-4095)

The appropriate therapeutic interventions for patients with intra-abdominal disseminated sarcoma (sarcomatosis) remain unclear. We have previously reported that these patients have a median survival of 13 months irrespective of the current adjuvant therapy available (CTOS abstract #0002, 1999). A phase I study using tumor debulking coupled with hyperthermic peritoneal perfusion with cisplatin was initiated to determine the toxicity, operative complications, and effects on time to tumor progression.

Methods: A total of 25 patients were enrolled in the study of which 19 underwent complete tumor debulking followed by intraperitoneal hyperthermic perfusion with cisplatin. Patients with low volume liver metastases were eligible for perfusion. The dose of cisplatin used was modified from an initial 150 mg/m₂ to 90 mg/m₂. Perfusate time was modified from 120 minutes to 90 minutes. Seventeen patients received a 90 mg/m₂ dose with a perfusion time of 90 minutes. Inlet temperature of perfusate was decreased from 44 to 41 degrees Celsius. All changes were secondary to toxicity.

Results: Two patients were treated with the initial parameters (150 mg/m2 or 120 mg/m2 cisplatin; 44 degrees inlet temperature; 120 minute dwell time). A total of 17 patients were treated with the modified dose of cisplatin (90 mg/m₂), the modified perfusate time (90 minutes), and the modified inlet temperature (41 degrees). The median age of the patients studied was 52 years (range 24-77 years). The median number of separate tumor nodules removed was 100 (range 6-1000+). Median time on mechanical intubation was one day (range 1-39 days) with a median hospital stay of 15 days (range 9-69 days). Median platelet nadir was 85K (range 9-176K) necessitating a median of 0 (range 0-83) platelet transfusions in these patients. The median hemoglobin nadir was 8.2 g/dL (range 7.1-13.4 g/dL) though the median number of perioperative RBC transfusions was 5 units (range 0-34 units). Four patients experienced major complications (24%) in this group. One patient experienced adult respiratory distress syndrome associated with sepsis, another patient experienced pulmonary edema requiring prolonged intubation, and two others experienced renal failure requiring temporary hemodialysis (both patients received an initial dose of cisplatin of 150 mg/m₂ or 120 mg/m₂) . There was one reoperation for postoperative bleeding and there were no perioperative deaths.

Three patients died as a result of metastases to the liver at 7, 11, and 16 months after the procedure. Four patients are alive with no evidence of recurrence 4-8 months following the procedure. The remaining twelve patients are alive with recurrent disease (5 with recurrent peritoneal disease and 7 with primary liver metastases). The median time to local recurrence was 5 months (2-9 months) while the median time to distant recurrence was 4 months (range 1.5-12 months).

Conclusions: This pilot study of tumor debulking and intraperitoneal hyperthermic perfusion with cisplatin in patients with sarcomatosis reveals that the procedure can be performed without mortality and with significant morbidity in only one-quarter of the patients. Although the median time to local recurrence was 5 months, 24% of the patients remain disease-free at a median of 6 months follow-up. All patients who died following the procedure died of metastases to the liver suggesting that although the procedure can control peritoneal disease, patients are still at risk for failure from liver disease. A phase II investigation of this aggressive therapy is needed better define response rates and progression-free in a larger cohort of patients.