Phase I clinical trial of cytoreductive surgery and intraoperative intraperitoneal hyperthermic chemotherapy for the treatment of peritoneal carcinomatosis

Abstract

15633 Background: Peritoneal carcinomatosis (PC) is an end-stage problem gastrointestinal and the pelvic cancers with median survival of less than 6 mon. Cytoreductive surgery (CRS) plus intraoperative peritoneal hyperthermic chemotherapy (IPHC) may improve clinical outcomes in selected pts. This study was to evaluate the safety and efficacy CRS plus IPHC using mitomycin C (MMC) and hydroxycamptothecin (HCPT) in treating PC. Methods: Eligibility criteria were: (1) pts with PC from abdominal or pelvic cancers without evidence of distant metastasis and with expected survival of over 3 mon; (2) 25–70 years old; (3) laboratory workup found no abnomalities limiting aggressive intervention; (4) pts can tolerate big surgery; and (5) written informed consent obtained. 21 pts with PC (12 from gastric cancer, 5 colorectal cancer, 2 ovarian cancer, 1 pseudomyxoma peritonei and 1 malignant mesothelioma) were treated with CRS plus IPHC using HCPT 20 mg and MMC 30 mg in 12,000 ml of normal saline at 43±0.5°C for 60∼90 min. Body temperature and heart rate were recorded for 5 d after operation. Local and systemic infections, gastrointestinal function recovery, hematological, hepatic and renal parameters, wound healing time, survival and quality of life were all analyzed. Results: The PC index was 2∼33 (median 11), the duration of operation 4∼10 h (median 8 h), and the highest temperature during 5 postoperative d 38.1°C. 2 pts developed systemic edema and were successfully treated, 5 pts developed hypoproteinemia on first postoperative d, all routine blood tests checked at 1 wk postoperatively were normal, time of gastric tube removing was 2∼7 d, liquid food intake time was 3∼8 d, and time of stitches removal was 8∼18 d. There was no infection or disruption of wounds and no intraperitoneal or systemic infections, nor grade 3/4 toxicities in the hematological, hepatic or renal functions. The median follow-up was 8∼26 mon (median 14 mon), with 6 pts died, 8 surviving with tumor, and 7 surviving free of tumor. Conclusions: CRS plus IPHC with MMC 30 and HCPT 20 mg proves to be safe with no serious adverse events; and can prolong the survival and improve the quality of life in selected pts with PC. Suggested doses for phase II study are MMC 30 mg and HCPT 20 mg. No significant financial relationships to disclose.