Timing of adjuvant radioimmunotherapy after cytoreductive surgery in experimental peritoneal carcinomatosis of colorectal origin.
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 mug). 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.


CONCLUSIONS
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.
Aarts
Frits
F
410 Department of Surgery, Radboud University Nijmegen Medical Centre, PO Box 9101, 6500 HB, Nijmegen, The Netherlands. F.Aarts@chir.umcn.nl
Koppe
Manuel J
MJ
Hendriks
Thijs
T
van Eerd
Julliëtte E M
JE
Oyen
Wim J G
WJ
Boerman
Otto C
OC
Bleichrodt
Robert P
RP
D000818:Animals; D015179:Colorectal Neoplasms / Q000473:pathology / Q000532:radiotherapy* / Q000601:surgery; D003131:Combined Modality Therapy; D004195:Disease Models, Animal; D007263:Infusions, Parenteral; D008297:Male; D009374:Neoplasms, Experimental; D010534:Peritoneal Neoplasms / Q000532:radiotherapy* / Q000556:secondary / Q000601:surgery; D010537:Peritoneum; D016499:Radioimmunotherapy; D018714:Radiotherapy, Adjuvant; D051381:Rats; D011919:Rats, Inbred Strains; D013997:Time Factors; D016896:Treatment Outcome