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Original Article |
1 410 Department of Surgery, Radboud University Nijmegen Medical Centre, PO Box 9101, 6500 HB, Nijmegen, The Netherlands
2 444 Department of Nuclear Medicine, Radboud University Nijmegen Medical Centre, PO Box 9101, 6500 HB, Nijmegen, The Netherlands
Correspondence: Address correspondence and reprint requests to: Frits Aarts, MD; E-mail: F.Aarts{at}chir.umcn.nl
Background: Treatment of patients with peritoneal carcinomatosis (PC) of colorectal cancer (CRC) includes cytoreductive surgery (CS) in combination with (hyperthermic) intraperitoneal chemotherapy (HIPEC), resulting in a limited survival benefit with high morbidity and mortality rates. Radioimmunotherapy (RIT) as adjuvant therapy after CS of CRC has been shown to prolong survival in preclinical studies. However, the optimal setting of RIT remains to be determined.
Methods: PC was induced by intraperitoneal inoculation of CC-531 colon carcinoma cells in Wag/Rij rats. Animals were subjected to exploratory laparotomy (Sham), CS only or CS + RIT at different time points after surgery. RIT consisted of 55 MBq lutetium-177-labelled anti-CC531 antibody MG1 (183 µg). The primary endpoint was survival.
Results: Cytoreductive surgery with or without RIT was well tolerated. Median survival of animals in the Sham and CS group was 29 days and 39 days, respectively (P < 0.04). Compared to CS alone, median survival of rats after adjuvant RIT was 77 days (P < 0.0001), 52 days (P < 0.0001) and 45 days (P < 0.0001) when given directly, 4 and 14 days after surgery, respectively.
Conclusion: The efficacy of adjuvant RIT after CS for the treatment of PC of colonic origin decreases when the administration of the radiolabelled MAbs is postponed. This study shows that adjuvant RIT should be given as early as possible after surgery.
Key Words: Radioimmunotherapy • Cytoreductive surgery • Peritoneal carcinomatosis • Colon cancer; adjuvant • Time optimization
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